Cluster analysis of p-glycoprotein, c-erb-B2 and P53 in relation to tumor histology strongly indicates prognosis in patients with operable non-small cell lung cancer.

BACKGROUND: Various biomarkers have prognostic value in non-small cell lung cancer (NSCLC). We aimed to identify the roles of P53, c-erb- B2 and p-glycoprotein (pgp) as prognostic factors, independently or in conjunction with each other, in operable NSCLC.

MATERIAL/METHODS: Seventy operable NSCLC cases were retrospectively evaluated for P53, c-erb-B2 and pgp expression patterns by immunohistochemistry. An unsupervised hierarchical cluster analysis of the 3 biomarkers was conducted. Univariate and multivariate survival analyses were made in relation to cluster affiliation.

RESULTS: Cluster analysis yielded two distinct subgroups; group A of high biomarker expressors (n=26, 37%), and group B (n=44, 63%) of low expressors. Cluster affiliation with regard to tumor histology (interaction term) was independently associated with Recurrence- free survival (RFS) and Overall survival (OAS) with a Hazard Ratio (HR) of 5.88, P=0.003, and HR=4.68, P=0.012, respectively. The median OAS times for cluster A and B in the squamous cell carcinoma subgroup were 328 and 596 days, whereas the corresponding figures in the non-squamous cell carcinoma subgroup were non-measurable and 298 days.

CONCLUSIONS: In operable NSCLC there may be different relationships of P53, c-erb-B2 and pgp with patient outcome for different tumor histologies. The prognostic utility of cluster affiliation with regard to these biomarkers, and in relation to tumor histology, deserves further testing.