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 distinguish adenocarcinomas from different sites. Thyroid transcription factor 1 (TTF-1) is a 38-kd protein, located primarily in the nucleus of type 2 pneumocytes and clara cells. TTF-1 has been shown to be present in a variety of lung and thyroid tumors and in pulmonary small-cell carcinomas. Carcinoid tumors from the lung and the gastrointestinal (GI) tract are histologically similar and thus are difficult to differentiate from each other based on histologic criteria. Pancreatic endocrine tumors (PET) have a similar histologic appearance to these other tumors. The purpose of this study was to determine the efficacy of differentiating these 3 groups of tumors by their expression of CK7, CK20, and TTF-1. Routinely processed paraffin-embedded tissue sections from 62 carcinoid tumors (lung, 16; gastrointestinal [GI] tract, 46) 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 cells positive), 2+ (11% to 25%), 3+ (26% to 50%), and 4+ (>50%). The data were compared between tumor types and between carcinoid tumors from the various locations in the GI tract (stomach, 8; small intestine, 19; large intestine, 17; appendix, 2). CK7 was expressed in 10 (63%) of 16 pulmonary carcinoid 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 similar to the findings in lung carcinoids and significantly higher than in GI carcinoids (P <.01). CK20 was expressed in 0 (0%) of 16 pulmonary carcinoid tumors, in contrast to 24% and 33% of GI carcinoid tumors (P <.05) and PETs (P <.05), respectively. TTF-1 expression was highly specific for pulmonary carcinoid tumors. This peptide was present in 11 (69%) of 16 pulmonary 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 highly specific (specificity, 100%), for a diagnosis of pulmonary carcinoid tumor. CK7, CK20, and TTF-1 did not differ significantly between carcinoid tumors located in different sites of the GI tract. However, a trend was observed toward a lower prevalence of CK20 positivity in gastric tumors (P =.06) 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 distinguishing pulmonary from GI carcinoid tumors and PETs, especially when evaluated as a panel of markers. TTF-1 is highly specific for pulmonary carcinoid tumors.
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Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002276:Carcinoid Tumor / Q000737:chemistry / Q000175:diagnosis / Q000378:metabolism* / Q000556:secondary; D003937:Diagnosis, Differential; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007340:Insulinoma / Q000737:chemistry / Q000378:metabolism* / Q000556:secondary; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000096:biosynthesis*; D053554:Keratin-20; D053552:Keratin-7; D007633:Keratins / Q000032:analysis / Q000096:biosynthesis*; D008175:Lung Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis / Q000096:biosynthesis*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; C507497:KRT7 protein, human; D053554:Keratin-20; D053552:Keratin-7; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D007633:Keratins