Abstract
The identification of biomarkers to complement pathological stage for a more accurate prognosis and help clinicians decide on treatment is still an open problem for patients with lung cancer. Expression of P53 protein was detected by an immunohistochemical approach using the monoclonal antibody PAb1801 on paraffin-embedded sections of tumours obtained surgically from 102 stage II - IIIa patients with non-small-cell lung cancer (52 squamous cell carcinomas, 50 adenocarcinomas). [3H]Thymidine labelling index, an indicator of the S-phase cell fraction, was evaluated on histological sections of [3H]thymidine-labelled tumour samples. DNA ploidy was defined by flow cytometric analysis on frozen tumour tissue. The biomarkers, histology and pathological stage were analysed in relation to relapse-free survival in univariate and multivariate analyses. Stage and interaction between [3H]thymidine labelling index and histology provided significant prognostic information for the overall series. [3H]thymidine labelling index was an independent prognostic indicator of 3 year relapse-free survival in patients with adenocarcinoma. The results indicate the importance of cell proliferation to complement prognostic information provided by pathological stage in patients with stage II-IIIa adenocarcinomas.
Highlights
DNA ploidy was defined by flow cytometric analysis on frozen tumour tissue
The biomarkers, histology and pathological stage were analysed in relation to relapse-free survival in univariate and multivariate analyses
The results indicate the importance of cell proliferation to complement prognostic information provided by pathological stage in patients with stage IILIIa adenocarcinomas
Summary
From February 1988 to June 1992, 126 consecutive patients with operable stage II or IlIa NSCLC underwent surgery at the Istituto Nazionale Tumori of Milan, Italy. After surgery, pathological material from different areas of the tumour was (1) processed for conventional histological procedures, after previous incubation with [3H]thymidine, and (2) frozen in liquid nitrogen and stored at - 80°C for DNA content determination. Tumour fragments were incubated for 1 h with a DNA precursor, [3Hithymidine, and fixed in formalin These steps of the procedure were carried out using a commercial kit (Ribbon, Milan, Italy). The prognostic role of the variables was evaluated by a Cox regression model in univariate and in multivariate analyses. Hazard ratios and their 95% confidence limits (CL) were determined by using as a reference the putative best prognostic category.
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