Heterogeneity of expression of cytokeratin subtypes in squamous cell carcinoma of the lung: with special reference to CK14 overexpression in cancer of high-proliferative and lymphogenous metastatic potential.

In surgically resected specimens of squamous cell carcinoma (SCC) of the lung from 45 patients, we immunohistochemically examined the expression of 13 subtypes of cytokeratin (CK), the intermediate filament in cytoplasm of epithelial cells. To investigate heterogeneity of CK, its expression was compared among tumor cell nests with or without keratinization and stratification. Furthermore, the relationship between CK expression and Ki-67 labeling index or p53 expression was investigated. The tumor cell nests with keratinization showed the expression of CK1 and CK10 as a central pattern and the expression of CK14 as a peripheral pattern. The nests with stratification showed CK14 expression as a peripheral pattern, whereas those without stratification showed the expression as a diffuse pattern. The tumor cell nests showing stromal invasion with fibrosis in the marginal zone were diffusely positive for CK14. Ki-67 antigen labeling index was significantly higher in the nests where CK14 expression was diffuse or peripheral than in the nests where the expression was focal or negative. In lymph node metastases, the tumor cells often showed CK14 expression, like trabecular nests in the primary carcinoma. These results suggest that CK14 is a parameter of proliferative activity and metastatic potential of SCC of the lung.