Prognostic value of cell proliferation markers, tumour suppressor proteins and cell adhesion molecules in primary squamous cell carcinoma of the larynx and hypopharynx.

In an attempt to identify molecular prognostic markers, a series of laryngeal and hypopharyngeal carcinomas was examined for PCNA, Ki67, p27(Kip1), p53, E-cadherin and CD44 by immunohistochemistry and for DNA content by flow cytometry. No correlation was found between E-cadherin, CD44, p53 or DNA ploidy and the clinicopathological data. The fraction of cancer cells immunolabelled for p27(Kip1) correlated with tumour differentiation, but not with lymph node metastasis. In contrast, the PCNA, Ki67 and S-phase fractions of cancer cells were significantly higher in tumours with lymph node metastasis than in those without lymph node metastasis and were correlated with pathological T-stages and with tumour dedifferentiation. In univariate analysis, advanced pathological T-stage, lymph node metastasis and high fractions of cancer cells immunolabelled for PCNA or Ki67 inversely correlated with overall and disease-free survival. In multivariate analysis, lymph node metastasis was the only factor significantly associated with poor survival. The data suggest that immunohistochemical investigation of PCNA and Ki67 and flow cytometric analysis of S-phase fractions may be useful predictive markers of biological aggressiveness in laryngeal carcinomas.