Expression of cyclin D1, Ki-67 and PCNA in nonsmall cell lung cancer: prognostic significance and comparison with p53 and bcl-2

Uncontrolled cell proliferation is the hallmark of malignant tumours. Thus, the proliferative potential of tumour cells is an important prognostic fac tor. However, evaluation of the prognostic significance of the expression o f proteins involved in regulation of cell proliferation remains controversi al. In the present study, expression of Ki-67, PCNA and cyclin D1 was estim ated in a group of 89 surgically resected non-small cell lung carcinomas us ing immunohistochemistry, The results were compared with expression of bcl- 2 and p53 and with clinicopathological parameters including patients' survi val. Ki-67 and PCNA were found to be moderately and highly expressed in 39% and 44% of the tumours, respectively. There was a strong correlation betwe en Ki-67 and PCNA expression. Forty five of 88 tumours (51%) showed overexp ression of cyclin D1. Surprisingly, cyclin D1 was mainly localized in the c ytoplasm and only a small group of tumours (9/88, 10%) showed nuclear stain ing as well. Bcl-2 and p53 expression was observed in 69% and 30% of the tu mours, respectively, All these markers were found to be independent of clin icopathological parameters, except for Ki-67 and bcl-2 expression, which wa s associated with squamous cell carcinomas, It is concluded that none of th e markers that were studied can be used as an independent prognostic factor , whereas the following combinations of markers may have favourable prognos tic value: p53 positivity and low Ki-67 expression, p53 positivity and lack of cyclin D1 expression, bcl-2 positivity and low Ki-67 expression, and la ck of cyclin D1 expression and low Ki-67 expression.