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Reetesh K Pai - One of the best experts on this subject based on the ideXlab platform.
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loss of satb2 expression in Colorectal Carcinoma is associated with dna mismatch repair protein deficiency and braf mutation
The American Journal of Surgical Pathology, 2018Co-Authors: Dane C Olevian, Brett M Lowenthal, Priya Jayachandran, Margaret M Kozak, Daniel T Chang, Reetesh K PaiAbstract:The special AT-rich sequence binding protein (SATB2) has been reported to be a specific immunohistochemical marker for Colorectal Carcinoma; however, correlation of SATB2 expression with molecular alterations commonly assessed in Colorectal Carcinoma has not been performed. We examined the immunohistochemical expression of SATB2 in 586 adenoCarcinomas of the gastrointestinal (GI) tract and pancreas to assess its utility in diagnosis and analyze the clinicopathologic and molecular characteristics of Colorectal Carcinoma stratified by SATB2 expression. SATB2 and CDX2 expression were evaluated in 266 adenoCarcinomas of lower GI tract origin (246 Colorectal and 20 appendiceal mucinous), 208 adenoCarcinomas of upper GI tract and small intestinal origin (74 esophagus/esophagogastric junction, 103 stomach, 20 duodenal, and 11 jejunoileal), and 112 pancreatic ductal adenoCarcinomas. SATB2 expression was more frequently identified in adenoCarcinomas of lower GI tract origin (222/266, 83%) compared with upper GI tract, small intestinal, or pancreatic origin (26/320, 8%) (P<0.001). Compared with CDX2 alone, dual positive expression for SATB2 and CDX2 (SATB2/CDX2) has a significantly higher specificity for adenoCarcinoma of lower GI tract origin (94% vs. 57%, P<0.001). In Colorectal Carcinoma, loss of SATB2 expression was more frequently observed in DNA mismatch repair (MMR) protein deficient tumors (31%) compared with MMR protein proficient tumors (13%) (P<0.01). A BRAF V600E mutation was more frequently identified in Colorectal Carcinomas with loss of SATB2 expression compared with those with positive SATB2 expression (29% vs. 3%) (P<0.001). In summary, SATB2 expression is a relatively specific marker of lower GI tract origin; however, loss of SATB2 expression is more commonly seen in Colorectal Carcinoma with MMR protein deficiency and BRAF mutation.
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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.
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.
Daniel T Chang - One of the best experts on this subject based on the ideXlab platform.
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loss of satb2 expression in Colorectal Carcinoma is associated with dna mismatch repair protein deficiency and braf mutation
The American Journal of Surgical Pathology, 2018Co-Authors: Dane C Olevian, Brett M Lowenthal, Priya Jayachandran, Margaret M Kozak, Daniel T ChangAbstract:The special AT-rich sequence binding protein (SATB2) has been reported to be a specific immunohistochemical marker for Colorectal Carcinoma; however, correlation of SATB2 expression with molecular alterations commonly assessed in Colorectal Carcinoma has not been performed. We examined the immunohis
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loss of satb2 expression in Colorectal Carcinoma is associated with dna mismatch repair protein deficiency and braf mutation
The American Journal of Surgical Pathology, 2018Co-Authors: Dane C Olevian, Brett M Lowenthal, Priya Jayachandran, Margaret M Kozak, Daniel T Chang, Reetesh K PaiAbstract:The special AT-rich sequence binding protein (SATB2) has been reported to be a specific immunohistochemical marker for Colorectal Carcinoma; however, correlation of SATB2 expression with molecular alterations commonly assessed in Colorectal Carcinoma has not been performed. We examined the immunohistochemical expression of SATB2 in 586 adenoCarcinomas of the gastrointestinal (GI) tract and pancreas to assess its utility in diagnosis and analyze the clinicopathologic and molecular characteristics of Colorectal Carcinoma stratified by SATB2 expression. SATB2 and CDX2 expression were evaluated in 266 adenoCarcinomas of lower GI tract origin (246 Colorectal and 20 appendiceal mucinous), 208 adenoCarcinomas of upper GI tract and small intestinal origin (74 esophagus/esophagogastric junction, 103 stomach, 20 duodenal, and 11 jejunoileal), and 112 pancreatic ductal adenoCarcinomas. SATB2 expression was more frequently identified in adenoCarcinomas of lower GI tract origin (222/266, 83%) compared with upper GI tract, small intestinal, or pancreatic origin (26/320, 8%) (P<0.001). Compared with CDX2 alone, dual positive expression for SATB2 and CDX2 (SATB2/CDX2) has a significantly higher specificity for adenoCarcinoma of lower GI tract origin (94% vs. 57%, P<0.001). In Colorectal Carcinoma, loss of SATB2 expression was more frequently observed in DNA mismatch repair (MMR) protein deficient tumors (31%) compared with MMR protein proficient tumors (13%) (P<0.01). A BRAF V600E mutation was more frequently identified in Colorectal Carcinomas with loss of SATB2 expression compared with those with positive SATB2 expression (29% vs. 3%) (P<0.001). In summary, SATB2 expression is a relatively specific marker of lower GI tract origin; however, loss of SATB2 expression is more commonly seen in Colorectal Carcinoma with MMR protein deficiency and BRAF mutation.
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lef 1 is frequently expressed in Colorectal Carcinoma and not in other gastrointestinal tract adenoCarcinomas an immunohistochemical survey of 602 gastrointestinal tract neoplasms
Applied Immunohistochemistry & Molecular Morphology, 2014Co-Authors: Taher Reza Kermanshahi, Priya Jayachandran, Daniel T Chang, Reet PaiAbstract:LEF-1 is a DNA-binding protein that interacts with β-catenin and activates Wnt-responsive target genes. We analyzed the immunohistochemical expression of LEF-1 in 602 gastrointestinal and pancreatobiliary neoplasms in an attempt to (1) investigate the utility of LEF-1 immunohistochemistry as an ancillary marker in gastrointestinal/pancreatobiliary neoplasia, and (2) to perform a clinicopathologic and survival analysis of Colorectal Carcinoma stratified by LEF-1 expression. LEF-1 nuclear positivity was frequently identified in Colorectal Carcinoma (89/241, 37%) and only infrequently identified in other neoplasms: 11% esophagus/esophagogastric adenoCarcinomas, 7% gastric adenoCarcinomas, 1% pancreatic ductal adenoCarcinomas, 4% pancreatic intraductal papillary mucinous neoplasms, and in no cases of appendiceal mucinous neoplasms or pancreatic mucinous cystic neoplasms. LEF-1 expression was identified in 35% of Colorectal Carcinomas that lacked CK20 and CDX2 expression. In Colorectal Carcinomas, LEF-1-positive tumors more frequently harbored KRAS mutations compared with LEF-1-negative tumors (39% vs. 16%, P=0.005). Patients with moderate/strong LEF-1-positive Colorectal Carcinoma had a trend of worse overall survival compared with patients with Colorectal Carcinomas with weak/negative LEF-1 expression (5 y overall survival, 31% vs. 47%, P=0.15). In conclusion, LEF-1 is most commonly expressed in Colorectal Carcinoma and infrequently observed in the upper gastrointestinal tract and pancreatic adenoCarcinoma. LEF-1 Immunohistochemistry may be especially useful as an ancillary diagnostic marker in Colorectal Carcinomas, which lack the expression of both CK20 and CDX2. LEF-1 expression is associated with the presence of KRAS mutations and may have prognostic value as a trend of worse overall survival is seen in patients with LEF-1-positive Colorectal Carcinoma.
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.
Dane C Olevian - One of the best experts on this subject based on the ideXlab platform.
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loss of satb2 expression in Colorectal Carcinoma is associated with dna mismatch repair protein deficiency and braf mutation
The American Journal of Surgical Pathology, 2018Co-Authors: Dane C Olevian, Brett M Lowenthal, Priya Jayachandran, Margaret M Kozak, Daniel T ChangAbstract:The special AT-rich sequence binding protein (SATB2) has been reported to be a specific immunohistochemical marker for Colorectal Carcinoma; however, correlation of SATB2 expression with molecular alterations commonly assessed in Colorectal Carcinoma has not been performed. We examined the immunohis
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loss of satb2 expression in Colorectal Carcinoma is associated with dna mismatch repair protein deficiency and braf mutation
The American Journal of Surgical Pathology, 2018Co-Authors: Dane C Olevian, Brett M Lowenthal, Priya Jayachandran, Margaret M Kozak, Daniel T Chang, Reetesh K PaiAbstract:The special AT-rich sequence binding protein (SATB2) has been reported to be a specific immunohistochemical marker for Colorectal Carcinoma; however, correlation of SATB2 expression with molecular alterations commonly assessed in Colorectal Carcinoma has not been performed. We examined the immunohistochemical expression of SATB2 in 586 adenoCarcinomas of the gastrointestinal (GI) tract and pancreas to assess its utility in diagnosis and analyze the clinicopathologic and molecular characteristics of Colorectal Carcinoma stratified by SATB2 expression. SATB2 and CDX2 expression were evaluated in 266 adenoCarcinomas of lower GI tract origin (246 Colorectal and 20 appendiceal mucinous), 208 adenoCarcinomas of upper GI tract and small intestinal origin (74 esophagus/esophagogastric junction, 103 stomach, 20 duodenal, and 11 jejunoileal), and 112 pancreatic ductal adenoCarcinomas. SATB2 expression was more frequently identified in adenoCarcinomas of lower GI tract origin (222/266, 83%) compared with upper GI tract, small intestinal, or pancreatic origin (26/320, 8%) (P<0.001). Compared with CDX2 alone, dual positive expression for SATB2 and CDX2 (SATB2/CDX2) has a significantly higher specificity for adenoCarcinoma of lower GI tract origin (94% vs. 57%, P<0.001). In Colorectal Carcinoma, loss of SATB2 expression was more frequently observed in DNA mismatch repair (MMR) protein deficient tumors (31%) compared with MMR protein proficient tumors (13%) (P<0.01). A BRAF V600E mutation was more frequently identified in Colorectal Carcinomas with loss of SATB2 expression compared with those with positive SATB2 expression (29% vs. 3%) (P<0.001). In summary, SATB2 expression is a relatively specific marker of lower GI tract origin; however, loss of SATB2 expression is more commonly seen in Colorectal Carcinoma with MMR protein deficiency and BRAF mutation.