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Clinical Relevance of Expression of the CIP/KIP Cell-Cycle Inhibitors p21 and p27 in Laryngeal Cancer

From the II Servizio di Anatomia Patologica, Clinica Otorinolaringoiatrica I, Laboratorio Epidemiologico, Laboratorio di Ematologia Sperimentale e Genetica Molecolare, Servizio di Ematologia, Istituto di Scienze Mediche, Università di Milano, Ospedale Maggiore di Milano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.

Address reprint requests to Antonino Neri, MD, Servizio Ematologia, Centro "G. Marcora," Ospedale Maggiore, IRCCS, Via F. Sforza 35, 20122, Milano, Italy; email sap2{at}imiucca.csi.unimi.it

PURPOSE: To investigate the prognostic relevance of p21 and p27 protein expression in laryngeal squamous cell carcinoma (LSCC).

PATIENTS AND METHODS: We have analyzed by immunohistochemistry p21 and p27 expression in a series of 132 patients who underwent surgical resection of their LSCC and who had previously been investigated for p53 gene mutations and cyclin D1 expression. The tumors were considered low expressors when they had 10% of p21 and 50% of p27 immunoreactive neoplastic cells.

RESULTS: In 41 cases (31.1%), p21 was expressed in 10% of neoplastic cells; in 91 cases (68.9%), it was expressed in more than 10% of neoplastic cells. In 11 cases (8.3%), p27 was expressed in less than 5% of neoplastic cells; in 39 cases (29.6%), it was expressed in 5% to 50% of neoplastic cells; and in 82 cases (62.1%), it was expressed in more than 50% of the neoplastic cells. Low levels of p21 expression were associated with poor histologic differentiation and lymph node metastases. Low levels of p27 expression were associated with tumor extension and advanced clinical stage. Expression of p21 and p27 was not correlated with p53 gene status, and low p27 expression was more frequently detected in the cyclin D1–positive cases, with a borderline level of statistical significance. At univariate analysis, anatomic site, tumor extension, clinical stage, high cyclin D1 expression, and low p27 expression were significantly associated with reduced disease-free and overall survival rates. At multivariate analysis, high cyclin D1 expression and low p27 expression were the only significant covariates. The patients with a cyclin D1⁺/p27^- phenotype had the poorest disease-free and overall survival rates.

CONCLUSION: Our study provides evidence that the immunohistochemical evaluation of p27 expression is a significant independent predictor of prognosis in laryngeal carcinoma.

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