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Jonathan I Epstein - One of the best experts on this subject based on the ideXlab platform.
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prostate cancer grading a decade after the 2005 modified gleason grading system
Archives of Pathology & Laboratory Medicine, 2016Co-Authors: Oleksandr N Kryvenko, Jonathan I EpsteinAbstract:Since 1966, when Donald Gleason, MD, first proposed grading prostate cancer based on its histologic architecture, there have been numerous changes in clinical and pathologic practices relating to prostate cancer. Patterns 1 and 2, comprising more than 30% of cases in the original publications by Gleason, are no longer reported on biopsy and are rarely diagnosed on radical prostatectomy. Many of these cases may even have been mimickers of prostate cancer that were described later with the use of contemporary immunohistochemistry. The original Gleason system predated many newly described variants of prostate cancer and our current concept of Intraductal Carcinoma. Gleason also did not describe how to report prostate cancer on biopsy with multiple cores of cancer or on radical prostatectomy with separate tumor nodules. To address these issues, the International Society of Urological Pathology first made revisions to the grading system in 2005, and subsequently in 2014. Additionally, a new grading system comp...
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cytoplasmic pten protein loss distinguishes Intraductal Carcinoma of the prostate from high grade prostatic intraepithelial neoplasia
Modern Pathology, 2013Co-Authors: Tamara L Lotan, Berrak Gumuskaya, Hameed Rahimi, Jessica Hicks, Tsuyoshi Iwata, Brian D Robinson, Jonathan I Epstein, Angelo M De MarzoAbstract:Cytoplasmic PTEN protein loss distinguishes Intraductal Carcinoma of the prostate from high-grade prostatic intraepithelial neoplasia
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cytoplasmic pten protein loss distinguishes Intraductal Carcinoma of the prostate from high grade prostatic intraepithelial neoplasia
Modern Pathology, 2013Co-Authors: Tamara L Lotan, Berrak Gumuskaya, Hameed Rahimi, Jessica Hicks, Tsuyoshi Iwata, Brian D Robinson, Jonathan I Epstein, Angelo M De MarzoAbstract:Intraductal Carcinoma of the prostate is a marker of aggressive disease. However, Intraductal Carcinoma exists on a morphologic continuum with high-grade prostatic intraepithelial neoplasia (PIN) and distinguishing Intraductal Carcinoma from PIN is a common diagnostic dilemma with significant clinical implications. We evaluated whether immunostains for PTEN and ERG can sensitively identify Intraductal Carcinoma and accurately distinguish it from high-grade PIN. A combined immunostain for PTEN, ERG, p63 and CK903 was developed and validated. Radical prostatectomy specimens with lesions meeting criteria for Intraductal Carcinoma (n=45), Intraductal cribriform proliferations falling short of Intraductal Carcinoma (n=15), and PIN lesions (n=39) were retrospectively identified and assessed for PTEN and ERG. Cytoplasmic PTEN loss was identified in 84% (38/45) of the Intraductal Carcinoma and 100% (15/15) of Intraductal cribriform proliferation cases. In contrast, cytoplasmic PTEN loss was never observed in PIN (0/39; P 95% and P<0.0001 for each), and substantially less for PIN and the concurrent invasive tumor (83% for PTEN and 67% for ERG; P=NS for each). Cytoplasmic PTEN loss occurs in the majority of Intraductal Carcinoma and Intraductal cribriform proliferation cases. Cytoplasmic PTEN loss was never observed in PIN (100% specificity). Our study identifies PTEN loss as a potentially useful marker to distinguish Intraductal Carcinoma from PIN and provides a plausible molecular explanation for why Intraductal Carcinoma is associated with poor prognosis.
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Intraductal Carcinoma of the prostate without invasive Carcinoma on needle biopsy emphasis on radical prostatectomy findings
The Journal of Urology, 2010Co-Authors: Brian D Robinson, Jonathan I EpsteinAbstract:Purpose: Limited information is available on radical prostatectomy findings in men with Intraductal Carcinoma of the prostate on needle core biopsy in the absence of invasive prostate cancer.Materials and Methods: From the consulting files of one of us we identified 83 men in whom biopsy showed only Intraductal prostate cancer. Followup was available in 66 cases. We reviewed slides in 21 radical prostatectomy cases.Results: Treatment was radical prostatectomy in 23 men, radiation therapy in 15, hormone therapy in 8 and radiation plus hormone therapy in 15 while 5 underwent no treatment or repeat biopsy. Of the 21 radical prostatectomies available for review findings revealed pathological stage pT3a in 8 (38%), pT3b in 3 (13%), pT2 in 8 (38%) and Intraductal Carcinoma without identifiable invasive cancer in 2 (10%). One patient with pT3a had a positive lymph node at surgery. Average Gleason score was 7.9. Three patients (14%) experienced post-prostatectomy biochemical failure and another (5%) had bone meta...
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Intraductal Carcinoma of the prostate on needle biopsy: histologic features and clinical significance
Modern Pathology, 2006Co-Authors: Jonathan I EpsteinAbstract:Intraductal Carcinoma of the prostate (IDC-P) has been described in radical prostatectomies. However, there is limited information as to its histologic features and clinical significance when seen on prostate biopsy. A total of 27 cases of prostate biopsies with only IDC-P (ie no infiltrating cancer anywhere on the biopsy) were studied from the consult files of one of the authors. IDC-P was defined as malignant epithelial cells filling large acini and prostatic ducts, with preservation of basal cells forming either: (1) solid or dense cribriform patterns or; (2) loose cribriform or micropapillary patterns with either marked nuclear atypia (nuclear size 6 × normal or larger) or comedonecrosis. The numbers of cores involved by IDC-P in the biopsies ranged from 1 to 7, with >1 core involved in 17 cases. The architectural patterns of IDC-P were solid (12), dense cribriform (19), loose cribriform (17), and micropapillary (5). More than one pattern was present in 24 of 27 cases. The cytological features frequently observed in IDC-P were marked pleomorphism (18), non-focal comedonecrosis (22), and mitoses (20). Basal cells were observed on regular hematoxylin and eosin stained slides in 14 cases; in all the cases, basal cells were confirmed by immunohistochemical stains for high molecular weight cytokeratin ( n =25) and/or p63 ( n =4). After the diagnosis of IDC-P on prostate biopsies, patients were treated by radical prostatectomy (6), radiation (7), hormone (5), combined radiation and hormone (1), or watchful waiting (2). The follow-up information was not available for six patients. The follow-up times ranged up to 4 years with an average of 2.1 years. In all six radical prostatectomy specimens, high-grade infiltrating Carcinoma with Gleason score 8 or 9 was present with five cases also revealing prominent IDC-P. Non-focal extraprostatic extension of Carcinoma was observed in five of the six prostatectomy cases with two cases also demonstrating vascular invasion. Three of 16 patients who did not receive radical prostatectomy developed bone metastases. Our study indicates that IDC-P on prostate biopsies is frequently associated with high-grade cancer and poor prognostic parameters at radical prostatectomy as well as potentially advanced disease following other therapies. These findings support prior studies that IDC-P represents an advanced stage of tumor progression with Intraductal spread of tumor. Consideration should be given to treat patients with IDC-P on biopsy aggressively even in the absence of documented infiltrating cancer.
Angelo M De Marzo - One of the best experts on this subject based on the ideXlab platform.
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utility of pten and erg immunostaining for distinguishing high grade pin from Intraductal Carcinoma of the prostate on needle biopsy
The American Journal of Surgical Pathology, 2015Co-Authors: Carlos L Morais, Rajal B Shah, Cristina Magigalluzzi, Ming Zhou, Jessica Hicks, Jennifer Gordetsky, Ann E Anderson, Jonathan I Epstein, Michael Nagar, Angelo M De MarzoAbstract:Intraductal Carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to
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cytoplasmic pten protein loss distinguishes Intraductal Carcinoma of the prostate from high grade prostatic intraepithelial neoplasia
Modern Pathology, 2013Co-Authors: Tamara L Lotan, Berrak Gumuskaya, Hameed Rahimi, Jessica Hicks, Tsuyoshi Iwata, Brian D Robinson, Jonathan I Epstein, Angelo M De MarzoAbstract:Cytoplasmic PTEN protein loss distinguishes Intraductal Carcinoma of the prostate from high-grade prostatic intraepithelial neoplasia
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cytoplasmic pten protein loss distinguishes Intraductal Carcinoma of the prostate from high grade prostatic intraepithelial neoplasia
Modern Pathology, 2013Co-Authors: Tamara L Lotan, Berrak Gumuskaya, Hameed Rahimi, Jessica Hicks, Tsuyoshi Iwata, Brian D Robinson, Jonathan I Epstein, Angelo M De MarzoAbstract:Intraductal Carcinoma of the prostate is a marker of aggressive disease. However, Intraductal Carcinoma exists on a morphologic continuum with high-grade prostatic intraepithelial neoplasia (PIN) and distinguishing Intraductal Carcinoma from PIN is a common diagnostic dilemma with significant clinical implications. We evaluated whether immunostains for PTEN and ERG can sensitively identify Intraductal Carcinoma and accurately distinguish it from high-grade PIN. A combined immunostain for PTEN, ERG, p63 and CK903 was developed and validated. Radical prostatectomy specimens with lesions meeting criteria for Intraductal Carcinoma (n=45), Intraductal cribriform proliferations falling short of Intraductal Carcinoma (n=15), and PIN lesions (n=39) were retrospectively identified and assessed for PTEN and ERG. Cytoplasmic PTEN loss was identified in 84% (38/45) of the Intraductal Carcinoma and 100% (15/15) of Intraductal cribriform proliferation cases. In contrast, cytoplasmic PTEN loss was never observed in PIN (0/39; P 95% and P<0.0001 for each), and substantially less for PIN and the concurrent invasive tumor (83% for PTEN and 67% for ERG; P=NS for each). Cytoplasmic PTEN loss occurs in the majority of Intraductal Carcinoma and Intraductal cribriform proliferation cases. Cytoplasmic PTEN loss was never observed in PIN (100% specificity). Our study identifies PTEN loss as a potentially useful marker to distinguish Intraductal Carcinoma from PIN and provides a plausible molecular explanation for why Intraductal Carcinoma is associated with poor prognosis.
Ming Zhou - One of the best experts on this subject based on the ideXlab platform.
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high grade prostatic intraepithelial neoplasia pin like Carcinoma ductal Carcinoma and Intraductal Carcinoma of the prostate
Modern Pathology, 2018Co-Authors: Ming ZhouAbstract:High-grade prostatic intraepithelial neoplasia, PIN-like Carcinoma, ductal Carcinoma, and Intraductal Carcinoma of the prostate
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utility of pten and erg immunostaining for distinguishing high grade pin from Intraductal Carcinoma of the prostate on needle biopsy
The American Journal of Surgical Pathology, 2015Co-Authors: Carlos L Morais, Cristina Magigalluzzi, Ming Zhou, Jessica Hicks, Jeong S Han, Jennifer Gordetsky, Michael S Nagar, Ann E Anderson, Stephen Lee, Rajal B ShahAbstract:Intraductal Carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to resolve this differential diagnosis. Here, we tested whether these markers are diagnostically useful in the needle biopsy setting. Separate or combined immunostains were applied to biopsies containing morphologically identified Intraductal Carcinoma, PIN, or borderline Intraductal proliferations more concerning than PIN but falling short of morphologic criteria for Intraductal Carcinoma. Intraductal Carcinoma occurring with concurrent invasive tumor showed the highest rate of PTEN loss, with 76% (38/50) lacking PTEN and 58% (29/50) expressing ERG. Of biopsies containing isolated Intraductal Carcinoma, 61% (20/33) showed PTEN loss and 30% (10/33) expressed ERG. Of the borderline Intraductal proliferations, 52% (11/21) showed PTEN loss and 27% (4/15) expressed ERG. Of the borderline cases with PTEN loss, 64% (7/11) had Carcinoma in a subsequent needle biopsy specimen, compared with 50% (5/10) of PTEN-intact cases. In contrast, none of the PIN cases showed PTEN loss or ERG expression (0/19). On needle biopsy, PTEN loss is common in morphologically identified Intraductal Carcinoma yet is very rare in high-grade PIN. Borderline Intraductal proliferations, especially those with PTEN loss, have a high rate of Carcinoma on resampling. If confirmed in larger prospective studies, these results suggest that PTEN and ERG immunostaining may provide a useful ancillary assay to distinguish Intraductal Carcinoma from high-grade PIN in this setting.
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utility of pten and erg immunostaining for distinguishing high grade pin from Intraductal Carcinoma of the prostate on needle biopsy
The American Journal of Surgical Pathology, 2015Co-Authors: Carlos L Morais, Rajal B Shah, Cristina Magigalluzzi, Ming Zhou, Jessica Hicks, Jennifer Gordetsky, Ann E Anderson, Jonathan I Epstein, Michael Nagar, Angelo M De MarzoAbstract:Intraductal Carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to
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incidence and clinicopathological characteristics of Intraductal Carcinoma detected in prostate biopsies a prospective cohort study
Histopathology, 2013Co-Authors: Katherine E Watts, Cristina Magigalluzzi, Jianbo Li, Ming ZhouAbstract:Aims Intraductal Carcinoma of the prostate (IDC-P) is a distinct clinicopathological entity and is associated with aggressive, high-grade and high-volume prostate Carcinoma (PCa). The incidence, clinicopathological characteristics and prognostic significance of IDC-P have not been reported in prostate biopsies (PBx) that surgical pathologists encounter in their daily practice. Methods and results In 1176 prospectively collected PBx, 33 IDC-P cases were identified (2.8%). The mean age of patients with IDC-P was 65 (range 46–79) years and mean serum prostate-specific antigen was 16.2 (range 0.4–105.6) ng/ml. Three (0.26%) IDC-P cases did not have a concomitant invasive PCa. Of 30 cases with concomitant invasive PCa, Gleason score was 7 in 16 (53.3%), 8 in four (13.3%) and 9 in 10 (33.3%) cases. The mean number of biopsy cores involved by PCa was 7.2 (range 1–14). Nine patients were treated with radical prostatectomy. Seminal vesicle invasion was found in four of nine (44%) cases, significantly higher than the risk of 12% predicted by Partin Tables (P = 0.016). Conclusions This is the first prospective study that has investigated the incidence and prognostic significance of IDC-P diagnosed in PBx encountered in daily practice. It is critical for surgical pathologists to diagnose and report IDC-P in PBx.
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do not misinterpret Intraductal Carcinoma of the prostate as high grade prostatic intraepithelial neoplasia
European Urology, 2012Co-Authors: Rodolfo Montironi, Marina Scarpelli, Liang Cheng, Antonio Lopezbeltran, Ming Zhou, Francesco MontorsiAbstract:a Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Pathology, Reina Sofia University Hospital and Faculty of Medicine, Cordoba, Spain; Department of Pathology, New York University Langone Medical Center, New York, NY, USA; Department of Urology, University Vita-Salute, Scientific Institute H San Raffaele, Milan, Italy
Rajal B Shah - One of the best experts on this subject based on the ideXlab platform.
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utility of pten and erg immunostaining for distinguishing high grade pin from Intraductal Carcinoma of the prostate on needle biopsy
The American Journal of Surgical Pathology, 2015Co-Authors: Carlos L Morais, Cristina Magigalluzzi, Ming Zhou, Jessica Hicks, Jeong S Han, Jennifer Gordetsky, Michael S Nagar, Ann E Anderson, Stephen Lee, Rajal B ShahAbstract:Intraductal Carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to resolve this differential diagnosis. Here, we tested whether these markers are diagnostically useful in the needle biopsy setting. Separate or combined immunostains were applied to biopsies containing morphologically identified Intraductal Carcinoma, PIN, or borderline Intraductal proliferations more concerning than PIN but falling short of morphologic criteria for Intraductal Carcinoma. Intraductal Carcinoma occurring with concurrent invasive tumor showed the highest rate of PTEN loss, with 76% (38/50) lacking PTEN and 58% (29/50) expressing ERG. Of biopsies containing isolated Intraductal Carcinoma, 61% (20/33) showed PTEN loss and 30% (10/33) expressed ERG. Of the borderline Intraductal proliferations, 52% (11/21) showed PTEN loss and 27% (4/15) expressed ERG. Of the borderline cases with PTEN loss, 64% (7/11) had Carcinoma in a subsequent needle biopsy specimen, compared with 50% (5/10) of PTEN-intact cases. In contrast, none of the PIN cases showed PTEN loss or ERG expression (0/19). On needle biopsy, PTEN loss is common in morphologically identified Intraductal Carcinoma yet is very rare in high-grade PIN. Borderline Intraductal proliferations, especially those with PTEN loss, have a high rate of Carcinoma on resampling. If confirmed in larger prospective studies, these results suggest that PTEN and ERG immunostaining may provide a useful ancillary assay to distinguish Intraductal Carcinoma from high-grade PIN in this setting.
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utility of pten and erg immunostaining for distinguishing high grade pin from Intraductal Carcinoma of the prostate on needle biopsy
The American Journal of Surgical Pathology, 2015Co-Authors: Carlos L Morais, Rajal B Shah, Cristina Magigalluzzi, Ming Zhou, Jessica Hicks, Jennifer Gordetsky, Ann E Anderson, Jonathan I Epstein, Michael Nagar, Angelo M De MarzoAbstract:Intraductal Carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to
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ets gene aberrations in atypical cribriform lesions of the prostate implications for the distinction between Intraductal Carcinoma of the prostate and cribriform high grade prostatic intraepithelial neoplasia
The American Journal of Surgical Pathology, 2010Co-Authors: Khalid Suleman, Linda Sercia, Javed Siddiqui, Arul M Chinnaiyan, Nallasivam Palanisamy, Rajal B Shah, Cristina Magigalluzzi, Ming ZhouAbstract:Background: Atypical cribriform lesions (ACLs) of the prostate consist of cribriform glands lined with cytologically malignant cells with partial or complete basal cell lining. It may represent cribriform ‘‘high-grade prostatic intraepithelial neoplasia’’ (HGPIN) or ‘‘Intraductal Carcinoma of the prostate’’ (IDC-P), which is almost always associated with clinically aggressive prostate Carcinoma (PCa). Distinction between these 2 lesions has profound clinical significance, especially on needle biopsies. However, there are lesions that do not fully satisfy the criteria for IDC-P yet are worse than typical HGPIN and are difficult to distinguish based on morphologic criteria alone. Methods: To better understand the biologic and molecular basis of distinction between cribriform HGPIN and IDC, we used break-apart fluorescence in-situ hybridization assay to assess ETS gene aberrations, a specific and commonest molecular alteration involving PCa, in a cohort of 16 isolated ACL, presumed to be an isolated cribriform HGPIN, and 45 Carcinoma-associated ACL (ACL-PCa) on radical prostatectomy specimens, presumed to be spectrum of IDC-P. The latter was further divided into 2 groups: group A with marked nuclear atypia (nuclear size 6 � normal or larger) and/or comedonecrosis (n = 21) and group B that did not fulfill these criteria (n = 24). Results: Overall, ERG rearrangement was absent (0 of 16) in isolated cribriform HGPIN, whereas present in 75% (36 of 48) of IDC-P, of which 65% (23 of 36) were through deletion and 35% (13 of 36) through insertion. Notably, 17% (6 of 36) of the IDC-P showed duplication of ERG rearrangement in combination with deletion of 5 0 -ERG. Hundred percent (34 of 34) of the IDC-P showed concordance of ERG rearrangement status with adjacent invasive Carcinoma. There was no difference between the 2 groups of IDC-P lesions regarding prevalence of ERG rearrangement (group A 79% vs. group B 74%) and EDel2+ (20% vs. 15%). No case with ETV1, ETV4, or ETV5 rearrangement was identified. Conclusions: Our molecular data suggest that isolated cribriform HGPIN and IDC-P are biologically distinct lesions. Majority of ACL-PCa most likely represent Intraductal spread of PCa. There is a significant overlap between IDC-P and HGPIN at the lower grade morphologic spectrum. ERG break-apart fluorescence in-situ hybridization assay provides insight into understanding the molecular basis of cribriform HGPIN and IDC-P and has potential clinical implications in their distinction on needle biopsies.
Jessica Hicks - One of the best experts on this subject based on the ideXlab platform.
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molecular evidence that invasive adenoCarcinoma can mimic prostatic intraepithelial neoplasia pin and Intraductal Carcinoma through retrograde glandular colonization
The Journal of Pathology, 2016Co-Authors: Michael C Haffner, Berrak Gumuskaya, Christopher Weier, Meng Meng Xu, Ajay Vaghasia, Bora Gurel, David M Esopi, Helen Fedor, Ibrahim Kulac, Jessica HicksAbstract:Prostate cancer often manifests as morphologically distinct tumour foci and is frequently found adjacent to presumed precursor lesions such as high-grade prostatic intraepithelial neoplasia (HGPIN). While there is some evidence to suggest that these lesions can be related and exist on a pathological and morphological continuum, the precise clonal and temporal relationships between precursor lesions and invasive cancers within individual tumours remain undefined. Here, we used molecular genetic, cytogenetic, and histological analyses to delineate clonal, temporal, and spatial relationships between HGPIN and cancer lesions with distinct morphological and molecular features. First, while confirming the previous finding that a substantial fraction of HGPIN lesions associated with ERG-positive cancers share rearrangements and overexpression of ERG, we found that a significant subset of such HGPIN glands exhibit only partial positivity for ERG. This suggests that such ERG-positive HGPIN cells either rapidly invade to form adenoCarcinoma or represent cancer cells that have partially invaded the ductal and acinar space in a retrograde manner. To clarify these possibilities, we used ERG expression status and TMPRSS2–ERG genomic breakpoints as markers of clonality, and PTEN deletion status to track temporal evolution of clonally related lesions. We confirmed that morphologically distinct HGPIN and nearby invasive cancer lesions are clonally related. Further, we found that a significant fraction of ERG-positive, PTEN-negative HGPIN and Intraductal Carcinoma (IDC-P) lesions are most likely clonally derived from adjacent PTEN-negative adenoCarcinomas, indicating that such PTEN-negative HGPIN and IDC-P lesions arise from, rather than give rise to, the nearby invasive adenoCarcinoma. These data suggest that invasive adenoCarcinoma can morphologically mimic HGPIN through retrograde colonization of benign glands with cancer cells. Similar clonal relationships were also seen for Intraductal Carcinoma adjacent to invasive adenoCarcinoma. These findings represent a potentially undervalued indicator of pre-existing invasive prostate cancer and have significant implications for prostate cancer diagnosis and risk stratification.
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utility of pten and erg immunostaining for distinguishing high grade pin from Intraductal Carcinoma of the prostate on needle biopsy
The American Journal of Surgical Pathology, 2015Co-Authors: Carlos L Morais, Cristina Magigalluzzi, Ming Zhou, Jessica Hicks, Jeong S Han, Jennifer Gordetsky, Michael S Nagar, Ann E Anderson, Stephen Lee, Rajal B ShahAbstract:Intraductal Carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to resolve this differential diagnosis. Here, we tested whether these markers are diagnostically useful in the needle biopsy setting. Separate or combined immunostains were applied to biopsies containing morphologically identified Intraductal Carcinoma, PIN, or borderline Intraductal proliferations more concerning than PIN but falling short of morphologic criteria for Intraductal Carcinoma. Intraductal Carcinoma occurring with concurrent invasive tumor showed the highest rate of PTEN loss, with 76% (38/50) lacking PTEN and 58% (29/50) expressing ERG. Of biopsies containing isolated Intraductal Carcinoma, 61% (20/33) showed PTEN loss and 30% (10/33) expressed ERG. Of the borderline Intraductal proliferations, 52% (11/21) showed PTEN loss and 27% (4/15) expressed ERG. Of the borderline cases with PTEN loss, 64% (7/11) had Carcinoma in a subsequent needle biopsy specimen, compared with 50% (5/10) of PTEN-intact cases. In contrast, none of the PIN cases showed PTEN loss or ERG expression (0/19). On needle biopsy, PTEN loss is common in morphologically identified Intraductal Carcinoma yet is very rare in high-grade PIN. Borderline Intraductal proliferations, especially those with PTEN loss, have a high rate of Carcinoma on resampling. If confirmed in larger prospective studies, these results suggest that PTEN and ERG immunostaining may provide a useful ancillary assay to distinguish Intraductal Carcinoma from high-grade PIN in this setting.
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utility of pten and erg immunostaining for distinguishing high grade pin from Intraductal Carcinoma of the prostate on needle biopsy
The American Journal of Surgical Pathology, 2015Co-Authors: Carlos L Morais, Rajal B Shah, Cristina Magigalluzzi, Ming Zhou, Jessica Hicks, Jennifer Gordetsky, Ann E Anderson, Jonathan I Epstein, Michael Nagar, Angelo M De MarzoAbstract:Intraductal Carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to
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cytoplasmic pten protein loss distinguishes Intraductal Carcinoma of the prostate from high grade prostatic intraepithelial neoplasia
Modern Pathology, 2013Co-Authors: Tamara L Lotan, Berrak Gumuskaya, Hameed Rahimi, Jessica Hicks, Tsuyoshi Iwata, Brian D Robinson, Jonathan I Epstein, Angelo M De MarzoAbstract:Cytoplasmic PTEN protein loss distinguishes Intraductal Carcinoma of the prostate from high-grade prostatic intraepithelial neoplasia
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cytoplasmic pten protein loss distinguishes Intraductal Carcinoma of the prostate from high grade prostatic intraepithelial neoplasia
Modern Pathology, 2013Co-Authors: Tamara L Lotan, Berrak Gumuskaya, Hameed Rahimi, Jessica Hicks, Tsuyoshi Iwata, Brian D Robinson, Jonathan I Epstein, Angelo M De MarzoAbstract:Intraductal Carcinoma of the prostate is a marker of aggressive disease. However, Intraductal Carcinoma exists on a morphologic continuum with high-grade prostatic intraepithelial neoplasia (PIN) and distinguishing Intraductal Carcinoma from PIN is a common diagnostic dilemma with significant clinical implications. We evaluated whether immunostains for PTEN and ERG can sensitively identify Intraductal Carcinoma and accurately distinguish it from high-grade PIN. A combined immunostain for PTEN, ERG, p63 and CK903 was developed and validated. Radical prostatectomy specimens with lesions meeting criteria for Intraductal Carcinoma (n=45), Intraductal cribriform proliferations falling short of Intraductal Carcinoma (n=15), and PIN lesions (n=39) were retrospectively identified and assessed for PTEN and ERG. Cytoplasmic PTEN loss was identified in 84% (38/45) of the Intraductal Carcinoma and 100% (15/15) of Intraductal cribriform proliferation cases. In contrast, cytoplasmic PTEN loss was never observed in PIN (0/39; P 95% and P<0.0001 for each), and substantially less for PIN and the concurrent invasive tumor (83% for PTEN and 67% for ERG; P=NS for each). Cytoplasmic PTEN loss occurs in the majority of Intraductal Carcinoma and Intraductal cribriform proliferation cases. Cytoplasmic PTEN loss was never observed in PIN (100% specificity). Our study identifies PTEN loss as a potentially useful marker to distinguish Intraductal Carcinoma from PIN and provides a plausible molecular explanation for why Intraductal Carcinoma is associated with poor prognosis.