TY - JOUR
T1 - Optimization of immunophenotypic panel to differentiate upper from lower gastrointestinal adenocarcinomas
T2 - Analysis of new and traditional markers
AU - Chauhan, Aastha
AU - Sanchez-Avila, Monica
AU - Manivel, Juan
AU - Dachel, Susan
AU - Larson, Wendy
AU - Hanson, Brian
AU - Gravely, Amy
AU - Mesa, Hector
N1 - Publisher Copyright:
© 2020 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - Adenocarcinomas of the esophagus (EAC), stomach [gastric adenocarcinoma (GAC)], and colorectal carcinoma (CRC) frequently show similar morphology because upper gastrointestinal tumors (GITs) usually evolve from pathologies involving intestinal metaplasia. Upper and lower GIT may also show overlapping immunophenotypes when using the traditional CK7, CK20, and CDX2 panel, which in patients presenting with metastatic disease of unknown origin may lead to misdirected diagnostic workup and/or therapy. We compared the phenotype of upper and lower GIT using an expanded immunohistochemical panel that included the traditional and newer gastrointestinal markers: SATB2, DcR3, MUC5AC, and MUC6. The panel was applied to resection specimens from 40 CRC, 40 GAC, and 40 EAC. A panel using SATB2, CK7, and CDX2 provided the best discriminating power for separating upper from lower GIT and was applied to 101 biopsies including 17 EAC, 17 GAC, 19 CRC, 18 pancreatic adenocarcinomas, 15 cholangiocarcinomas, and 15 lung adenocarcinomas. The phenotype CK7+/CDX2+/SATB2- was moderately sensitive and highly specific of upper GIT, the phenotype CK7-/CDX2+/SATB2+ was highly sensitive and specific for lower GIT, the phenotypes CK7+/CDX2-/SATB2- and CK7+/CDX2-/SATB2+ favored pancreatobiliary or lung primaries. Less frequent phenotypes showed substantial overlap. Although strong diffuse expression of SATB2 was characteristic of CRC, weak and/or focal expression was present in one third or more of upper gastrointestinal, cholangiocarcinomas, and lung adenocarcinomas. DcR3, MUC5AC, and MUC6 improved specificity, but showed poor sensitivity, suggesting they should be used as second tier markers.
AB - Adenocarcinomas of the esophagus (EAC), stomach [gastric adenocarcinoma (GAC)], and colorectal carcinoma (CRC) frequently show similar morphology because upper gastrointestinal tumors (GITs) usually evolve from pathologies involving intestinal metaplasia. Upper and lower GIT may also show overlapping immunophenotypes when using the traditional CK7, CK20, and CDX2 panel, which in patients presenting with metastatic disease of unknown origin may lead to misdirected diagnostic workup and/or therapy. We compared the phenotype of upper and lower GIT using an expanded immunohistochemical panel that included the traditional and newer gastrointestinal markers: SATB2, DcR3, MUC5AC, and MUC6. The panel was applied to resection specimens from 40 CRC, 40 GAC, and 40 EAC. A panel using SATB2, CK7, and CDX2 provided the best discriminating power for separating upper from lower GIT and was applied to 101 biopsies including 17 EAC, 17 GAC, 19 CRC, 18 pancreatic adenocarcinomas, 15 cholangiocarcinomas, and 15 lung adenocarcinomas. The phenotype CK7+/CDX2+/SATB2- was moderately sensitive and highly specific of upper GIT, the phenotype CK7-/CDX2+/SATB2+ was highly sensitive and specific for lower GIT, the phenotypes CK7+/CDX2-/SATB2- and CK7+/CDX2-/SATB2+ favored pancreatobiliary or lung primaries. Less frequent phenotypes showed substantial overlap. Although strong diffuse expression of SATB2 was characteristic of CRC, weak and/or focal expression was present in one third or more of upper gastrointestinal, cholangiocarcinomas, and lung adenocarcinomas. DcR3, MUC5AC, and MUC6 improved specificity, but showed poor sensitivity, suggesting they should be used as second tier markers.
KW - Differential diagnosis
KW - Gastrointestinal
KW - Immunohistochemistry
KW - Immunophenotyping
KW - Neoplasms
UR - http://www.scopus.com/inward/record.url?scp=85097968072&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097968072&partnerID=8YFLogxK
U2 - 10.1097/PAI.0000000000000831
DO - 10.1097/PAI.0000000000000831
M3 - Article
C2 - 33295746
AN - SCOPUS:85097968072
SN - 1541-2016
VL - 29
SP - 13
EP - 19
JO - Applied Immunohistochemistry and Molecular Morphology
JF - Applied Immunohistochemistry and Molecular Morphology
IS - 1
ER -