Low p27 expression correlates with poor prognosis for patients with oral tongue squamous cell carcinoma

BACKGROUND. p27, a cyclin-dependent kinase inhibitor, regulates progression from G1 to S phase. There have been a few clinical reports of low p27 expr ession associated with poor survival among patients with cancer; however, t here have been no reports of such an association in cases of head and neck cancer. The authors investigated whether p27 expression in patients with or al tongue squamous cell carcinoma was associated with their prognosis. METHODS. Ninety-four patients with oral tongue squamous cell carcinoma were analyzed. The authors performed p27 immunohistochemistry on all patients a nd Western blot analysis on 19 available patients. Cox proportional hazards regression analysis that included gender, history of smoking and alcohol u sage, presence of multiple primary cancers, stage, histologic grade, and p2 7 status was used to identify the multivariate predictive value of prognost ic factors. RESULTS. Twenty-six patients had high p27 expression (greater than or equal to 50% tumor cell nuclei positive), and 68 patients had low p27 expression (<50%) by immunohistochemistry. In those with low p27 expression, N(+) and advanced T (T3 or T4) were significantly higher than in those with high p2 7 expression (P = 0.02 and 0.04). The 5-year survival rate in the low p27 g roup was 44%, whereas that in the high p27 group tvas 68%, indicating a sig nificant difference (P = 0.04). p27 expression was inferred from Western bl ot analysis, and an arbitrary quantity (<1, 1-5, or greater than or equal t o 5) from the ratio of tumor to normal tissue density was used to character ize, resulting in 8 (42%), 3 (16%), and 8 (42%) patients in the low (<1-fol d), intermediate (1-5-fold), and high (greater than or equal to 5-fold) gro ups, respectively. Results of immunohistochemical analysis for p27 were sig nificantly correlated with those of Western blot analysis (P = 0.02). Multi variate analysis revealed that low intensity of p27 expression and advanced stage (Stage III or IV) were predictors of reduced survival (P = 0.02 and 0.001). CONCLUSIONS. Low p27 expression was associated with increasing lymph node m etastasis and stage of tumor and resulted in a poor prognosis for patients with oral tongue squamous cell carcinoma. p27 is apparently a significant p redictor of survival. Cancer 1999;85:1011-7. (C) 1999 American Cancer Socie ty.