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
Hakan Bozcuk, Aziz Gumus, Gulay Ozbilim, Alpay Sarper, Ilknur Kucukosmanoglu, Irem H. Ozbudak, Mehmet Artac, Mustafa Ozdogan, Mustafa Samur, Abit Kaya, Burhan Savas
Med Sci Monit 2005; 11(6): HY11-20
Available online: 2005-06-01
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 affi liation.
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 affi liation 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 fi gures in the non-squamous cell carcinoma subgroup were nonmeasurable
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 affi liation with regard to
these biomarkers, and in relation to tumor histology, deserves further testing.
Keywords: Carcinoma, Non-Small-Cell Lung - chemistry, P-Glycoprotein - analysis, Adult, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung - surgery, Cluster Analysis, Combined Modality Therapy, Lung Neoplasms - surgery, Neoplasm Staging, P-Glycoprotein - analysis, Prognosis, Receptor, erbB-2 - analysis, Risk Factors, Smoking, Survival Analysis, Tumor Markers, Biological - analysis, Tumor Suppressor Protein p53 - analysis