Abstract

A subset (10-12%) of lung adenocarcinomas may express the gastrointestinal marker CDX-2 making the distinction between metastatic colorectal adenocarcinomas and primary lung adenocarcinoma difficult. Special AT-rich sequence-binding protein 2 (SATB2) was recently identified as a highly specific marker of the glandular epithelium lining the lower GI tract. SATB2 expression is retained in the large majority of colorectal adenocarcinomas (85-97%) and is only uncommonly expressed in esophageal (6.7%), gastric (0%) and pancreas (4.2%) adenocarcinomas. There is only very limited data available regarding SATB2 expression in lung adenocarcinomas. Here we report our findings on SATB2 expression in 92 cases of lung adenocarcinomas lacking intestinal differentiation and with known CDX-2 expression status. Four (4) micron sections of previously constructed tissue microarrays (TMA) containing 92 cases of lung adenocarcinomas were subjected to immunohistochemistry for TTF-1, Napsin A, p40, CDX-2 and SATB2 using an autostainer and commercially available monoclonal antibodies. Tumors showing staining of any intensity (for SATB2 and CDX-2) in greater than 5% of the tumor cells were accepted as positive. The cohort consisted of 13 well, 52 moderately and 27 poorly differentiated adenocarcinomas. Eighty-one tumor was positive for at least one adenocarcinoma marker with 68 tumors showing staining for both TTF-1 and napsin A, while p40 was negative in all cases. Positive CDX-2 staining was seen in 9 tumors (10%), while positive SATB2 staining was seen in only one tumor (1%). Focal (<5%) SATB2 staining was noted in 3 additional tumors. SATB2 is a novel marker that is highly specific for colorectal adenocarcinomas and appears to be rarely expressed in primary lung adenocarcinoma. On the other hand, CDX-2, a widely used marker of gastrointestinal adenocarcinoma is expressed in a subset of primary lung adenocarcinomas (10% in the current study) making the distinction between primary lung adenocarcinoma and metastatic colorectal adenocarcinoma difficult, especially in small biopsies where we rely more on immunohistochemistry to render a more specific diagnosis. SATB2 appears to be a promising marker that is superior to CDX-2 for distinguishing between primary lung adenocarcinoma and tumors of the lower gastrointestinal tract.

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