The expression of cyclins D₁ and E in predicting short-term survival in squamous cell carcinoma of the lung

Cyclins D₁ (cD₁) and E (cE) are G₁ phase cyclins believed to participate in the pathogenesis of malignancy. Overexpression of cD₁ has been reported to influence prognosis in squamous cell carcinomas (SCC) of the larynx, but was not significant in a limited study of non-small cell lung cancers (NSCLC). Altered expression of cE has been proposed as another potential prognostic marker in malignancy but its possible role in NSCLC has not been elucidated. In order to determine the prognostic value of cD₁ and cE in NSCLC, paraffinembedded sections of 467 NSCLC were immunostained with monoclonal antibody to cD₁ (1:500, PharMingen, San Diego, CA) and 400 NSCLC with MA to cE (1:2500, PharMingen) using an enhanced sensitivity avidin-biotin complex technique. The number of tumor cells with nuclear and/or cytoplasmic immunopositivity was graded on a scale of: 0 = less than 1%, 1 = 1 to 10%, 2 = 10 to 25%, 3 = 25 to 50%, 4 = 50 to 75%, 5 = more than 75%. Results were correlated with survival by Kaplan-Meier survival plot using Stat-View software (Abacus Concepts, Berkeley, CA). Overall, 426 NSCLC with cD₁ and 360 NSCLC with cE had adequate follow-up (median, 76 mo) for survival analysis. Both cyclins independently showed significance in prognosis of SCC but not other cell types. For cD₁, absence of immunostaining was associated with worse prognosis than any immunopositivity for all stages of SCC (P = .025). For cE, Stage I and II SCC with less than 50% immunopositivity had a worse prognosis (P = .029). Of 70 Stage I and II SCC immunostained for both monoclonal antibodies, 55% of patients with rumors that demonstrated both absence of cD₁ staining and cE immunopositivity in less than 50% of cells were dead at 5 years compared to 35% of patients with tumors that demonstrated positive staining with cD₁ and cE immunopositivity in more than 50% of cells. These results strongly suggest cD₁ and cE can independently predict prognosis in early stage SCC. Worse prognosis was associated with loss of expression, consistent with mechanisms other than overexpression of these cyclins in the progression of SCC.