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Reetesh K Pai - One of the best experts on this subject based on the ideXlab platform.
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braf mutated microsatellite stable colorectal Carcinoma an aggressive adenoCarcinoma with reduced cdx2 and increased cytokeratin 7 immunohistochemical expression
Human Pathology, 2014Co-Authors: Michael S Landau, Shihfan Kuan, Simion I Chiosea, Reetesh K PaiAbstract:Reduced CDX2 and cytokeratin 20 (CK20) expression in colorectal Carcinoma with BRAF mutation and high-level microsatellite instability (MSI-H) has been well documented. The immunophenotype of BRAF-mutated microsatellite stable (MSS) colorectal Carcinoma has not been reported. We analyzed 205 colorectal Carcinomas including 28 BRAF-mutated MSS, 53 BRAF-mutated MSI-H, and 124 BRAF wild-type MSS tumors for CDX2, cytokeratin 7 (CK7), and CK20 immunohistochemical expression. CDX2 was scored semiquantitatively for both staining intensity and percent of tumor cells staining and a modified CDX2 H-score was calculated. Patients with BRAF-mutated MSS colorectal Carcinomas were more frequently stage IV at presentation compared to patients with BRAF-mutated MSI-H colorectal Carcinomas and BRAF wild-type MSS colorectal Carcinomas (32% versus 8% versus 15%, P < .001). BRAF-mutated MSS colorectal Carcinoma displayed reduced CDX2 expression compared to BRAF wild-type MSS colorectal Carcinoma (75% versus 94%; mean CDX2 H-score 98 versus 150, P < .001). CK7 expression was more often identified in BRAF-mutated MSS colorectal Carcinoma compared to both BRAF-mutated MSI-H colorectal Carcinoma and BRAF wild-type MSS colorectal Carcinoma (39% versus 6% versus 6%, P = .0001). BRAF-mutated MSI-H colorectal Carcinomas were less often CK20 positive compared to BRAF-mutated MSS and BRAF wild-type MSS tumors (70% versus 93% versus 90%, P = 0.001). In summary, BRAF-mutated MSS colorectal Carcinoma often displays reduced CDX2 and increased CK7 expression. Knowledge of this altered immunophenotype is important as patients with BRAF-mutated MSS colorectal Carcinoma often present with metastatic disease and the altered tumor immunophenotype may lead to the erroneous assumption that origin from the colon/rectum is unlikely.
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signet ring cell colorectal Carcinoma a distinct subset of mucin poor microsatellite stable signet ring cell Carcinoma associated with dismal prognosis
The American Journal of Surgical Pathology, 2013Co-Authors: Douglas J Hartman, Marina N Nikiforova, Daniel T Chang, Edward Chu, Nathan Bahary, Randall E Brand, Amer H Zureikat, Herbert J Zeh, Haroon A Choudry, Reetesh K PaiAbstract:We evaluated a consecutive series of signet ring cell colorectal Carcinomas in an attempt to correlate the histopathologic pattern of infiltration with molecular alterations and prognosis. Of the 4760 primary colorectal Carcinomas surgically resected between the years 2002 and 2012, 53 (1%) were composed of >50% signet ring cells. Of the 53 signet ring cell Carcinomas, 40 (75%) were composed of >50% extracellular mucin with signet ring cells floating within pools of mucin and were subclassified as mucin-rich signet ring cell Carcinomas. Thirteen (25%) Carcinomas were characterized by diffusely infiltrating Carcinomas with minimal to no extracellular mucin and were subclassified as mucin-poor signet ring cell Carcinomas. All 13 mucin-poor signet ring cell Carcinomas were either stage III or IV, whereas many cases of mucin-rich signet ring cell Carcinoma were stage I or II (17 cases) (P=0.005). Compared with mucin-rich tumors, mucin-poor signet ring cell Carcinomas more frequently demonstrated adverse histologic features such as lymphatic invasion (13/13, 100% vs. 22/40, 55%; P=0.002), venous invasion (6/13, 46% vs. 3/40, 8%; P=0.004), and perineural invasion (11/13, 85% vs. 9/40, 23%; P=0.0001). Twenty-three of 53 (43%) signet ring cell Carcinomas demonstrated high levels of microsatellite instability (MSI-H). Twenty-two of 23 (96%) MSI-H signet ring cell Carcinomas were mucin rich; only 1 MSI-H signet ring Carcinoma was mucin poor (P=0.0033). Mucin-poor signet ring cell Carcinoma had significantly reduced overall and recurrence-free survival compared with mucin-rich signet ring cell Carcinomas (P=0.0035 and 0.0001, respectively), even when adjusting for tumor stage. Mucin-poor signet ring cell Carcinoma had a higher propensity for peritoneal dissemination (5/13, 38%) compared with mucin-rich signet ring cell Carcinoma (5/40, 12.5%), although this was not statistically significant (P=0.052). Finally, MSI-H and microsatellite-stable signet ring cell Carcinomas had similar overall and recurrence-free survival (P=0.2266 and 0.1055, respectively), even when adjusting for tumor stage. In conclusion, we identified a unique subset of signet ring cell colorectal Carcinoma with diffuse infiltration and minimal to no extracellular mucin (mucin-poor signet ring cell Carcinoma), which lacks MSI-H and has a dismal prognosis with an aggressive clinical course often with peritoneal dissemination. Further, our results confirm that MSI does not affect survival in colorectal signet ring cell Carcinomas.
Simion I Chiosea - One of the best experts on this subject based on the ideXlab platform.
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braf mutated microsatellite stable colorectal Carcinoma an aggressive adenoCarcinoma with reduced cdx2 and increased cytokeratin 7 immunohistochemical expression
Human Pathology, 2014Co-Authors: Michael S Landau, Shihfan Kuan, Simion I ChioseaAbstract:Summary Reduced CDX2 and cytokeratin 20 (CK20) expression in colorectal Carcinoma with BRAF mutation and high-level microsatellite instability (MSI-H) has been well documented. The immunophenotype of BRAF- mutated microsatellite stable (MSS) colorectal Carcinoma has not been reported. We analyzed 205 colorectal Carcinomas including 28 BRAF -mutated MSS, 53 BRAF -mutated MSI-H, and 124 BRAF wild-type MSS tumors for CDX2, cytokeratin 7 (CK7), and CK20 immunohistochemical expression. CDX2 was scored semiquantitatively for both staining intensity and percent of tumor cells staining and a modified CDX2 H-score was calculated. Patients with BRAF -mutated MSS colorectal Carcinomas were more frequently stage IV at presentation compared to patients with BRAF -mutated MSI-H colorectal Carcinomas and BRAF wild-type MSS colorectal Carcinomas (32% versus 8% versus 15%, P BRAF -mutated MSS colorectal Carcinoma displayed reduced CDX2 expression compared to BRAF wild-type MSS colorectal Carcinoma (75% versus 94%; mean CDX2 H-score 98 versus 150, P BRAF -mutated MSS colorectal Carcinoma compared to both BRAF -mutated MSI-H colorectal Carcinoma and BRAF wild-type MSS colorectal Carcinoma (39% versus 6% versus 6%, P = .0001). BRAF -mutated MSI-H colorectal Carcinomas were less often CK20 positive compared to BRAF -mutated MSS and BRAF wild-type MSS tumors (70% versus 93% versus 90%, P = 0.001). In summary, BRAF -mutated MSS colorectal Carcinoma often displays reduced CDX2 and increased CK7 expression. Knowledge of this altered immunophenotype is important as patients with BRAF -mutated MSS colorectal Carcinoma often present with metastatic disease and the altered tumor immunophenotype may lead to the erroneous assumption that origin from the colon/rectum is unlikely.
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braf mutated microsatellite stable colorectal Carcinoma an aggressive adenoCarcinoma with reduced cdx2 and increased cytokeratin 7 immunohistochemical expression
Human Pathology, 2014Co-Authors: Michael S Landau, Shihfan Kuan, Simion I Chiosea, Reetesh K PaiAbstract:Reduced CDX2 and cytokeratin 20 (CK20) expression in colorectal Carcinoma with BRAF mutation and high-level microsatellite instability (MSI-H) has been well documented. The immunophenotype of BRAF-mutated microsatellite stable (MSS) colorectal Carcinoma has not been reported. We analyzed 205 colorectal Carcinomas including 28 BRAF-mutated MSS, 53 BRAF-mutated MSI-H, and 124 BRAF wild-type MSS tumors for CDX2, cytokeratin 7 (CK7), and CK20 immunohistochemical expression. CDX2 was scored semiquantitatively for both staining intensity and percent of tumor cells staining and a modified CDX2 H-score was calculated. Patients with BRAF-mutated MSS colorectal Carcinomas were more frequently stage IV at presentation compared to patients with BRAF-mutated MSI-H colorectal Carcinomas and BRAF wild-type MSS colorectal Carcinomas (32% versus 8% versus 15%, P < .001). BRAF-mutated MSS colorectal Carcinoma displayed reduced CDX2 expression compared to BRAF wild-type MSS colorectal Carcinoma (75% versus 94%; mean CDX2 H-score 98 versus 150, P < .001). CK7 expression was more often identified in BRAF-mutated MSS colorectal Carcinoma compared to both BRAF-mutated MSI-H colorectal Carcinoma and BRAF wild-type MSS colorectal Carcinoma (39% versus 6% versus 6%, P = .0001). BRAF-mutated MSI-H colorectal Carcinomas were less often CK20 positive compared to BRAF-mutated MSS and BRAF wild-type MSS tumors (70% versus 93% versus 90%, P = 0.001). In summary, BRAF-mutated MSS colorectal Carcinoma often displays reduced CDX2 and increased CK7 expression. Knowledge of this altered immunophenotype is important as patients with BRAF-mutated MSS colorectal Carcinoma often present with metastatic disease and the altered tumor immunophenotype may lead to the erroneous assumption that origin from the colon/rectum is unlikely.
Michael S Landau - One of the best experts on this subject based on the ideXlab platform.
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braf mutated microsatellite stable colorectal Carcinoma an aggressive adenoCarcinoma with reduced cdx2 and increased cytokeratin 7 immunohistochemical expression
Human Pathology, 2014Co-Authors: Michael S Landau, Shihfan Kuan, Simion I ChioseaAbstract:Summary Reduced CDX2 and cytokeratin 20 (CK20) expression in colorectal Carcinoma with BRAF mutation and high-level microsatellite instability (MSI-H) has been well documented. The immunophenotype of BRAF- mutated microsatellite stable (MSS) colorectal Carcinoma has not been reported. We analyzed 205 colorectal Carcinomas including 28 BRAF -mutated MSS, 53 BRAF -mutated MSI-H, and 124 BRAF wild-type MSS tumors for CDX2, cytokeratin 7 (CK7), and CK20 immunohistochemical expression. CDX2 was scored semiquantitatively for both staining intensity and percent of tumor cells staining and a modified CDX2 H-score was calculated. Patients with BRAF -mutated MSS colorectal Carcinomas were more frequently stage IV at presentation compared to patients with BRAF -mutated MSI-H colorectal Carcinomas and BRAF wild-type MSS colorectal Carcinomas (32% versus 8% versus 15%, P BRAF -mutated MSS colorectal Carcinoma displayed reduced CDX2 expression compared to BRAF wild-type MSS colorectal Carcinoma (75% versus 94%; mean CDX2 H-score 98 versus 150, P BRAF -mutated MSS colorectal Carcinoma compared to both BRAF -mutated MSI-H colorectal Carcinoma and BRAF wild-type MSS colorectal Carcinoma (39% versus 6% versus 6%, P = .0001). BRAF -mutated MSI-H colorectal Carcinomas were less often CK20 positive compared to BRAF -mutated MSS and BRAF wild-type MSS tumors (70% versus 93% versus 90%, P = 0.001). In summary, BRAF -mutated MSS colorectal Carcinoma often displays reduced CDX2 and increased CK7 expression. Knowledge of this altered immunophenotype is important as patients with BRAF -mutated MSS colorectal Carcinoma often present with metastatic disease and the altered tumor immunophenotype may lead to the erroneous assumption that origin from the colon/rectum is unlikely.
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braf mutated microsatellite stable colorectal Carcinoma an aggressive adenoCarcinoma with reduced cdx2 and increased cytokeratin 7 immunohistochemical expression
Human Pathology, 2014Co-Authors: Michael S Landau, Shihfan Kuan, Simion I Chiosea, Reetesh K PaiAbstract:Reduced CDX2 and cytokeratin 20 (CK20) expression in colorectal Carcinoma with BRAF mutation and high-level microsatellite instability (MSI-H) has been well documented. The immunophenotype of BRAF-mutated microsatellite stable (MSS) colorectal Carcinoma has not been reported. We analyzed 205 colorectal Carcinomas including 28 BRAF-mutated MSS, 53 BRAF-mutated MSI-H, and 124 BRAF wild-type MSS tumors for CDX2, cytokeratin 7 (CK7), and CK20 immunohistochemical expression. CDX2 was scored semiquantitatively for both staining intensity and percent of tumor cells staining and a modified CDX2 H-score was calculated. Patients with BRAF-mutated MSS colorectal Carcinomas were more frequently stage IV at presentation compared to patients with BRAF-mutated MSI-H colorectal Carcinomas and BRAF wild-type MSS colorectal Carcinomas (32% versus 8% versus 15%, P < .001). BRAF-mutated MSS colorectal Carcinoma displayed reduced CDX2 expression compared to BRAF wild-type MSS colorectal Carcinoma (75% versus 94%; mean CDX2 H-score 98 versus 150, P < .001). CK7 expression was more often identified in BRAF-mutated MSS colorectal Carcinoma compared to both BRAF-mutated MSI-H colorectal Carcinoma and BRAF wild-type MSS colorectal Carcinoma (39% versus 6% versus 6%, P = .0001). BRAF-mutated MSI-H colorectal Carcinomas were less often CK20 positive compared to BRAF-mutated MSS and BRAF wild-type MSS tumors (70% versus 93% versus 90%, P = 0.001). In summary, BRAF-mutated MSS colorectal Carcinoma often displays reduced CDX2 and increased CK7 expression. Knowledge of this altered immunophenotype is important as patients with BRAF-mutated MSS colorectal Carcinoma often present with metastatic disease and the altered tumor immunophenotype may lead to the erroneous assumption that origin from the colon/rectum is unlikely.
Massimo Loda - One of the best experts on this subject based on the ideXlab platform.
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distinct molecular features of colorectal Carcinoma with signet ring cell component and colorectal Carcinoma with mucinous component
Modern Pathology, 2006Co-Authors: Shuji Ogino, Jeffrey A Meyerhardt, Mohan Brahmandam, Mami Cantor, Chungdak Namgyal, Takako Kawasaki, Gregory J Kirkner, Massimo LodaAbstract:Signet ring cell Carcinoma and mucinous Carcinoma are distinct subtypes of colorectal adenoCarcinoma. The morphologic and molecular spectra of colorectal Carcinomas with various signet ring cell components and colorectal Carcinomas with various mucinous components, compared to non-mucinous adenoCarcinomas, have not been examined. The study groups consisted of 39 Carcinomas with various signet ring cell components ('the signet group'), 167 Carcinomas with various mucinous components ('the mucinous group'), and 457 nonmucinous adenoCarcinoma. We visually estimated the amounts of signet ring cell and mucinous components in tumors, and subclassified the signet and mucinous groups according to the amount of each component ( or = 50%). We sequenced BRAF and KRAS, analyzed for microsatellite instability (MSI) and 18q loss of heterozygosity (LOH), and performed immunohistochemistry for TP53, cyclooxygenase-2 (COX2), MLH1, O-6-methylguanine DNA methyltransferase (MGMT), p16 (CDKN2A), and fatty acid synthase (FASN). Signet ring cell Carcinoma (> or = 50% signet ring cell tumors) and or = 50% mucinous tumors and or = 50% signet ring cell or mucinous Carcinoma, respectively. Signet ring cell Carcinoma and mucinous Carcinoma are related subtypes of colorectal adenoCarcinoma, but have molecular features distinct from each other.
Preetha Ramalingam - One of the best experts on this subject based on the ideXlab platform.
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immunohistochemical expression of pax5 and tdt by merkel cell Carcinoma and pulmonary small cell Carcinoma a potential diagnostic pitfall but useful discriminatory marker
International Journal of Clinical and Experimental Pathology, 2013Co-Authors: Ravindra Kolhe, Michelle D Reid, Jeffrey R Lee, Cynthia Cohen, Preetha RamalingamAbstract:Background: Merkel cell Carcinoma is a high-grade neuroendocrine Carcinoma of skin that is characterized by immature cells which, because of its striking morphologic similarity, may be confused with other small round blue cell tumors such as pulmonary small cell Carcinoma or lymphoblastic leukemia/lymphoma. Immunohistochemistry is therefore paramount to ensuring accurate diagnostic distinction between these tumors. The aim of our study was to evaluate and compare the expression of PAX5 and Terminal deoxynucleotidyl transferase (TdT), in Merkel cell Carcinoma and pulmonary small cell Carcinoma. Design: PAX5 and TdT immunohistochemical stains were performed on 27 Merkel cell Carcinomas and 10 pulmonary small cell Carcinomas. Results: PAX5 was expressed in 24/27 (89%) Merkel cell Carcinomas and 0/10 (0%) pulmonary small cell Carcinomas. TdT was expressed in 21/27 (78%) Merkel cell Carcinomas and 9/10 (90%) pulmonary small cell Carcinomas. Conclusions: Our study confirms that PAX5 and TdT expression can be expressed in a high percentage of Merkel cell Carcinomas and so when positive are not diagnostic of lymphoblastic leukemia/lymphoma. When dealing with metastatic lesions, PAX5 negativity would favor a diagnosis of pulmonary small cell Carcinoma over Merkel cell Carcinoma. In addition, TTF-1 negative pulmonary small cell Carcinoma is to be differentiated from Merkel cell Carcinoma.
