Clinical relevance of expression of the CIP/KIP cell-cycle inhibitors p21 and p27 in laryngeal cancer

Purpose: To investigate the prognostic relevance of p21 and p27 protein exp ression in laryngeal squamous eel carcinoma (LXC). 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 th ey had less than or equal to 10% of p21 and less than or equal to 50% of p2 7 immunoreactive neoplastic cells, Results: In 41 cases (31.1%), p21 was expressed in less than or equal to 10 % of neoplastic cells; in 91 cases (68.9%), it was expressed in more than 1 0% 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 neaplastic 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 clinica l stage. Expression of p21 and p27 was not correlated with p53 gene status, and tow p27 expression was more frequently detected in the cyclin D1-posit ive cases, with a border line level of statistical significance. At univari ate analysis, anatomic site, tumor extension, clinical stage, high cyclin D 1 expression, and low p27 expression were significantly associated with red uced disease-free and overall survival rates. At multivariate analysis, hig h cyclin D1 expression and low p27 expression were the only significant cov ariates, 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 evalua tion of p27 expression is a significant independent predictor of prognosis in laryngeal carcinoma. (C) 1999 by American Society of Clinical Oncology.