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Prognostic significance of p53 and bcl-2 abnormalities in operable non-small cell lung cancer

Depts of ¹ Thoracic Surgery, ² Histology, ⁴ Clinical Molecular Biology, Medical Academy of Bialystok, ³ Center for Statistics, Limburgs Universitair Centrum, Diepenbeek, Belgium and ⁵ Biostatistical Unit, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

CORRESPONDENCE: J Niklinski, Dept of Thoracic Surgery, Medical Academy of Bialystok, 24A M Sklodowska-Curie St, 15-276, Bialystok, Poland. Fax: 48 857423537

Keywords: bcl-2, lung cancer, p-53, prognosis

Received: February 14, 2000
Accepted October 26, 2000

This study was supported by the Polish Scientific Programme (KBN No. 4 P05C 079 15 and KBN No. 4PO5B 048 19).

The association of p53 abnormalities and bcl-2 protein expression with clinical data and prognosis in 102 patients with resected non-small cell lung cancer (NSCLC) was investigated.

Deoxyribonucleic acid analysis of exons 5–8 of the p53 gene showed mutations (p53-M) in 47% of resected NSCLC, serum p53 antibodies (p53-Abs) were detected in 25%, p53 protein overexpression (p53-PE) in 54% and bcl-2 protein overexpression (bcl-2-PE) in 48%. A statistically significant association was found between p53-PE, serum p53-Abs and the presence of a p53 gene alteration. No significant associations were found between results of the p53-M, p53-Abs, bcl-2-PE tests and clinicopathological parameters. In the case of the p53-PE test there were significantly fewer positive results for adenocarcinoma than for squamous cell carcinoma and large cell carcinoma.

Survival analysis showed that both p53 abnormalities and negative staining for bcl-2, when analysed separately, were associated with poor overall survival. In a multivariate analysis, only the positive result of the p53-M test remained an independent, statistically significant, unfavourable prognostic factor for survival. When the p53 mutation test was removed from the model, positive results of the p53-PE test and the p53-Abs test became statistically significant, unfavourable prognostic factors.

To conclude, among p53 and bcl-2 abnormalities, only p53 gene mutations seem to have a strong and independent effect on prognosis. When deoxyribonucleic acid sequence information is not available, p53 protein expression and the presence of p53 antibodies in serum may be used to obtain important prognostic information.

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