Prognostic significance of p27 and ki-67 expression in mucoepidermoid carcinoma of the intraoral minor salivary gland

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Prognostic Significance of p27 and Ki-67 Expression in Mucoepidermoid Carcinoma of the Intraoral Minor Salivary Gland
Mitsukuni Okabe, D.M.D., Hiroshi Inagaki, M.D., Takayuki Murase, M.D., Masahisa Inoue, D.M.D., Noriyuki Nagai, D.M.D., Tadaaki Eimoto, M.D. Department of Pathology (MO, HI, TM, TE), Nagoya City University Medical School, Nagoya, Japan; and Department of Oral Pathology (MI, NN),Okayama University Dental School, Okayama, Japan

p27 and Ki-67, a universal cyclin-dependent kinase inhibitor and a proliferative cell marker, respectively, have been useful in predicting clinical aggressiveness in various human tumors. We studied clinicopathologic significance of these molecules in mucoepidermoid carcinoma of the intraoral minor salivary gland. Expression of p27 and Ki-67 wasassessed immunohistochemically in primary mucoepidermoid carcinomas from 31 patients without distant metastasis at surgery. Correlation each of p27 and Ki-67 expression was analyzed with various clinicopathologic parameters including age, sex, primary tumor site, tumor size, nodal metastasis, clinical stage, and histologic grade. The latter was evaluated using a point-scoring scheme of Auclair etal. that consists of five histologic factors (intracystic component, neural invasion, necrosis, mitosis, and anaplasia). p27 expression was correlated inversely with histologic grade (P .007), but with none of other factors. When the correlation of p27 expression was further examined with each of the histologic factors, it was correlated significantly with intracystic component, but not with neuralinvasion, necrosis, mitosis, or anaplasia. Ki-67 expression was correlated significantly with histologic grade only in the clinicopathologic factors (P < .0001), and in the histologic factors, with necrosis, mitosis, and anaplasia. Multivariate prognostic analyses were performed to identify independent risk factors for both disease-free and overall survivals. Large tumor size (P .031, relativerisk 5.5) and low p27 expression (P .012, relative risk 5.2) were risk factors for worse disease-free survival. Low p27 ex-

pression (P .015, relative risk 15.2) was selected as a risk factor for worse overall survival. Other factors including age, sex, tumor site, nodal status, clinical stage, histologic grade, and Ki-67 did not emerge as independent risk factors in either prognostic analysis.These data suggest that p27 may be useful in estimating prognosis of the patients who have mucoepidermoid carcinoma of the intraoral minor salivary gland. KEY WORDS: p27, Ki-67, Histologic grade, Intraoral mucoepidermoid carcinoma, Prognosis, Survival analysis. Mod Pathol 2001;14(10):1008 –1014 Mucoepidermoid carcinoma (MECA) is the most common malignant tumor of the minor salivary gland in theoral cavity (1). However, most of the previous clinicopathologic studies for MECA include cases of both major and minor salivary glands. The number of such studies restricted to MECA of the intraoral minor salivary gland is limited (2– 6), and prognostic factors for this tumor have been poorly clarified. Recently, some cell cycle-associated molecules have been useful in predicting survival of thepatients with various malignant tumors. p27 is a member of the universal cyclin-dependent kinase inhibitor family (7). p27 blocks the cell cycle at the G1/S phase checkpoint and is highly expressed in cells arrested at the G0 and G1 phases. Enhanced p27 expression is induced by cell– cell contact and specific growth factors, such as transforming growth factor- (8, 9) and cyclic AMP (10). Prognosticvalue of p27 expression has been reported in various human tumors (11). The low p27 expression was associated with an unfavorable prognosis for squamous cell carcinoma of the tongue (12). However, the significance of p27 has not been studied in MECA of either major or minor salivary gland origin.

Copyright © 2001 by The United States and Canadian Academy of Pathology, Inc. VOL. 14, NO. 10, P....
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