Monday, January 20, 2014

Cadherin-17 and SATB2 Are Sensitive and Specific Immunomarkers for Medullary Carcinoma of the Large Intestine

Fan Lin MD, PhDJianhui Shi MD, PhDShaobo Zhu MDZongming Chen MD, PhDAihua Li MD, PhDTaiying Chen PhD;Hanlin L Wang MD, PhDHaiyan Liu MD
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).
Context.—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.
Design.—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.

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