Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary carcinoma of the large intestine.
BACKGROUND
Distinction of medullary carcinoma of the large intestine from other cytokeratin (CK) 7⁻/CK20⁻ carcinomas can be challenging when working on a tumor of unknown primary because the majority of medullary carcinomas are negative for CK7, CK20, and CDX2.


OBJECTIVE
To investigate the expression of cadherin-17 and SATB-2 and other markers in medullary carcinomas of the large intestine and cadherin-17 and SATB2 in a large number of carcinomas and normal tissues from various organs to further test their diagnostic specificity.


METHODS
This study evaluated cadherin-17 and SATB2 expression in 18 medullary carcinoma cases and 1941 tumors and 358 normal tissues from various organs. Other immunomarkers, including MLH1, PMS2, MSH2, MSH6, CDX2, CK7, CK20, TFF3, MUC4, calretinin, p504S, villin, and synaptophysin, were also tested on the 18 medullary carcinoma cases.


RESULTS
The results demonstrated (1) loss of MLH1 and PMS2 in more than 80% of medullary carcinomas; (2) expression of cadherin-17 and SATB2 in 89% of medullary carcinomas; (3) focal expression of TFF3, MUC4, calretinin, CDX2, CK20, and synaptophysin in 72%, 72%, 67%, 67%, 28%, and 17% of 18 medullary carcinoma cases, respectively; and (4) expression of SATB2 and cadherin-17 in 97% and 98% of the colorectal adenocarcinomas, respectively, whereas their expression was seen in 3.6% and 3.3% of nongastrointestinal tumors, respectively.


CONCLUSIONS
We concluded that SATB2 and cadherin-17 were highly sensitive and specific markers for colorectal carcinomas and propose including MLH1, cadherin-17, and SATB2 in a routine immunostaining panel when working on a tumor of unknown primary, especially in an elderly patient with a CK7⁻/CK20⁻ carcinoma.
From the Department of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania (Drs. Lin, Shi, Zhu, Z. Chen, and Liu); the Division of In Vitro Diagnostics, Epitomics, Inc, an Abcam Company, Burlingame, California (Drs Li and T. Chen); and the Department of Pathology, University of California, Los Angeles (Dr Wang).
Fan
F
Lin
Jianhui
J
Shi
Shaobo
S
Zhu
Zongming
Z
Chen
Aihua
A
Li
Taiying
T
Chen
Hanlin L
HL
Wang
Haiyan
H
Liu
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D018276:Carcinoma, Medullary / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D002430:Cecal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D002432:Cecum / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism*; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism*; D047368:Tumor Burden
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; C490584:CDH17 protein, human; D015820:Cadherins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D036961:Matrix Attachment Region Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C521297:SATB2 protein, human; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes