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Meera Mahalingam - One of the best experts on this subject based on the ideXlab platform.
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an immunohistochemical comparison of Cytokeratin 7 Cytokeratin 15 Cytokeratin 19 cam 5 2 carcinoembryonic antigen and nestin in differentiating porocarcinoma from squamous cell carcinoma
Human Pathology, 2012Co-Authors: Meera Mahalingam, Joanna E Richards, Alona Muzikansky, Angelica M Selim, Mai P. HoangAbstract:Summary The distinction of porocarcinoma from squamous cell carcinoma is clinically relevant but can often be a diagnostic dilemma. Current markers reported to be helpful in diagnosing porocarcinoma include carcinoembryonic antigen and Cytokeratin 7; however, their expression has been demonstrated in 30% to 80% and 13% to 22% of squamous cell carcinoma cases, respectively. In this study, we assessed immunohistochemical expression of Cytokeratin 7, Cytokeratin 15, Cytokeratin 19, CAM 5.2, carcinoembryonic antigen, and nestin in 67 cases (39 porocarcinomas and 28 moderately differentiated squamous cell carcinomas) to determine their use as histologic adjuncts. Expression of carcinoembryonic antigen, Cytokeratin 19, Cytokeratin 7, CAM 5.2, Cytokeratin 15, and nestin was seen in 77%, 67%, 64%, 51%, 49%, and 13% of porocarcinomas, respectively; and in 57%, 18%, 26%, 32%, 30%, and 37% of squamous cell carcinomas, respectively. Of these, Cytokeratin 19 was the most specific (specificity, 82%) in detecting porocarcinomas, and carcinoembryonic antigen was the most sensitive (sensitivity, 77%). By χ 2 test, statistically significant P values ( P = .0003). In conclusion, we found Cytokeratin 19 to be a helpful marker in the distinction of porocarcinoma from squamous cell carcinoma, although a focal staining pattern can be seen in a third of cases. The diagnostic sensitivity and specificity appear to be significantly improved using a selected panel of immunohistochemical stains that include Cytokeratin 7, Cytokeratin 19, and nestin.
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an immunohistochemical comparison of Cytokeratin 7 Cytokeratin 15 Cytokeratin 19 cam 5 2 carcinoembryonic antigen and nestin in differentiating porocarcinoma from squamous cell carcinoma
Human Pathology, 2012Co-Authors: Meera Mahalingam, Joanna E Richards, Alona Muzikansky, Angelica M Selim, Mai P. HoangAbstract:Summary The distinction of porocarcinoma from squamous cell carcinoma is clinically relevant but can often be a diagnostic dilemma. Current markers reported to be helpful in diagnosing porocarcinoma include carcinoembryonic antigen and Cytokeratin 7; however, their expression has been demonstrated in 30% to 80% and 13% to 22% of squamous cell carcinoma cases, respectively. In this study, we assessed immunohistochemical expression of Cytokeratin 7, Cytokeratin 15, Cytokeratin 19, CAM 5.2, carcinoembryonic antigen, and nestin in 67 cases (39 porocarcinomas and 28 moderately differentiated squamous cell carcinomas) to determine their use as histologic adjuncts. Expression of carcinoembryonic antigen, Cytokeratin 19, Cytokeratin 7, CAM 5.2, Cytokeratin 15, and nestin was seen in 77%, 67%, 64%, 51%, 49%, and 13% of porocarcinomas, respectively; and in 57%, 18%, 26%, 32%, 30%, and 37% of squamous cell carcinomas, respectively. Of these, Cytokeratin 19 was the most specific (specificity, 82%) in detecting porocarcinomas, and carcinoembryonic antigen was the most sensitive (sensitivity, 77%). By χ 2 test, statistically significant P values ( P = .0003). In conclusion, we found Cytokeratin 19 to be a helpful marker in the distinction of porocarcinoma from squamous cell carcinoma, although a focal staining pattern can be seen in a third of cases. The diagnostic sensitivity and specificity appear to be significantly improved using a selected panel of immunohistochemical stains that include Cytokeratin 7, Cytokeratin 19, and nestin.
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Stem cell markers (Cytokeratin 15, Cytokeratin 19 and p63) in in situ and invasive cutaneous epithelial lesions
Modern Pathology, 2011Co-Authors: Ossama Abbas, Joanna E Richards, Ron Yaar, Meera MahalingamAbstract:The inherent longetivity of stem cells causes them to be susceptible to multiple genetic hits. Thus, it is not surprising that stem cells are implicated in the etiopathogenesis of select cutaneous neoplasms. However, most studies to date are restricted to the use of a single marker (p63, Cytokeratin-15 or Cytokeratin-19) and do not appear to compare distribution of stem cell markers in a spectrum of cutaneous in situ versus invasive epithelial malignancies. In this study, we evaluate expression of Cytokeratin-15, Cytokeratin-19, and p63 in a series of primary cutaneous epithelial lesions that include actinic keratosis ( n =29), squamous cell carcinoma in situ ( n =30), bowenoid papulosis ( n =15) and squamous cell carcinoma, well differentiated ( n =29) in order to evaluate the role of stem cell marker expression in the grading and development of in situ and invasive malignancies. For Cytokeratin-15, expression was retained in actinic keratosis (38%), squamous cell carcinoma in situ (53%) and bowenoid papulosis (60%) but appeared to be lost in squamous cell carcinoma (3%) with statistically significant differences observed between groups that retained versus those that did not ( P
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stem cell markers Cytokeratin 15 Cytokeratin 19 and p63 in in situ and invasive cutaneous epithelial lesions
Modern Pathology, 2011Co-Authors: Ossama Abbas, Joanna E Richards, Ron Yaar, Meera MahalingamAbstract:The inherent longetivity of stem cells causes them to be susceptible to multiple genetic hits. Thus, it is not surprising that stem cells are implicated in the etiopathogenesis of select cutaneous neoplasms. However, most studies to date are restricted to the use of a single marker (p63, Cytokeratin-15 or Cytokeratin-19) and do not appear to compare distribution of stem cell markers in a spectrum of cutaneous in situ versus invasive epithelial malignancies. In this study, we evaluate expression of Cytokeratin-15, Cytokeratin-19, and p63 in a series of primary cutaneous epithelial lesions that include actinic keratosis (n=29), squamous cell carcinoma in situ (n=30), bowenoid papulosis (n=15) and squamous cell carcinoma, well differentiated (n=29) in order to evaluate the role of stem cell marker expression in the grading and development of in situ and invasive malignancies. For Cytokeratin-15, expression was retained in actinic keratosis (38%), squamous cell carcinoma in situ (53%) and bowenoid papulosis (60%) but appeared to be lost in squamous cell carcinoma (3%) with statistically significant differences observed between groups that retained versus those that did not (P<0.05 for all three); for Cytokeratin-19, patchy yet basal expression was noted in actinic keratosis (21%), patchy and suprabasal expression was noted in squamous cell carcinoma in situ (37%), bowenoid papulosis (13%) and squamous cell carcinoma (24%) with no statistically significant differences between groups; for p63, expression was retained in actinic keratosis (90%), squamous cell carcinoma in situ (87%), bowenoid papulosis (60%) and squamous cell carcinoma (100%) with no statistically significant differences between groups. In summary, our findings expand the neoplasms which involve stem cells to include cutaneous epithelial malignancies. Differential localization of each of these markers argues in favor of stem cell heterogeneity.
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the diagnostic utility of immunohistochemistry in distinguishing primary skin adnexal carcinomas from metastatic adenocarcinoma to skin an immunohistochemical reappraisal using Cytokeratin 15 nestin p63 d2 40 and calretinin
Modern Pathology, 2010Co-Authors: Meera Mahalingam, Joanna E Richards, Alona Muzikansky, Lisa P Nguyen, Mai P. HoangAbstract:Often the distinction of primary adnexal carcinoma from metastatic adenocarcinoma to skin from breast, lung, and other sites can be a diagnostic dilemma. Current markers purportedly of utility as diagnostic adjuncts include p63 and D2-40; however, their expression has been demonstrated in 11–22% and 5% of metastatic cutaneous metastases, respectively. Both Cytokeratin (CK) 15 and nestin have been reported as follicular stem cell markers. We performed CK15 and nestin, as well as previously reported stains (such as p63, D2-40, and calretinin) on 113 cases (59 primary adnexal carcinomas and 54 cutaneous metastases). Expressions of p63, CK15, nestin, D2-40, and calretinin were observed in 91, 40, 37, 44, and 14% of primary adnexal carcinoma, respectively, and in 8, 2, 8, 4, and 10% of cutaneous metastases, respectively. p63 appeared to be the most sensitive marker (with a sensitivity of 91%) in detecting primary adnexal carcinomas. CK15 appeared to be the most specific marker with a specificity of 98%. Using χ2 analysis, statistically significant P-values (<0.05) were observed for p63, CK15, nestin, and D2-40 in the distinction of primary adnexal carcinoma versus cutaneous metastases. In logistic regression and stepwise selection for predicting a primary adnexal carcinoma, statistical significance was observed for p63, CK15, and D2-40 (P-values: <0.001, 0.0275, and 0.0298, respectively) but not for nestin (P-value=0.4573). Our study indicates that diagnostic sensitivity and specificity are significantly improved using a selected panel of immunohistochemical markers, including p63, CK15, and D2-40. Positive staining with all three markers argues in favor of a primary cutaneous adnexal neoplasm.
George F. Murphy - One of the best experts on this subject based on the ideXlab platform.
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differential distribution of the epigenetic marker 5 hydroxymethylcytosine occurs in hair follicle stem cells during bulge activation
Journal of Cutaneous Pathology, 2019Co-Authors: George F. Murphy, Danielle Leavitt, Michael J Wells, Phammela Abarzua, Christine G LianAbstract:Background Hair follicle (HF) cycling is dependent upon activation and differentiation of an epithelial subpopulation of cells with stem-like characteristics. These cells express Cytokeratin 15 (CK15) and are sequestered within a specialized niche termed the follicular bulge. The pathways that mediate bulge activation are poorly understood, although growing evidence suggests a role for epigenetic events. Methods Here we investigated murine and human HFs to determine whether a recently described epigenetic hydroxymethylation marker, 5-hmC, known to mediate cell growth and differentiation, may play a role in bulge activation. Results We found the bulge region of murine HFs to show variable 5-hmC distribution within the nuclei of CK15-positive stem cells during early anagen, a pattern that was not associated with resting stem cells of telogen follicles, which did not express 5-hmC. Moreover, during phases of early anagen that were induced in an organ culture model, spatial alterations in bulge stem cell 5-hmC reactivity, as assessed by dual labeling, were noted. Conclusions These preliminary findings suggest that 5-hmC may play a dynamic role in bulge activation during anagen growth, and provide a foundation for further experimental inquiry into epigenomic regulation of HF stem cells.
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Cutaneous Squamous Cell Carcinomas of the Lower Extremities Show Distinct Clinical and Pathologic Features
International journal of surgical pathology, 2015Co-Authors: Jason F. Solus, George F. Murphy, Stefan KraftAbstract:Cutaneous squamous cell carcinomas mainly affect older, predominantly male patients. Most are due to chronic ultraviolet exposure, and associated with actinic keratoses. On the lower extremities, they occur more commonly in women. However, data on these tumors as a distinct group are scarce. We evaluated 61 squamous cell carcinomas of the lower extremities. Overall, 69% of patients were female. Mean age was 75 years. More than 90% of tumors were well differentiated, 3% showed perineural invasion, and none lymphovascular invasion. In all, 63.9% showed evidence of severe chronic sun damage. Associated actinic keratoses were identified in only 13% of cases. By contrast, 80% were associated with distinctive basal epidermal proliferations with a retiform growth pattern. These proliferations were evaluated immunohistochemically for keratinocyte stem cell markers, p53 and Notch1 in 15 cases. All cases were positive for Cytokeratin 14, p53, and Notch1 (with variable intensity in the latter 2), and predominantly negative for Cytokeratin 19. Interestingly, basal retiform proliferations were positive for Cytokeratin 15 in 66% of cases. Fifteen head and neck squamous cell carcinomas were evaluated in comparison. Those lacked associated basal retiform proliferations except in 1 case. In contrast, 87% were associated with actinic keratoses and 100% with severe chronic sun damage. Actinic keratoses associated with head and neck tumors showed Cytokeratin 15 staining only in 7% of cases (P = .003 compared with Cytokeratin 15 in basal retiform proliferations associated with leg carcinomas). These findings support the hypothesis that lower extremity squamous cell carcinomas are distinct and may exhibit a pathogenesis less reliant on actinic damage.
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graft versus host disease related cytokine driven apoptosis depends on p73 in Cytokeratin 15 positive target cells
Biology of Blood and Marrow Transplantation, 2012Co-Authors: Qian Zhan, Robert Korngold, Cecilia Lezcano, Frank Mckeon, George F. MurphyAbstract:Acute graft-versus-host disease (GVHD), a major complication of allogeneic stem cell transplantation, involves cytotoxic soluble and cellular effectors that selectively induce apoptosis in normally apoptosis-resistant, Cytokeratin 15 (K15)-expressing epithelial stem cells residing at the tips of rete ridges of human epidermis and in analogous rete-like prominences (RLPs) of murine dorsal lingual epithelium. The mechanisms whereby epithelial stem cells are rendered vulnerable to apoptosis during allostimulation are unknown. We hypothesized that GVHD-induced target cell injury may be related to pathways involving the p53 family that are constitutively expressed by epithelial stem cells and designed to trigger physiological apoptosis as a result of environmental danger signals. Among the p53 family members, we found that p73 protein and mRNA were preferentially expressed in K15+ RLPs of murine lingual squamous epithelium. On in vitro exposure to recombinant TNF-α and IL-1 in an organ culture model previously shown to replicate early GVHD-like target cell injury, apoptosis was selectively induced in K15+ stem cell regions and was associated with induction of phosphorylated p73, a marker for p73 activation, and apoptosis was abrogated in target tissue obtained from p73-deficient (p73−/−) mice. Evaluation of early in vivo lesions in experimental murine GVHD disclosed identical patterns of phosphorylated p73 expression that coincided with the onset of effector T cell infiltration and target cell apoptosis within K15+ RLPs. This study is the first to suggest that paradoxical apoptosis in GVHD of physiologically protected K15+ epithelial stem cells is explainable, at least in part, by cytokine-induced activation of suicide pathways designed to eliminate stem cells after exposure to deleterious factors perceived to be harmful to the host.
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Graft-versus-Host Disease–Related Cytokine-Driven Apoptosis Depends on p73 in Cytokeratin 15–Positive Target Cells
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2012Co-Authors: Qian Zhan, Robert Korngold, Cecilia Lezcano, Frank Mckeon, George F. MurphyAbstract:Acute graft-versus-host disease (GVHD), a major complication of allogeneic stem cell transplantation, involves cytotoxic soluble and cellular effectors that selectively induce apoptosis in normally apoptosis-resistant, Cytokeratin 15 (K15)-expressing epithelial stem cells residing at the tips of rete ridges of human epidermis and in analogous rete-like prominences (RLPs) of murine dorsal lingual epithelium. The mechanisms whereby epithelial stem cells are rendered vulnerable to apoptosis during allostimulation are unknown. We hypothesized that GVHD-induced target cell injury may be related to pathways involving the p53 family that are constitutively expressed by epithelial stem cells and designed to trigger physiological apoptosis as a result of environmental danger signals. Among the p53 family members, we found that p73 protein and mRNA were preferentially expressed in K15+ RLPs of murine lingual squamous epithelium. On in vitro exposure to recombinant TNF-α and IL-1 in an organ culture model previously shown to replicate early GVHD-like target cell injury, apoptosis was selectively induced in K15+ stem cell regions and was associated with induction of phosphorylated p73, a marker for p73 activation, and apoptosis was abrogated in target tissue obtained from p73-deficient (p73−/−) mice. Evaluation of early in vivo lesions in experimental murine GVHD disclosed identical patterns of phosphorylated p73 expression that coincided with the onset of effector T cell infiltration and target cell apoptosis within K15+ RLPs. This study is the first to suggest that paradoxical apoptosis in GVHD of physiologically protected K15+ epithelial stem cells is explainable, at least in part, by cytokine-induced activation of suicide pathways designed to eliminate stem cells after exposure to deleterious factors perceived to be harmful to the host.
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Target Cells in Graft-Versus-Host Disease: Implications for Cancer Therapy
Clinical Reviews in Allergy & Immunology, 2007Co-Authors: George F. MurphyAbstract:Acute graft-versus-host disease (GVHD) conceptually may be divided into three evolutionary stages: allostimulation, effector cell homing to specific tissues, and cellular targeting and injury. Surprisingly, little is known regarding the targeting stage of GVHD. Recently, we have learned that epithelial target cell injury is mediated by specific subpopulations of effector T cells that may be identified based on Vβ family expansion during allostimulation. Antibody probes specific for these Vβ families have permitted precise identification of effector cell homing patterns. In squamous epithelium, allospecific T cells selectively home to basal cell layer subpopulations that express Cytokeratin 15 (CK15) and that undergo target cell injury via apoptosis. Interestingly, these target cells coincide with basal layer subpopulations that have properties of epithelial stem cells and that normally express an apoptosis-resistant genomic profile. Accordingly, epithelial cell injury in GVHD appears to involve selective targeting of stem-cell subpopulations via conversion from an anti-apoptotic to a pro-apoptotic phenotype. Understanding of the mechanism(s) of this conversion could facilitate development of translationally relevant approaches to shielding target cells from injury in GVHD. Moreover, determination of how putative apoptosis-resistant stem cells may be rendered vulnerable to immune-mediated targeting has implications potentially relevant to more directed immunotherapeutic approaches focused at elimination of neoplastic (cancer) stem cells.
Mai P. Hoang - One of the best experts on this subject based on the ideXlab platform.
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an immunohistochemical comparison of Cytokeratin 7 Cytokeratin 15 Cytokeratin 19 cam 5 2 carcinoembryonic antigen and nestin in differentiating porocarcinoma from squamous cell carcinoma
Human Pathology, 2012Co-Authors: Meera Mahalingam, Joanna E Richards, Alona Muzikansky, Angelica M Selim, Mai P. HoangAbstract:Summary The distinction of porocarcinoma from squamous cell carcinoma is clinically relevant but can often be a diagnostic dilemma. Current markers reported to be helpful in diagnosing porocarcinoma include carcinoembryonic antigen and Cytokeratin 7; however, their expression has been demonstrated in 30% to 80% and 13% to 22% of squamous cell carcinoma cases, respectively. In this study, we assessed immunohistochemical expression of Cytokeratin 7, Cytokeratin 15, Cytokeratin 19, CAM 5.2, carcinoembryonic antigen, and nestin in 67 cases (39 porocarcinomas and 28 moderately differentiated squamous cell carcinomas) to determine their use as histologic adjuncts. Expression of carcinoembryonic antigen, Cytokeratin 19, Cytokeratin 7, CAM 5.2, Cytokeratin 15, and nestin was seen in 77%, 67%, 64%, 51%, 49%, and 13% of porocarcinomas, respectively; and in 57%, 18%, 26%, 32%, 30%, and 37% of squamous cell carcinomas, respectively. Of these, Cytokeratin 19 was the most specific (specificity, 82%) in detecting porocarcinomas, and carcinoembryonic antigen was the most sensitive (sensitivity, 77%). By χ 2 test, statistically significant P values ( P = .0003). In conclusion, we found Cytokeratin 19 to be a helpful marker in the distinction of porocarcinoma from squamous cell carcinoma, although a focal staining pattern can be seen in a third of cases. The diagnostic sensitivity and specificity appear to be significantly improved using a selected panel of immunohistochemical stains that include Cytokeratin 7, Cytokeratin 19, and nestin.
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an immunohistochemical comparison of Cytokeratin 7 Cytokeratin 15 Cytokeratin 19 cam 5 2 carcinoembryonic antigen and nestin in differentiating porocarcinoma from squamous cell carcinoma
Human Pathology, 2012Co-Authors: Meera Mahalingam, Joanna E Richards, Alona Muzikansky, Angelica M Selim, Mai P. HoangAbstract:Summary The distinction of porocarcinoma from squamous cell carcinoma is clinically relevant but can often be a diagnostic dilemma. Current markers reported to be helpful in diagnosing porocarcinoma include carcinoembryonic antigen and Cytokeratin 7; however, their expression has been demonstrated in 30% to 80% and 13% to 22% of squamous cell carcinoma cases, respectively. In this study, we assessed immunohistochemical expression of Cytokeratin 7, Cytokeratin 15, Cytokeratin 19, CAM 5.2, carcinoembryonic antigen, and nestin in 67 cases (39 porocarcinomas and 28 moderately differentiated squamous cell carcinomas) to determine their use as histologic adjuncts. Expression of carcinoembryonic antigen, Cytokeratin 19, Cytokeratin 7, CAM 5.2, Cytokeratin 15, and nestin was seen in 77%, 67%, 64%, 51%, 49%, and 13% of porocarcinomas, respectively; and in 57%, 18%, 26%, 32%, 30%, and 37% of squamous cell carcinomas, respectively. Of these, Cytokeratin 19 was the most specific (specificity, 82%) in detecting porocarcinomas, and carcinoembryonic antigen was the most sensitive (sensitivity, 77%). By χ 2 test, statistically significant P values ( P = .0003). In conclusion, we found Cytokeratin 19 to be a helpful marker in the distinction of porocarcinoma from squamous cell carcinoma, although a focal staining pattern can be seen in a third of cases. The diagnostic sensitivity and specificity appear to be significantly improved using a selected panel of immunohistochemical stains that include Cytokeratin 7, Cytokeratin 19, and nestin.
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the diagnostic utility of immunohistochemistry in distinguishing primary skin adnexal carcinomas from metastatic adenocarcinoma to skin an immunohistochemical reappraisal using Cytokeratin 15 nestin p63 d2 40 and calretinin
Modern Pathology, 2010Co-Authors: Meera Mahalingam, Joanna E Richards, Alona Muzikansky, Lisa P Nguyen, Mai P. HoangAbstract:Often the distinction of primary adnexal carcinoma from metastatic adenocarcinoma to skin from breast, lung, and other sites can be a diagnostic dilemma. Current markers purportedly of utility as diagnostic adjuncts include p63 and D2-40; however, their expression has been demonstrated in 11–22% and 5% of metastatic cutaneous metastases, respectively. Both Cytokeratin (CK) 15 and nestin have been reported as follicular stem cell markers. We performed CK15 and nestin, as well as previously reported stains (such as p63, D2-40, and calretinin) on 113 cases (59 primary adnexal carcinomas and 54 cutaneous metastases). Expressions of p63, CK15, nestin, D2-40, and calretinin were observed in 91, 40, 37, 44, and 14% of primary adnexal carcinoma, respectively, and in 8, 2, 8, 4, and 10% of cutaneous metastases, respectively. p63 appeared to be the most sensitive marker (with a sensitivity of 91%) in detecting primary adnexal carcinomas. CK15 appeared to be the most specific marker with a specificity of 98%. Using χ2 analysis, statistically significant P-values (<0.05) were observed for p63, CK15, nestin, and D2-40 in the distinction of primary adnexal carcinoma versus cutaneous metastases. In logistic regression and stepwise selection for predicting a primary adnexal carcinoma, statistical significance was observed for p63, CK15, and D2-40 (P-values: <0.001, 0.0275, and 0.0298, respectively) but not for nestin (P-value=0.4573). Our study indicates that diagnostic sensitivity and specificity are significantly improved using a selected panel of immunohistochemical markers, including p63, CK15, and D2-40. Positive staining with all three markers argues in favor of a primary cutaneous adnexal neoplasm.
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The diagnostic utility of immunohistochemistry in distinguishing primary skin adnexal carcinomas from metastatic adenocarcinoma to skin: an immunohistochemical reappraisal using Cytokeratin 15, nestin, p63, D2-40, and calretinin
Modern Pathology, 2010Co-Authors: Meera Mahalingam, Joanna E Richards, Alona Muzikansky, Lisa P Nguyen, Mai P. HoangAbstract:Often the distinction of primary adnexal carcinoma from metastatic adenocarcinoma to skin from breast, lung, and other sites can be a diagnostic dilemma. Current markers purportedly of utility as diagnostic adjuncts include p63 and D2-40; however, their expression has been demonstrated in 11–22% and 5% of metastatic cutaneous metastases, respectively. Both Cytokeratin (CK) 15 and nestin have been reported as follicular stem cell markers. We performed CK15 and nestin, as well as previously reported stains (such as p63, D2-40, and calretinin) on 113 cases (59 primary adnexal carcinomas and 54 cutaneous metastases). Expressions of p63, CK15, nestin, D2-40, and calretinin were observed in 91, 40, 37, 44, and 14% of primary adnexal carcinoma, respectively, and in 8, 2, 8, 4, and 10% of cutaneous metastases, respectively. p63 appeared to be the most sensitive marker (with a sensitivity of 91%) in detecting primary adnexal carcinomas. CK15 appeared to be the most specific marker with a specificity of 98%. Using χ ^2 analysis, statistically significant P -values (
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Expression of stem-cell markers (Cytokeratin 15 and nestin) in primary adnexal neoplasms-clues to etiopathogenesis.
The American Journal of dermatopathology, 2010Co-Authors: Meera Mahalingam, Anvita Srivastava, Mai P. HoangAbstract:Background: The overlap in histopathologic features and immunoprofile of eccrine and apocrine neoplasms confounds basic issues relating to lineage of these entities. Methods: We evaluated expression of follicular stem-cell markers, Cytokeratin (CK) 15 and nestin, in 78 benign and 23 malignant adnexal neoplasms. Results: CK15 and nestin expression were noted in 39 of 78 (50%) and 36 of 78 (46%) cases in the benign group, respectively (8 cutaneous mixed tumor, 10 hidradenoma papilliferum, 9 apocrine cystadenoma, 11 cylindroma and/or spiradenoma, and 9 poroma/dermal duct tumor). CK15 and nestin expression were noted in 11 of 23 (48%) and 7 of 23 (30%) cases in the malignant group, respectively (6 microcystic adnexal carcinoma, 7 porocarcinoma, and 9 eccrine carcinoma). Except 1, both markers were negative in 4 syringocystadenoma papilliferum, 10 hidradenoma, 1 syringofibroadenoma, 10 syringoma, 1 eccrine adenoma, 8 poroma/dermal duct tumor, 5 eccrine hidrocystoma, and 1 apocrine carcinoma. Conclusions: Given that follicular germinative cells give rise to the folliculosebaceous apocrine unit, expression of CK15 and nestin in the majority of cutaneous mixed tumor, hidradenoma papilliferum, apocrine cystadenoma, and cylindroma/spiradenoma is suggestive of an apocrine origin/differentiation of these neoplasms. Reinforcing this and a novel finding of our study is the preferential expression of nestin in myoepithelial cells of these lesions.
Joanna E Richards - One of the best experts on this subject based on the ideXlab platform.
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an immunohistochemical comparison of Cytokeratin 7 Cytokeratin 15 Cytokeratin 19 cam 5 2 carcinoembryonic antigen and nestin in differentiating porocarcinoma from squamous cell carcinoma
Human Pathology, 2012Co-Authors: Meera Mahalingam, Joanna E Richards, Alona Muzikansky, Angelica M Selim, Mai P. HoangAbstract:Summary The distinction of porocarcinoma from squamous cell carcinoma is clinically relevant but can often be a diagnostic dilemma. Current markers reported to be helpful in diagnosing porocarcinoma include carcinoembryonic antigen and Cytokeratin 7; however, their expression has been demonstrated in 30% to 80% and 13% to 22% of squamous cell carcinoma cases, respectively. In this study, we assessed immunohistochemical expression of Cytokeratin 7, Cytokeratin 15, Cytokeratin 19, CAM 5.2, carcinoembryonic antigen, and nestin in 67 cases (39 porocarcinomas and 28 moderately differentiated squamous cell carcinomas) to determine their use as histologic adjuncts. Expression of carcinoembryonic antigen, Cytokeratin 19, Cytokeratin 7, CAM 5.2, Cytokeratin 15, and nestin was seen in 77%, 67%, 64%, 51%, 49%, and 13% of porocarcinomas, respectively; and in 57%, 18%, 26%, 32%, 30%, and 37% of squamous cell carcinomas, respectively. Of these, Cytokeratin 19 was the most specific (specificity, 82%) in detecting porocarcinomas, and carcinoembryonic antigen was the most sensitive (sensitivity, 77%). By χ 2 test, statistically significant P values ( P = .0003). In conclusion, we found Cytokeratin 19 to be a helpful marker in the distinction of porocarcinoma from squamous cell carcinoma, although a focal staining pattern can be seen in a third of cases. The diagnostic sensitivity and specificity appear to be significantly improved using a selected panel of immunohistochemical stains that include Cytokeratin 7, Cytokeratin 19, and nestin.
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an immunohistochemical comparison of Cytokeratin 7 Cytokeratin 15 Cytokeratin 19 cam 5 2 carcinoembryonic antigen and nestin in differentiating porocarcinoma from squamous cell carcinoma
Human Pathology, 2012Co-Authors: Meera Mahalingam, Joanna E Richards, Alona Muzikansky, Angelica M Selim, Mai P. HoangAbstract:Summary The distinction of porocarcinoma from squamous cell carcinoma is clinically relevant but can often be a diagnostic dilemma. Current markers reported to be helpful in diagnosing porocarcinoma include carcinoembryonic antigen and Cytokeratin 7; however, their expression has been demonstrated in 30% to 80% and 13% to 22% of squamous cell carcinoma cases, respectively. In this study, we assessed immunohistochemical expression of Cytokeratin 7, Cytokeratin 15, Cytokeratin 19, CAM 5.2, carcinoembryonic antigen, and nestin in 67 cases (39 porocarcinomas and 28 moderately differentiated squamous cell carcinomas) to determine their use as histologic adjuncts. Expression of carcinoembryonic antigen, Cytokeratin 19, Cytokeratin 7, CAM 5.2, Cytokeratin 15, and nestin was seen in 77%, 67%, 64%, 51%, 49%, and 13% of porocarcinomas, respectively; and in 57%, 18%, 26%, 32%, 30%, and 37% of squamous cell carcinomas, respectively. Of these, Cytokeratin 19 was the most specific (specificity, 82%) in detecting porocarcinomas, and carcinoembryonic antigen was the most sensitive (sensitivity, 77%). By χ 2 test, statistically significant P values ( P = .0003). In conclusion, we found Cytokeratin 19 to be a helpful marker in the distinction of porocarcinoma from squamous cell carcinoma, although a focal staining pattern can be seen in a third of cases. The diagnostic sensitivity and specificity appear to be significantly improved using a selected panel of immunohistochemical stains that include Cytokeratin 7, Cytokeratin 19, and nestin.
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Stem cell markers (Cytokeratin 15, Cytokeratin 19 and p63) in in situ and invasive cutaneous epithelial lesions
Modern Pathology, 2011Co-Authors: Ossama Abbas, Joanna E Richards, Ron Yaar, Meera MahalingamAbstract:The inherent longetivity of stem cells causes them to be susceptible to multiple genetic hits. Thus, it is not surprising that stem cells are implicated in the etiopathogenesis of select cutaneous neoplasms. However, most studies to date are restricted to the use of a single marker (p63, Cytokeratin-15 or Cytokeratin-19) and do not appear to compare distribution of stem cell markers in a spectrum of cutaneous in situ versus invasive epithelial malignancies. In this study, we evaluate expression of Cytokeratin-15, Cytokeratin-19, and p63 in a series of primary cutaneous epithelial lesions that include actinic keratosis ( n =29), squamous cell carcinoma in situ ( n =30), bowenoid papulosis ( n =15) and squamous cell carcinoma, well differentiated ( n =29) in order to evaluate the role of stem cell marker expression in the grading and development of in situ and invasive malignancies. For Cytokeratin-15, expression was retained in actinic keratosis (38%), squamous cell carcinoma in situ (53%) and bowenoid papulosis (60%) but appeared to be lost in squamous cell carcinoma (3%) with statistically significant differences observed between groups that retained versus those that did not ( P
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stem cell markers Cytokeratin 15 Cytokeratin 19 and p63 in in situ and invasive cutaneous epithelial lesions
Modern Pathology, 2011Co-Authors: Ossama Abbas, Joanna E Richards, Ron Yaar, Meera MahalingamAbstract:The inherent longetivity of stem cells causes them to be susceptible to multiple genetic hits. Thus, it is not surprising that stem cells are implicated in the etiopathogenesis of select cutaneous neoplasms. However, most studies to date are restricted to the use of a single marker (p63, Cytokeratin-15 or Cytokeratin-19) and do not appear to compare distribution of stem cell markers in a spectrum of cutaneous in situ versus invasive epithelial malignancies. In this study, we evaluate expression of Cytokeratin-15, Cytokeratin-19, and p63 in a series of primary cutaneous epithelial lesions that include actinic keratosis (n=29), squamous cell carcinoma in situ (n=30), bowenoid papulosis (n=15) and squamous cell carcinoma, well differentiated (n=29) in order to evaluate the role of stem cell marker expression in the grading and development of in situ and invasive malignancies. For Cytokeratin-15, expression was retained in actinic keratosis (38%), squamous cell carcinoma in situ (53%) and bowenoid papulosis (60%) but appeared to be lost in squamous cell carcinoma (3%) with statistically significant differences observed between groups that retained versus those that did not (P<0.05 for all three); for Cytokeratin-19, patchy yet basal expression was noted in actinic keratosis (21%), patchy and suprabasal expression was noted in squamous cell carcinoma in situ (37%), bowenoid papulosis (13%) and squamous cell carcinoma (24%) with no statistically significant differences between groups; for p63, expression was retained in actinic keratosis (90%), squamous cell carcinoma in situ (87%), bowenoid papulosis (60%) and squamous cell carcinoma (100%) with no statistically significant differences between groups. In summary, our findings expand the neoplasms which involve stem cells to include cutaneous epithelial malignancies. Differential localization of each of these markers argues in favor of stem cell heterogeneity.
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the diagnostic utility of immunohistochemistry in distinguishing primary skin adnexal carcinomas from metastatic adenocarcinoma to skin an immunohistochemical reappraisal using Cytokeratin 15 nestin p63 d2 40 and calretinin
Modern Pathology, 2010Co-Authors: Meera Mahalingam, Joanna E Richards, Alona Muzikansky, Lisa P Nguyen, Mai P. HoangAbstract:Often the distinction of primary adnexal carcinoma from metastatic adenocarcinoma to skin from breast, lung, and other sites can be a diagnostic dilemma. Current markers purportedly of utility as diagnostic adjuncts include p63 and D2-40; however, their expression has been demonstrated in 11–22% and 5% of metastatic cutaneous metastases, respectively. Both Cytokeratin (CK) 15 and nestin have been reported as follicular stem cell markers. We performed CK15 and nestin, as well as previously reported stains (such as p63, D2-40, and calretinin) on 113 cases (59 primary adnexal carcinomas and 54 cutaneous metastases). Expressions of p63, CK15, nestin, D2-40, and calretinin were observed in 91, 40, 37, 44, and 14% of primary adnexal carcinoma, respectively, and in 8, 2, 8, 4, and 10% of cutaneous metastases, respectively. p63 appeared to be the most sensitive marker (with a sensitivity of 91%) in detecting primary adnexal carcinomas. CK15 appeared to be the most specific marker with a specificity of 98%. Using χ2 analysis, statistically significant P-values (<0.05) were observed for p63, CK15, nestin, and D2-40 in the distinction of primary adnexal carcinoma versus cutaneous metastases. In logistic regression and stepwise selection for predicting a primary adnexal carcinoma, statistical significance was observed for p63, CK15, and D2-40 (P-values: <0.001, 0.0275, and 0.0298, respectively) but not for nestin (P-value=0.4573). Our study indicates that diagnostic sensitivity and specificity are significantly improved using a selected panel of immunohistochemical markers, including p63, CK15, and D2-40. Positive staining with all three markers argues in favor of a primary cutaneous adnexal neoplasm.
Kazuo Tsubota - One of the best experts on this subject based on the ideXlab platform.
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a novel nih 3t3 duplex feeder system to engineer corneal epithelial sheets with enhanced Cytokeratin 15 positive progenitor populations
Tissue Engineering Part A, 2008Co-Authors: Hideyuki Miyashita, Tetsuya Kawakita, Shigeto Shimmura, Jun Shimazaki, Kazunari Higa, S Yoshida, Kazuo TsubotaAbstract:Corneal epithelial cell sheets co-cultivated with feeder cells are used to reconstruct the ocular surface in stem cell–depleted eyes. The present study was conducted to investigate the optimal method of using feeder cells in the interest of preserving progenitor cells in cultivated sheets. We compared the phenotype and secondary colony forming efficiency (CFE) of cell sheets that were engineered using 3T3 feeder cells as a separate layer or as a contact layer. We also devised a novel “duplex feeder” system that consists of two separate layers of feeder cells. After cells reached confluence, cells were cultured at the air–liquid interface to allow full stratification. Stratified sheets were then analyzed using immunohistochemistry and secondary colony formation. Contact feeder cultures and duplex feeder cultures yielded epithelial sheets with small, cuboid basal cells with strong expression of keratin (K)3, K12, and K15. Furthermore, only duplex feeder layers reproduced the basal K15, suprabasal K12 limbal...
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a novel nih 3t3 duplex feeder system to engineer corneal epithelial sheets with enhanced Cytokeratin 15 positive progenitor populations
Tissue Engineering Part A, 2008Co-Authors: Hideyuki Miyashita, Tetsuya Kawakita, Satoru Yoshida, Shigeto Shimmura, Jun Shimazaki, Kazuo Tsubota, Kazunari HigaAbstract:Corneal epithelial cell sheets co-cultivated with feeder cells are used to reconstruct the ocular surface in stem cell–depleted eyes. The present study was conducted to investigate the optimal meth...
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A novel NIH/3T3 duplex feeder system to engineer corneal epithelial sheets with enhanced Cytokeratin 15-positive progenitor populations.
Tissue engineering. Part A, 2008Co-Authors: Hideyuki Miyashita, Tetsuya Kawakita, Satoru Yoshida, Shigeto Shimmura, Jun Shimazaki, Kazunari Higa, Kazuo TsubotaAbstract:Corneal epithelial cell sheets co-cultivated with feeder cells are used to reconstruct the ocular surface in stem cell–depleted eyes. The present study was conducted to investigate the optimal meth...
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Cytokeratin 15 can be used to identify the limbal phenotype in normal and diseased ocular surfaces.
Investigative ophthalmology & visual science, 2006Co-Authors: Satoru Yoshida, Tetsuya Kawakita, Shigeto Shimmura, Hideyuki Miyashita, Seika Den, Jun Shimazaki, Kazuo TsubotaAbstract:Purpose To elucidate the expression pattern of K15, K19, K14, and K12 in human and mouse ocular surface epithelium as putative markers of epithelial phenotype. Methods Immunohistochemical staining with specific antibodies for K15, K19, K14, and K12 was performed in human donor cornea tissue and normal ICR mouse corneas, with emphasis on localization of immunopositive cells. Immunohistochemistry was performed in a limbus-deficient mouse model as well as in clinical samples of pannus surgically removed from a thermal burn and a patient with Saltzmann's dystrophy. Staining patterns were classified as limited to the most basal layer (K(bas)), basal and suprabasal layers (K(bas-sup)), predominantly in suprabasal layers (K(sup)) and negative staining (K(-)). Results In human conjunctival epithelium, strong expression of K15 was observed in basal cells, whereas K19 was expressed in both basal and suprabasal layers (K15(bas)/K19(bas-sup)/K12(-)). Limbal epithelial cells were K15(bas-sup)/K19(bas-sup)/K12(sup), whereas epithelial cells in the central cornea were K15(-)/K19(bas-sup)/K12(bas-sup). In contrast, the mouse ocular surface demonstrated a different expression pattern of K15 and K19 than did the human tissue in the conjunctiva (K15(bas-sup)/K19(bas)/K12(-)) and the limbus (K15(bas-sup)/K19(bas)/K12(sup)). Neither K15 nor K19 was expressed in the central mouse cornea (K15(-)/K19(-)/K12(bas-sup)). Similar Cytokeratin expression was observed in conjunctivalized corneas in mice and in surgically removed pannus tissue. Conclusions Although the expression of K15 and K19 differ in humans and mice, specific staining patterns can be used to characterize the epithelial phenotype in normal and diseased ocular surface.
