Cytokeratin 7 and 20 and thyroid transcription factor 1 can help distinguish pulmonary from gastrointestinal carcinoid and pancreatic endocrine tumors

Expression of cytokeratin (CK) 7 and 20 is commonly used to help distinguis h adenocarcinomas from different sites. Thyroid transcription factor I (TTF -l) is a 38-kd protein, located primarily in the nucleus of type 2 pneumocy tes and clara cells. TTF-1 has been shown to be present in a variety of lun g and thyroid tumors and in pulmonary small-cell carcinomas. Carcinoid tumo rs from the lung and the gastrointestinal (Gl) tract are histologically sim ilar and thus are difficult to differentiate from each other based on histo logic criteria. Pancreatic endocrine tumors (PET) have a similar histologic appearance to these other tumors. The purpose of this study was to determi ne the efficacy of differentiating these 3 groups of tumors by their expres sion of CK7, CK20, and TTF-1. Routinely processed paraffin-embedded tissue sections from 62 carcinoid tumors (lung, 16; gastrointestinal [GI] tract, 4 6) and 12 PETs were immunohistochemically stained for CK7, CK20, and TTF-1. The degree of expression in each tumor was graded as 1+ (1% to 10% of cell s positive), 2+ (11% to 25%), 3+ (26% to 50%), and 4+ (> 50%). The data wer e compared between tumor types and between carcinoid tumors from the variou s locations in the GI tract (stomach, 8; small intestine, 19; large intesti ne, 17; appendix, 2). CK7 was expressed in 10 (63%) of 16 pulmonary carcino id tumors and only 5 (11%) of 46 GI carcinoid tumors (P < .001). Pancreatic endocrine tumors showed CK7 positivity in 6 (50%) of 12 cases, which was s imilar to the findings in lung carcinoids and significantly higher than in GI carcinoids (P < .01). CK20 was expressed in 0 (0%) of 16 pulmonary carci noid tumors, in contrast to 24% and 33% of GI carcinoid tumors (P < .05) an d PETs (P < .05), respectively. TTF-1 expression was highly specific for pu lmonary carcinoid tumors. This peptide was present in 11 (69%) of 16 pulmon ary carcinoid tumors and in only 1 (2%) of 46 and 0 (0%) of 12 GI carcinoid tumors (P < .001) and PETs (P < .001), respectively. A CK7(+)/CK20(-)/TTF- 1(+) immunopanel result was moderately sensitive (sensitivity, 50%), and hi ghly specific (specificity, 100%), for a diagnosis of pulmonary carcinoid t umor. CK7, CK20, and TTF-1 did not differ significantly between carcinoid t umors located in different sites of the GI tract. However, a trend was obse rved toward a lower prevalence of CK20 positivity in gastric tumors (P = .0 6) than in GI carcinoid tumors from the small intestine, colon, or appendix . Expression of CK7 and CK20, and particularly TTF-1, may be useful in dist inguishing pulmonary from GI carcinoid tumors and PETs, especially when eva luated as a panel of markers. TTF-1 is highly specific for pulmonary carcin oid tumors. Hum PATHOL 32:1087-1093. Copyright (C) 2001 by W.B. Saunders Co mpany.