Keratin proteins and carcinoembryonic antigen in lung carcinoma: An immunoperoxidase study of fifty-four cases, with ultrastructural correlations

Abstract

This study evaluates the use of immunoperoxidase stains for keratin and carcinoembryonic antigen (CEA) in the diagnosis of lung cancer. Immunohistochemical staining for these antigens was performed on paraffin sections from 54 lung neoplasms, and the results were correlated with the histologic, histochemical, and ultrastructural appearances of the tumors. Strong staining for keratin proteins was evident in all squamous cell carcinomas. This reaction was particularly helpful in identifying squamous differentiation in poorly differentiated areas and in cases in which tonofilaments appeared to be sparse or absent on electron microscopy. Weak focal staining for keratin was evident in only two cases of adenocarcinoma, and the difference in frequency of staining between squamous cell carcinomas and adenocarcinomas was statistically significant ( P =0.01). Carcinoembryonic antigen was variably present in all types of lung carcinoma, but staining for it was strongly positive in cases of adenocarcinoma. Positive staining for keratin with negative or focal weak staining for CEA was characteristic of mesotheliomas, which was helpful in differentiating them from adenocarcinomas. When evaluated by multiple means including immunohistochemical analysis, tumors with mixed differentiation were frequently identified and most large cell carcinomas showed evidence of glandular or squamous differentiation. Electron microscopic demonstration of neurosecretory granules was the best single diagnostic criterion for small cell anaplastic carcinomas ( P =0.01, as determined by stepwise logistic regression analysis). Also helpful in differentiating between small and large cell anaplastic carcinomas were a significantly smaller mean cell diameter in the former, as measured on electron micrographs ( P =0.05), and positive staining for keratin, which occurred significantly more often in large cell carcinomas ( P =0.03). These findings suggest that immunoperoxidase stains for keratin and CEA supplement routine histochemical and electron microscopic studies in the diagnosis of lung tumors, and may provide additional specific objective criteria for their classification.