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RESEARCH PRODUCT

Oncogene overexpression in non-small-cell lung cancer tissue: prevalence and clinicopathological significance.

subject

description

In contrast to small-cell lung cancer, few data are available on the role of oncogene overexpression in non-small-cell lung cancers (NSCLC). To determine the prevalence and extent of the transcriptional activation of cancer genes in NSCLC we investigated the level of mRNA of the three important cellular oncogenes — erbB2, Ki-ras, and c-myc — in 39 surgically or endoscopically obtained tumor samples and 24 samples of normal bronchopulmonary tissue taken from the same patients. Tissue RNA was prepared and the specific mRNA analyzed by the highly sensitive nuclease S1 protection assay. Oncogene mRNA in the tumors was quantified by comparison with the homogeneously weak signals in normal lung tissue preparations with densitometry. The presence of two- to four-fold excess RNA was defined as moderate and a greater than fourfold RNA amount as strong gene overexpression. In contrast to normal tissue the oncogene mRNA amount varied considerably among tumors, showing increases up to 64-fold in erbB2, 13-fold in Ki-ras, and 57-fold in c-myc. Moderate and strong (in brackets) mRNA overexpression occurred with 33% (33%) in erbB2, 36% (18%) in Ki-ras, and 18% (23%) in c-myc. Simultaneous overexpression of two genes was observed with 41 % and increased mRNA of all genes tested with 20% of the NSCLC samples. Augmented oncogene mRNA was observed most frequently in large-cell carcinoma. The c-myc overexpression was significantly more prevalent in large-cell cancer than in adenocarcinoma. Tumor differentiation was negatively correlated with c-myc mRNA amounts. This correlation was highly significant. The Ki-ras and c-myc over-expression was rare in the small subpopulation of seven nonsmokers, although high erbB2 mRNA levels were observed in all but one patient. Oncogene overexpression is a common phenomenon in clinical tissue specimens taken from NSCLC. This further emphasizes their role in the maintenance of the malignant phenotype in established tumors. The c-myc overexpression correlates with the loss of cell differentiation and may further correlate with the tumor stage.