The value of cytokeratins 20 and 7 in discriminating metastatic adenocarcinomas from pleural mesotheliomas.
BACKGROUND
Immunohistochemistry is a useful method in the differential diagnosis between pleural mesotheliomas and metastatic adenocarcinomas to the pleura. Cytokeratin (CK) 5-6 is one of the most specific mesothelioma-associated antibodies. Cytokeratin 20 and CK7 have been used successfully in studies determining primary location of adenocarcinomas from metastases. In the current study, the value of these CKs in differential diagnosis of malignant pleural lesions was examined.


METHODS
Ninety-three autopsy-verified cases (14 mesotheliomas and 79 adenocarcinomas including 42 primary lung tumors and 37 adenocarcinomas metastatic to the pleura) were stained on CK20, CK7, and CK5-6 with commercially available primary antibodies. The staining was conducted in an automated immunohistochemical system. The results were analyzed statistically at different positivity thresholds: 10% and 0%.


RESULTS
None of the mesotheliomas stained positively for CK20 at the 10% positivity level, but 3 cases showed focal positivity in < 10% of the tumor cells. Eighty-six percent (12 of 14) of these tumors were CK7+ and 64% (9 of 14) were CK5-6+. None of the mesotheliomas expressed the CK20+/7- pattern. Lung adenocarcinomas, both primary and metastatic, and breast carcinomas were very similar to mesotheliomas with regard to expression of CK20 and CK7 but differed significantly with regard to expression of CK5-6. Conversely, gastrointestinal adenocarcinomas and pancreaticobiliary tumors expressed CK20 positivity in a high proportion, 86% (13 of 15) and 77% (7 of 9), respectively. The gastrointestinal tumors stained positively for CK7 in only 20% (3 of 15) of cases and differed significantly from the other adenocarcinomas in this aspect. The CK20+/7- pattern was typical for gastrointestinal tumors.


CONCLUSIONS
Adding CK20 and CK7 to the panel of antibodies in the differential diagnosis of pleural mesothelioma versus metastatic adenocarcinomas is useful because diffuse CK20 positivity seems to be an indicator of metastasis. Furthermore, CK7 negativity most often is associated with metastases, and the CK20+/7- pattern, typical of colorectal adenocarcinomas, is absent in pleural mesotheliomas.
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Department of Pathology and Clinical Cytology, Central Hospital, Falun, Sweden. tibor.tot@ltdalarna.se
D000230:Adenocarcinoma / Q000175:diagnosis / Q000556:secondary*; D001344:Autopsy; D014408:Biomarkers, Tumor / Q000032:analysis*; D003937:Diagnosis, Differential; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000032:analysis*; D053554:Keratin-20; D053552:Keratin-7; D007633:Keratins / Q000032:analysis*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000556:secondary*; D008654:Mesothelioma / Q000175:diagnosis* / Q000473:pathology; D009362:Neoplasm Metastasis; D010997:Pleural Neoplasms / Q000175:diagnosis / Q000556:secondary*; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; C507497:KRT7 protein, human; D053554:Keratin-20; D053552:Keratin-7; D007633:Keratins