Comparison of the immunophenotypes of signet-ring cell carcinoma, solid adenocarcinoma with mucin production, and mucinous bronchioloalveolar carcinoma of the lung characterized by the presence of cytoplasmic mucin



The latest World Health Organization (WHO) classification divides adenocarcinoma mainly into adenocarcinoma mixed subtypes, acinar adenocarcinoma, papillary adenocarcinoma, bronchioloalveolar carcinoma, and solid adenocarcinoma with mucin production, and it mentions several variants, including fetal adenocarcinoma, mucinous (“colloid”) adenocarcinoma, mucinous cystadenocarcinoma, signet-ring adenocarcinoma, and clear cell adenocarcinoma. In general, the mucin-producing adenocarcinoma of the lung comprises signet-ring cell carcinoma (SRCC), solid adenocarcinoma with mucin production (SA), and mucinous bronchioloalveolar carcinoma (m-BAC), mucinous (“colloid”) adenocarcinomas and/or mucinous cystadenocarcinoma, and mucoepidermoid carcinoma. As SRCC, SA, and m-BAC exhibit distinct clinical features, it is important to identify differences in their immunohistochemical characteristics to better understand their histogenesis. In this study we analysed SRCC, SA, m-BAC, normal lung, and foregut-related secretory tissue for immunohistochemical differences using tissue microarrays. SRCC and SA showed high expression of MUC1 (97.4% and 100%, respectively), cytokeratin (CK) 7 (both 100%), and thyroid transcription factor-1 (TTF-1) (81.1% and 100%, respectively). They also showed low expression of MUC5AC (25.5% and 21.1%, respectively) and MUC6 (18.3% and 10.5%, respectively), whereas m-BAC showed high expression of MUC5AC (97.5%), MUC6 (75.0%), and CK7 (94.7%), but low expression of MUC1 (57.5%), and TTF-1 (27.5%). Hierarchical clustering showed that the immunophenotypes of SRCC and SA belong to the same category as alveolar lining cells, whereas m-BAC clustered onto another branch with gastric foveolar cells and bronchial goblet cells. These immunohistochemical findings support the results of our previous clinicopathological analysis of SRCC of the lung showing that SRCC occurs anatomically in the peripheral portion of the lung rather than in the bronchial gland-bearing portion. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.