The Experts below are selected from a list of 51951 Experts worldwide ranked by ideXlab platform
Liang Cheng - One of the best experts on this subject based on the ideXlab platform.
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erg tmprss2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder evidence supporting monoclonal origin
Modern Pathology, 2011Co-Authors: Sean R Williamson, Gregory T Maclennan, Antonio Lopezbeltran, Shaobo Zhang, Jiaoti Huang, Rodolfo Montironi, Steven S Shen, Adeboye O Osunkoya, Liang ChengAbstract:ERG–TMPRSS2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder: evidence supporting monoclonal origin
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erg tmprss2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder evidence supporting monoclonal origin
Modern Pathology, 2011Co-Authors: Sean R Williamson, Gregory T Maclennan, Antonio Lopezbeltran, Shaobo Zhang, Jorge L Yao, Jiaoti Huang, Rodolfo Montironi, Steven S Shen, Adeboye O Osunkoya, Liang ChengAbstract:Prostatic Carcinoma is a heterogeneous disease with frequent multifocality and variability in morphology. Particularly, prostatic Small Cell Carcinoma is a rare variant with aggressive behavior. Distinction between Small Cell Carcinoma of the prostate and urinary bladder may be challenging, especially in Small biopsy specimens without associated prostatic adenoCarcinoma or urothelial Carcinoma. Recently, gene fusions between ETS genes, particularly ETS-related gene (ERG), and transmembrane protease, serine 2 (TMPRSS2) have been identified as a frequent event in prostate cancer. Thus, molecular methods may be helpful in determining the primary site of Small Cell Carcinoma. Thirty cases of prostatic Small Cell Carcinoma from the authors' archives were studied, among which 13 had concurrent prostatic adenoCarcinoma. Tricolor fluorescence in situ hybridization (FISH) was performed on formalin-fixed paraffin-embedded tissue sections with a probe cocktail for 3'/5' ERG and TMPRSS2. Cases of Small Cell Carcinoma of the bladder and conventional prostatic adenoCarcinoma (25 each) were also tested as controls. ERG gene alterations were found only in prostate malignancies and not in benign prostatic tissue or bladder Small Cell Carcinoma. TMPRSS2-ERG gene fusion was found in 47% (14/30) of prostatic Small Cell Carcinoma. Of cases with concurrent prostatic adenoCarcinoma, 85% (11/13) had identical findings in both components. In 20% of rearranged cases, the ERG abnormality was associated with 5' ERG deletion. In 17% (5/30) of cases, gain of the 21q22 locus was present. Two cases showed discordant aberrations in the Small Cell Carcinoma and adenoCarcinoma, one with deletion of 5' ERG and one with gain of chromosome 21q, both in only the adenoCarcinoma component. Small Cell Carcinoma of the prostate demonstrates TMPRSS2-ERG rearrangement with comparable frequency to prostatic adenoCarcinoma. In cases with concurrent adenoCarcinoma and Small Cell Carcinoma, the majority showed identical abnormalities in both components, indicating a likely common clonal origin. Discordant alterations were present in rare cases, suggesting that acquisition of additional genetic changes in multifocal tumors may be responsible for disease progression to a more aggressive phenotype. TMPRSS2-ERG fusion is absent in bladder Small Cell Carcinoma, supporting the utility of FISH in distinguishing prostate from bladder primary tumors and identifying metastatic Small Cell Carcinoma of unknown origin.
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Small Cell Carcinoma of the urinary bladder histogenesis genetics diagnosis biomarkers treatment and prognosis
Applied Immunohistochemistry & Molecular Morphology, 2007Co-Authors: Xiaoyan Wang, Antonio Lopezbeltran, Gregory T Maclennan, Liang ChengAbstract:Small Cell Carcinoma of the urinary bladder is a rare but highly aggressive malignancy with a dismal prognosis. Most patients present with advanced disease at the time of diagnosis. Hematuria is the most frequent presenting symptom. Histologically, Small Cell Carcinoma of the urinary bladder is indistinguishable from its pulmonary counterpart. Coexistence with other types of Carcinoma is common. Histogenesis is uncertain; there are several competing theories, including origin from stem Cells, from urothelial Cells, and from neuroendocrine Cells in normal or metaplastic urothelium. The molecular pathogenesis remains unclear. Immunohistochemical staining can be extremely helpful in establishing the diagnosis, and in investigating the use of potential therapeutic strategies. Currently, combinations of surgical resection, chemotherapy, and radiation therapy represent the main treatment options. The recent observation of c-kit and epidermal growth factor receptor expression in more than 25% of patients with urinary bladder Small Cell Carcinoma opens new avenues for further investigation. Improvement in survival may depend upon the identification of new molecular markers to facilitate earlier diagnosis and the development of novel targeted therapies. In this paper, we review general aspects of Small Cell Carcinoma of the urinary bladder, focusing on the ways in which our understanding of this entity has been positively influenced by studies of the histopathologic and immunohistochemical findings, and by investigations of genetic alterations in this disease.
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Small Cell Carcinoma of the prostate an immunohistochemical study
The American Journal of Surgical Pathology, 2006Co-Authors: Ralph Madeb, Ximing J Yang, Liang Cheng, Jiaoti Huang, Patricia A Bourne, Satish K Tickoo, Fadi Hatem, Anthony P Di SantagneseAbstract:Small Cell Carcinoma of the prostate (SCPC) is morphologically similar to Small Cell Carcinoma of the lung (SCLC) and maybe misinterpreted as Gleason pattern 5b prostate adenoCarcinoma (HGPC). Recognition of SCPC is important because of its different clinical behavior. This study aims to characterize the immunophenotype of histologically classic SCPC using a comprehensive panel of markers, to better understand its histogenesis, aid in its classification, and evaluate potential therapeutic targets. Using the World Health Organization morphologic criteria for SCLC, 18 SCPC cases were identified; and studied for the following tumor marker groups: prostate specific/related, neuroendocrine, sex steroid hormone receptors, and prognostic/treatment target-related. Ten cases of UPC were used as controls. PSA was positive in 17% of SCPC and neuroendocrine markers were expressed in HGPC. PSA, TTF-1 and CD56 were the most helpful markers in differentiating between SCPC and HGPC (P<0.01), whereas bombesin/GRP, c-kit, bcl-2, and EGFR expression was more frequent in SCPC. SCPC is best diagnosed by following the World Health Organization diagnostic criteria for SCLC. Immunohistochemical markers can help separate SCPC from HGPC and may be useful in histologically borderline cases. Potential therapeutic targets are identified immunohistochemically in SCPC (Bombesin/GRP, c-kit, bcl-2, and EGFR).
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thyroid transcription factor 1 expression in Small Cell Carcinoma of the urinary bladder an immunohistochemical profile of 44 cases
Human Pathology, 2005Co-Authors: Timothy D Jones, Kevin M Kernek, Lee Ann Baldridge, Ximing J Yang, Maria Tretiakova, John N Eble, Gregory T Maclennan, Antonio Lopezbeltran, Liang ChengAbstract:Summary Small Cell Carcinoma of the urinary bladder is a rare and aggressive tumor resembling Small Cell Carcinoma of the lung. Thyroid transcription factor 1 (TTF-1) expression is common in Small Cell Carcinomas arising in the lung. However, studies of its expression in extrapulmonary Small Cell Carcinomas have yielded varying results. Because information concerning the immunohistochemical profile of Small Cell Carcinoma of the urinary bladder is limited, we investigated the immunoreactivity of this tumor to a battery of antibodies in a series of 44 cases. Using 5- μ m sections cut from paraffin-embedded tissue blocks, immunohistochemistry was performed to detect TTF-1, cytokeratin (CK) 7, CK20, and uroplakin antigenicity in 44 cases of Small Cell Carcinoma of the urinary bladder. None of the patients had primary lung tumors. The TTF-1 immunohistochemical stain showed nuclear positivity in 17 cases (39%). Positive immunostaining for CK7 was observed in 26 cases (59%). There was no positive staining with either CK20 or uroplakin. There was no correlation between TTF-1 expression and survival ( P = .27). In addition, TTF-1 expression did not correlate with clinicopathological characteristics, including age ( P = .74), sex ( P = .53), smoking history ( P = .96), clinical stage ( P = .10), pathological T stage ( P = .50), lymph node metastasis ( P = .40), and distant metastasis ( P = .58). In summary, TTF-1 expression in Small Cell Carcinoma of the urinary bladder was found in 39% of the tumors, demonstrating that this marker is expressed in Small Cell Carcinomas other than those of pulmonary origin. Small Cell Carcinoma of the urinary bladder is positive for CK7 immunostaining in 59% of cases consistent with its origin from urothelium. Unlike urothelial Carcinoma, expression of CK20 and uroplakin in Small Cell Carcinoma of the urinary bladder is consistently negative, and thus, these stains do not appear to be useful in the diagnosis of this neoplasm. TTF-1 positivity is not a significant prognostic factor in Small Cell Carcinoma of the urinary bladder.
Antonio Lopezbeltran - One of the best experts on this subject based on the ideXlab platform.
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frequent tmprss2 erg rearrangement in prostatic Small Cell Carcinoma detected by fluorescence in situ hybridization the superiority of fluorescence in situ hybridization over erg immunohistochemistry
Human Pathology, 2013Co-Authors: Lindsay A Schelling, Antonio Lopezbeltran, Sean R Williamson, Shaobo Zhang, Jorge L Yao, Mingsheng Wang, Jiaoti Huang, Rodolfo Montironi, Robert E Emerson, Muhammad T IdreesAbstract:Small Cell Carcinoma of the prostate is both morphologically and immunohistochemically similar to Small Cell Carcinoma of other organs such as the urinary bladder or lung. TMPRSS2-ERG gene fusion appears to be a highly specific alteration in prostatic Carcinoma that is frequently shared by Small Cell Carcinoma. In adenoCarcinoma, immunohistochemistry for the ERG protein product has been reported to correlate well with the presence of the gene fusion, although in prostatic Small Cell Carcinoma, this relationship is not completely understood. We evaluated 54 cases of Small Cell Carcinoma of the prostate and compared TMPRSS2-ERG gene fusion status by fluorescence in situ hybridization (FISH) to immunohistochemical staining with antibody to ERG. Of 54 cases of prostatic Small Cell Carcinoma, 26 (48%) were positive for TMPRSS2-ERG gene fusion by FISH and 12 (22%) showed overexpression of ERG protein by immunohistochemistry. Of the 26 cases positive by FISH, 11 were also positive for ERG protein by immunohistochemistry. One tumor was positive by immunohistochemistry but negative by FISH. Urinary bladder Small Cell Carcinoma (n = 25) showed negative results by both methods; however, 2 of 14 Small Cell Carcinomas of other organs (lung, head, and neck) showed positive immunohistochemistry but negative FISH. Positive staining for ERG by immunohistochemistry is present in a subset of prostatic Small Cell Carcinomas and correlates with the presence of TMPRSS2-ERG gene fusion. Therefore, it may be useful in confirming prostatic origin when molecular testing is not accessible. However, sensitivity and specificity of ERG immunohistochemistry in Small Cell Carcinoma are decreased compared to FISH.
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erg tmprss2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder evidence supporting monoclonal origin
Modern Pathology, 2011Co-Authors: Sean R Williamson, Gregory T Maclennan, Antonio Lopezbeltran, Shaobo Zhang, Jorge L Yao, Jiaoti Huang, Rodolfo Montironi, Steven S Shen, Adeboye O Osunkoya, Liang ChengAbstract:Prostatic Carcinoma is a heterogeneous disease with frequent multifocality and variability in morphology. Particularly, prostatic Small Cell Carcinoma is a rare variant with aggressive behavior. Distinction between Small Cell Carcinoma of the prostate and urinary bladder may be challenging, especially in Small biopsy specimens without associated prostatic adenoCarcinoma or urothelial Carcinoma. Recently, gene fusions between ETS genes, particularly ETS-related gene (ERG), and transmembrane protease, serine 2 (TMPRSS2) have been identified as a frequent event in prostate cancer. Thus, molecular methods may be helpful in determining the primary site of Small Cell Carcinoma. Thirty cases of prostatic Small Cell Carcinoma from the authors' archives were studied, among which 13 had concurrent prostatic adenoCarcinoma. Tricolor fluorescence in situ hybridization (FISH) was performed on formalin-fixed paraffin-embedded tissue sections with a probe cocktail for 3'/5' ERG and TMPRSS2. Cases of Small Cell Carcinoma of the bladder and conventional prostatic adenoCarcinoma (25 each) were also tested as controls. ERG gene alterations were found only in prostate malignancies and not in benign prostatic tissue or bladder Small Cell Carcinoma. TMPRSS2-ERG gene fusion was found in 47% (14/30) of prostatic Small Cell Carcinoma. Of cases with concurrent prostatic adenoCarcinoma, 85% (11/13) had identical findings in both components. In 20% of rearranged cases, the ERG abnormality was associated with 5' ERG deletion. In 17% (5/30) of cases, gain of the 21q22 locus was present. Two cases showed discordant aberrations in the Small Cell Carcinoma and adenoCarcinoma, one with deletion of 5' ERG and one with gain of chromosome 21q, both in only the adenoCarcinoma component. Small Cell Carcinoma of the prostate demonstrates TMPRSS2-ERG rearrangement with comparable frequency to prostatic adenoCarcinoma. In cases with concurrent adenoCarcinoma and Small Cell Carcinoma, the majority showed identical abnormalities in both components, indicating a likely common clonal origin. Discordant alterations were present in rare cases, suggesting that acquisition of additional genetic changes in multifocal tumors may be responsible for disease progression to a more aggressive phenotype. TMPRSS2-ERG fusion is absent in bladder Small Cell Carcinoma, supporting the utility of FISH in distinguishing prostate from bladder primary tumors and identifying metastatic Small Cell Carcinoma of unknown origin.
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erg tmprss2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder evidence supporting monoclonal origin
Modern Pathology, 2011Co-Authors: Sean R Williamson, Gregory T Maclennan, Antonio Lopezbeltran, Shaobo Zhang, Jiaoti Huang, Rodolfo Montironi, Steven S Shen, Adeboye O Osunkoya, Liang ChengAbstract:ERG–TMPRSS2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder: evidence supporting monoclonal origin
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Small Cell Carcinoma of the urinary bladder histogenesis genetics diagnosis biomarkers treatment and prognosis
Applied Immunohistochemistry & Molecular Morphology, 2007Co-Authors: Xiaoyan Wang, Antonio Lopezbeltran, Gregory T Maclennan, Liang ChengAbstract:Small Cell Carcinoma of the urinary bladder is a rare but highly aggressive malignancy with a dismal prognosis. Most patients present with advanced disease at the time of diagnosis. Hematuria is the most frequent presenting symptom. Histologically, Small Cell Carcinoma of the urinary bladder is indistinguishable from its pulmonary counterpart. Coexistence with other types of Carcinoma is common. Histogenesis is uncertain; there are several competing theories, including origin from stem Cells, from urothelial Cells, and from neuroendocrine Cells in normal or metaplastic urothelium. The molecular pathogenesis remains unclear. Immunohistochemical staining can be extremely helpful in establishing the diagnosis, and in investigating the use of potential therapeutic strategies. Currently, combinations of surgical resection, chemotherapy, and radiation therapy represent the main treatment options. The recent observation of c-kit and epidermal growth factor receptor expression in more than 25% of patients with urinary bladder Small Cell Carcinoma opens new avenues for further investigation. Improvement in survival may depend upon the identification of new molecular markers to facilitate earlier diagnosis and the development of novel targeted therapies. In this paper, we review general aspects of Small Cell Carcinoma of the urinary bladder, focusing on the ways in which our understanding of this entity has been positively influenced by studies of the histopathologic and immunohistochemical findings, and by investigations of genetic alterations in this disease.
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thyroid transcription factor 1 expression in Small Cell Carcinoma of the urinary bladder an immunohistochemical profile of 44 cases
Human Pathology, 2005Co-Authors: Timothy D Jones, Kevin M Kernek, Lee Ann Baldridge, Ximing J Yang, Maria Tretiakova, John N Eble, Gregory T Maclennan, Antonio Lopezbeltran, Liang ChengAbstract:Summary Small Cell Carcinoma of the urinary bladder is a rare and aggressive tumor resembling Small Cell Carcinoma of the lung. Thyroid transcription factor 1 (TTF-1) expression is common in Small Cell Carcinomas arising in the lung. However, studies of its expression in extrapulmonary Small Cell Carcinomas have yielded varying results. Because information concerning the immunohistochemical profile of Small Cell Carcinoma of the urinary bladder is limited, we investigated the immunoreactivity of this tumor to a battery of antibodies in a series of 44 cases. Using 5- μ m sections cut from paraffin-embedded tissue blocks, immunohistochemistry was performed to detect TTF-1, cytokeratin (CK) 7, CK20, and uroplakin antigenicity in 44 cases of Small Cell Carcinoma of the urinary bladder. None of the patients had primary lung tumors. The TTF-1 immunohistochemical stain showed nuclear positivity in 17 cases (39%). Positive immunostaining for CK7 was observed in 26 cases (59%). There was no positive staining with either CK20 or uroplakin. There was no correlation between TTF-1 expression and survival ( P = .27). In addition, TTF-1 expression did not correlate with clinicopathological characteristics, including age ( P = .74), sex ( P = .53), smoking history ( P = .96), clinical stage ( P = .10), pathological T stage ( P = .50), lymph node metastasis ( P = .40), and distant metastasis ( P = .58). In summary, TTF-1 expression in Small Cell Carcinoma of the urinary bladder was found in 39% of the tumors, demonstrating that this marker is expressed in Small Cell Carcinomas other than those of pulmonary origin. Small Cell Carcinoma of the urinary bladder is positive for CK7 immunostaining in 59% of cases consistent with its origin from urothelium. Unlike urothelial Carcinoma, expression of CK20 and uroplakin in Small Cell Carcinoma of the urinary bladder is consistently negative, and thus, these stains do not appear to be useful in the diagnosis of this neoplasm. TTF-1 positivity is not a significant prognostic factor in Small Cell Carcinoma of the urinary bladder.
Gregory T Maclennan - One of the best experts on this subject based on the ideXlab platform.
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erg tmprss2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder evidence supporting monoclonal origin
Modern Pathology, 2011Co-Authors: Sean R Williamson, Gregory T Maclennan, Antonio Lopezbeltran, Shaobo Zhang, Jiaoti Huang, Rodolfo Montironi, Steven S Shen, Adeboye O Osunkoya, Liang ChengAbstract:ERG–TMPRSS2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder: evidence supporting monoclonal origin
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erg tmprss2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder evidence supporting monoclonal origin
Modern Pathology, 2011Co-Authors: Sean R Williamson, Gregory T Maclennan, Antonio Lopezbeltran, Shaobo Zhang, Jorge L Yao, Jiaoti Huang, Rodolfo Montironi, Steven S Shen, Adeboye O Osunkoya, Liang ChengAbstract:Prostatic Carcinoma is a heterogeneous disease with frequent multifocality and variability in morphology. Particularly, prostatic Small Cell Carcinoma is a rare variant with aggressive behavior. Distinction between Small Cell Carcinoma of the prostate and urinary bladder may be challenging, especially in Small biopsy specimens without associated prostatic adenoCarcinoma or urothelial Carcinoma. Recently, gene fusions between ETS genes, particularly ETS-related gene (ERG), and transmembrane protease, serine 2 (TMPRSS2) have been identified as a frequent event in prostate cancer. Thus, molecular methods may be helpful in determining the primary site of Small Cell Carcinoma. Thirty cases of prostatic Small Cell Carcinoma from the authors' archives were studied, among which 13 had concurrent prostatic adenoCarcinoma. Tricolor fluorescence in situ hybridization (FISH) was performed on formalin-fixed paraffin-embedded tissue sections with a probe cocktail for 3'/5' ERG and TMPRSS2. Cases of Small Cell Carcinoma of the bladder and conventional prostatic adenoCarcinoma (25 each) were also tested as controls. ERG gene alterations were found only in prostate malignancies and not in benign prostatic tissue or bladder Small Cell Carcinoma. TMPRSS2-ERG gene fusion was found in 47% (14/30) of prostatic Small Cell Carcinoma. Of cases with concurrent prostatic adenoCarcinoma, 85% (11/13) had identical findings in both components. In 20% of rearranged cases, the ERG abnormality was associated with 5' ERG deletion. In 17% (5/30) of cases, gain of the 21q22 locus was present. Two cases showed discordant aberrations in the Small Cell Carcinoma and adenoCarcinoma, one with deletion of 5' ERG and one with gain of chromosome 21q, both in only the adenoCarcinoma component. Small Cell Carcinoma of the prostate demonstrates TMPRSS2-ERG rearrangement with comparable frequency to prostatic adenoCarcinoma. In cases with concurrent adenoCarcinoma and Small Cell Carcinoma, the majority showed identical abnormalities in both components, indicating a likely common clonal origin. Discordant alterations were present in rare cases, suggesting that acquisition of additional genetic changes in multifocal tumors may be responsible for disease progression to a more aggressive phenotype. TMPRSS2-ERG fusion is absent in bladder Small Cell Carcinoma, supporting the utility of FISH in distinguishing prostate from bladder primary tumors and identifying metastatic Small Cell Carcinoma of unknown origin.
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Small Cell Carcinoma of the urinary bladder histogenesis genetics diagnosis biomarkers treatment and prognosis
Applied Immunohistochemistry & Molecular Morphology, 2007Co-Authors: Xiaoyan Wang, Antonio Lopezbeltran, Gregory T Maclennan, Liang ChengAbstract:Small Cell Carcinoma of the urinary bladder is a rare but highly aggressive malignancy with a dismal prognosis. Most patients present with advanced disease at the time of diagnosis. Hematuria is the most frequent presenting symptom. Histologically, Small Cell Carcinoma of the urinary bladder is indistinguishable from its pulmonary counterpart. Coexistence with other types of Carcinoma is common. Histogenesis is uncertain; there are several competing theories, including origin from stem Cells, from urothelial Cells, and from neuroendocrine Cells in normal or metaplastic urothelium. The molecular pathogenesis remains unclear. Immunohistochemical staining can be extremely helpful in establishing the diagnosis, and in investigating the use of potential therapeutic strategies. Currently, combinations of surgical resection, chemotherapy, and radiation therapy represent the main treatment options. The recent observation of c-kit and epidermal growth factor receptor expression in more than 25% of patients with urinary bladder Small Cell Carcinoma opens new avenues for further investigation. Improvement in survival may depend upon the identification of new molecular markers to facilitate earlier diagnosis and the development of novel targeted therapies. In this paper, we review general aspects of Small Cell Carcinoma of the urinary bladder, focusing on the ways in which our understanding of this entity has been positively influenced by studies of the histopathologic and immunohistochemical findings, and by investigations of genetic alterations in this disease.
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thyroid transcription factor 1 expression in Small Cell Carcinoma of the urinary bladder an immunohistochemical profile of 44 cases
Human Pathology, 2005Co-Authors: Timothy D Jones, Kevin M Kernek, Lee Ann Baldridge, Ximing J Yang, Maria Tretiakova, John N Eble, Gregory T Maclennan, Antonio Lopezbeltran, Liang ChengAbstract:Summary Small Cell Carcinoma of the urinary bladder is a rare and aggressive tumor resembling Small Cell Carcinoma of the lung. Thyroid transcription factor 1 (TTF-1) expression is common in Small Cell Carcinomas arising in the lung. However, studies of its expression in extrapulmonary Small Cell Carcinomas have yielded varying results. Because information concerning the immunohistochemical profile of Small Cell Carcinoma of the urinary bladder is limited, we investigated the immunoreactivity of this tumor to a battery of antibodies in a series of 44 cases. Using 5- μ m sections cut from paraffin-embedded tissue blocks, immunohistochemistry was performed to detect TTF-1, cytokeratin (CK) 7, CK20, and uroplakin antigenicity in 44 cases of Small Cell Carcinoma of the urinary bladder. None of the patients had primary lung tumors. The TTF-1 immunohistochemical stain showed nuclear positivity in 17 cases (39%). Positive immunostaining for CK7 was observed in 26 cases (59%). There was no positive staining with either CK20 or uroplakin. There was no correlation between TTF-1 expression and survival ( P = .27). In addition, TTF-1 expression did not correlate with clinicopathological characteristics, including age ( P = .74), sex ( P = .53), smoking history ( P = .96), clinical stage ( P = .10), pathological T stage ( P = .50), lymph node metastasis ( P = .40), and distant metastasis ( P = .58). In summary, TTF-1 expression in Small Cell Carcinoma of the urinary bladder was found in 39% of the tumors, demonstrating that this marker is expressed in Small Cell Carcinomas other than those of pulmonary origin. Small Cell Carcinoma of the urinary bladder is positive for CK7 immunostaining in 59% of cases consistent with its origin from urothelium. Unlike urothelial Carcinoma, expression of CK20 and uroplakin in Small Cell Carcinoma of the urinary bladder is consistently negative, and thus, these stains do not appear to be useful in the diagnosis of this neoplasm. TTF-1 positivity is not a significant prognostic factor in Small Cell Carcinoma of the urinary bladder.
Jiaoti Huang - One of the best experts on this subject based on the ideXlab platform.
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frequent tmprss2 erg rearrangement in prostatic Small Cell Carcinoma detected by fluorescence in situ hybridization the superiority of fluorescence in situ hybridization over erg immunohistochemistry
Human Pathology, 2013Co-Authors: Lindsay A Schelling, Antonio Lopezbeltran, Sean R Williamson, Shaobo Zhang, Jorge L Yao, Mingsheng Wang, Jiaoti Huang, Rodolfo Montironi, Robert E Emerson, Muhammad T IdreesAbstract:Small Cell Carcinoma of the prostate is both morphologically and immunohistochemically similar to Small Cell Carcinoma of other organs such as the urinary bladder or lung. TMPRSS2-ERG gene fusion appears to be a highly specific alteration in prostatic Carcinoma that is frequently shared by Small Cell Carcinoma. In adenoCarcinoma, immunohistochemistry for the ERG protein product has been reported to correlate well with the presence of the gene fusion, although in prostatic Small Cell Carcinoma, this relationship is not completely understood. We evaluated 54 cases of Small Cell Carcinoma of the prostate and compared TMPRSS2-ERG gene fusion status by fluorescence in situ hybridization (FISH) to immunohistochemical staining with antibody to ERG. Of 54 cases of prostatic Small Cell Carcinoma, 26 (48%) were positive for TMPRSS2-ERG gene fusion by FISH and 12 (22%) showed overexpression of ERG protein by immunohistochemistry. Of the 26 cases positive by FISH, 11 were also positive for ERG protein by immunohistochemistry. One tumor was positive by immunohistochemistry but negative by FISH. Urinary bladder Small Cell Carcinoma (n = 25) showed negative results by both methods; however, 2 of 14 Small Cell Carcinomas of other organs (lung, head, and neck) showed positive immunohistochemistry but negative FISH. Positive staining for ERG by immunohistochemistry is present in a subset of prostatic Small Cell Carcinomas and correlates with the presence of TMPRSS2-ERG gene fusion. Therefore, it may be useful in confirming prostatic origin when molecular testing is not accessible. However, sensitivity and specificity of ERG immunohistochemistry in Small Cell Carcinoma are decreased compared to FISH.
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erg tmprss2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder evidence supporting monoclonal origin
Modern Pathology, 2011Co-Authors: Sean R Williamson, Gregory T Maclennan, Antonio Lopezbeltran, Shaobo Zhang, Jorge L Yao, Jiaoti Huang, Rodolfo Montironi, Steven S Shen, Adeboye O Osunkoya, Liang ChengAbstract:Prostatic Carcinoma is a heterogeneous disease with frequent multifocality and variability in morphology. Particularly, prostatic Small Cell Carcinoma is a rare variant with aggressive behavior. Distinction between Small Cell Carcinoma of the prostate and urinary bladder may be challenging, especially in Small biopsy specimens without associated prostatic adenoCarcinoma or urothelial Carcinoma. Recently, gene fusions between ETS genes, particularly ETS-related gene (ERG), and transmembrane protease, serine 2 (TMPRSS2) have been identified as a frequent event in prostate cancer. Thus, molecular methods may be helpful in determining the primary site of Small Cell Carcinoma. Thirty cases of prostatic Small Cell Carcinoma from the authors' archives were studied, among which 13 had concurrent prostatic adenoCarcinoma. Tricolor fluorescence in situ hybridization (FISH) was performed on formalin-fixed paraffin-embedded tissue sections with a probe cocktail for 3'/5' ERG and TMPRSS2. Cases of Small Cell Carcinoma of the bladder and conventional prostatic adenoCarcinoma (25 each) were also tested as controls. ERG gene alterations were found only in prostate malignancies and not in benign prostatic tissue or bladder Small Cell Carcinoma. TMPRSS2-ERG gene fusion was found in 47% (14/30) of prostatic Small Cell Carcinoma. Of cases with concurrent prostatic adenoCarcinoma, 85% (11/13) had identical findings in both components. In 20% of rearranged cases, the ERG abnormality was associated with 5' ERG deletion. In 17% (5/30) of cases, gain of the 21q22 locus was present. Two cases showed discordant aberrations in the Small Cell Carcinoma and adenoCarcinoma, one with deletion of 5' ERG and one with gain of chromosome 21q, both in only the adenoCarcinoma component. Small Cell Carcinoma of the prostate demonstrates TMPRSS2-ERG rearrangement with comparable frequency to prostatic adenoCarcinoma. In cases with concurrent adenoCarcinoma and Small Cell Carcinoma, the majority showed identical abnormalities in both components, indicating a likely common clonal origin. Discordant alterations were present in rare cases, suggesting that acquisition of additional genetic changes in multifocal tumors may be responsible for disease progression to a more aggressive phenotype. TMPRSS2-ERG fusion is absent in bladder Small Cell Carcinoma, supporting the utility of FISH in distinguishing prostate from bladder primary tumors and identifying metastatic Small Cell Carcinoma of unknown origin.
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erg tmprss2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder evidence supporting monoclonal origin
Modern Pathology, 2011Co-Authors: Sean R Williamson, Gregory T Maclennan, Antonio Lopezbeltran, Shaobo Zhang, Jiaoti Huang, Rodolfo Montironi, Steven S Shen, Adeboye O Osunkoya, Liang ChengAbstract:ERG–TMPRSS2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder: evidence supporting monoclonal origin
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Small Cell Carcinoma of the prostate an immunohistochemical study
The American Journal of Surgical Pathology, 2006Co-Authors: Ralph Madeb, Ximing J Yang, Liang Cheng, Jiaoti Huang, Patricia A Bourne, Satish K Tickoo, Fadi Hatem, Anthony P Di SantagneseAbstract:Small Cell Carcinoma of the prostate (SCPC) is morphologically similar to Small Cell Carcinoma of the lung (SCLC) and maybe misinterpreted as Gleason pattern 5b prostate adenoCarcinoma (HGPC). Recognition of SCPC is important because of its different clinical behavior. This study aims to characterize the immunophenotype of histologically classic SCPC using a comprehensive panel of markers, to better understand its histogenesis, aid in its classification, and evaluate potential therapeutic targets. Using the World Health Organization morphologic criteria for SCLC, 18 SCPC cases were identified; and studied for the following tumor marker groups: prostate specific/related, neuroendocrine, sex steroid hormone receptors, and prognostic/treatment target-related. Ten cases of UPC were used as controls. PSA was positive in 17% of SCPC and neuroendocrine markers were expressed in HGPC. PSA, TTF-1 and CD56 were the most helpful markers in differentiating between SCPC and HGPC (P<0.01), whereas bombesin/GRP, c-kit, bcl-2, and EGFR expression was more frequent in SCPC. SCPC is best diagnosed by following the World Health Organization diagnostic criteria for SCLC. Immunohistochemical markers can help separate SCPC from HGPC and may be useful in histologically borderline cases. Potential therapeutic targets are identified immunohistochemically in SCPC (Bombesin/GRP, c-kit, bcl-2, and EGFR).
Sean R Williamson - One of the best experts on this subject based on the ideXlab platform.
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frequent tmprss2 erg rearrangement in prostatic Small Cell Carcinoma detected by fluorescence in situ hybridization the superiority of fluorescence in situ hybridization over erg immunohistochemistry
Human Pathology, 2013Co-Authors: Lindsay A Schelling, Antonio Lopezbeltran, Sean R Williamson, Shaobo Zhang, Jorge L Yao, Mingsheng Wang, Jiaoti Huang, Rodolfo Montironi, Robert E Emerson, Muhammad T IdreesAbstract:Small Cell Carcinoma of the prostate is both morphologically and immunohistochemically similar to Small Cell Carcinoma of other organs such as the urinary bladder or lung. TMPRSS2-ERG gene fusion appears to be a highly specific alteration in prostatic Carcinoma that is frequently shared by Small Cell Carcinoma. In adenoCarcinoma, immunohistochemistry for the ERG protein product has been reported to correlate well with the presence of the gene fusion, although in prostatic Small Cell Carcinoma, this relationship is not completely understood. We evaluated 54 cases of Small Cell Carcinoma of the prostate and compared TMPRSS2-ERG gene fusion status by fluorescence in situ hybridization (FISH) to immunohistochemical staining with antibody to ERG. Of 54 cases of prostatic Small Cell Carcinoma, 26 (48%) were positive for TMPRSS2-ERG gene fusion by FISH and 12 (22%) showed overexpression of ERG protein by immunohistochemistry. Of the 26 cases positive by FISH, 11 were also positive for ERG protein by immunohistochemistry. One tumor was positive by immunohistochemistry but negative by FISH. Urinary bladder Small Cell Carcinoma (n = 25) showed negative results by both methods; however, 2 of 14 Small Cell Carcinomas of other organs (lung, head, and neck) showed positive immunohistochemistry but negative FISH. Positive staining for ERG by immunohistochemistry is present in a subset of prostatic Small Cell Carcinomas and correlates with the presence of TMPRSS2-ERG gene fusion. Therefore, it may be useful in confirming prostatic origin when molecular testing is not accessible. However, sensitivity and specificity of ERG immunohistochemistry in Small Cell Carcinoma are decreased compared to FISH.
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erg tmprss2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder evidence supporting monoclonal origin
Modern Pathology, 2011Co-Authors: Sean R Williamson, Gregory T Maclennan, Antonio Lopezbeltran, Shaobo Zhang, Jorge L Yao, Jiaoti Huang, Rodolfo Montironi, Steven S Shen, Adeboye O Osunkoya, Liang ChengAbstract:Prostatic Carcinoma is a heterogeneous disease with frequent multifocality and variability in morphology. Particularly, prostatic Small Cell Carcinoma is a rare variant with aggressive behavior. Distinction between Small Cell Carcinoma of the prostate and urinary bladder may be challenging, especially in Small biopsy specimens without associated prostatic adenoCarcinoma or urothelial Carcinoma. Recently, gene fusions between ETS genes, particularly ETS-related gene (ERG), and transmembrane protease, serine 2 (TMPRSS2) have been identified as a frequent event in prostate cancer. Thus, molecular methods may be helpful in determining the primary site of Small Cell Carcinoma. Thirty cases of prostatic Small Cell Carcinoma from the authors' archives were studied, among which 13 had concurrent prostatic adenoCarcinoma. Tricolor fluorescence in situ hybridization (FISH) was performed on formalin-fixed paraffin-embedded tissue sections with a probe cocktail for 3'/5' ERG and TMPRSS2. Cases of Small Cell Carcinoma of the bladder and conventional prostatic adenoCarcinoma (25 each) were also tested as controls. ERG gene alterations were found only in prostate malignancies and not in benign prostatic tissue or bladder Small Cell Carcinoma. TMPRSS2-ERG gene fusion was found in 47% (14/30) of prostatic Small Cell Carcinoma. Of cases with concurrent prostatic adenoCarcinoma, 85% (11/13) had identical findings in both components. In 20% of rearranged cases, the ERG abnormality was associated with 5' ERG deletion. In 17% (5/30) of cases, gain of the 21q22 locus was present. Two cases showed discordant aberrations in the Small Cell Carcinoma and adenoCarcinoma, one with deletion of 5' ERG and one with gain of chromosome 21q, both in only the adenoCarcinoma component. Small Cell Carcinoma of the prostate demonstrates TMPRSS2-ERG rearrangement with comparable frequency to prostatic adenoCarcinoma. In cases with concurrent adenoCarcinoma and Small Cell Carcinoma, the majority showed identical abnormalities in both components, indicating a likely common clonal origin. Discordant alterations were present in rare cases, suggesting that acquisition of additional genetic changes in multifocal tumors may be responsible for disease progression to a more aggressive phenotype. TMPRSS2-ERG fusion is absent in bladder Small Cell Carcinoma, supporting the utility of FISH in distinguishing prostate from bladder primary tumors and identifying metastatic Small Cell Carcinoma of unknown origin.
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erg tmprss2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder evidence supporting monoclonal origin
Modern Pathology, 2011Co-Authors: Sean R Williamson, Gregory T Maclennan, Antonio Lopezbeltran, Shaobo Zhang, Jiaoti Huang, Rodolfo Montironi, Steven S Shen, Adeboye O Osunkoya, Liang ChengAbstract:ERG–TMPRSS2 rearrangement is shared by concurrent prostatic adenoCarcinoma and prostatic Small Cell Carcinoma and absent in Small Cell Carcinoma of the urinary bladder: evidence supporting monoclonal origin
