Non-small cell lung cancer: c-erbB-2 overexpression correlates with low angiogenesis and poor prognosis.
Giatromanolaki A., Koukourakis MI., O'Byrne K., Kaklamanis L., Dicoglou C., Trichia E., Whitehouse R., Harris AL., Gatter KC.
Tumour angiogenesis is an important prognostic factor in non-small cell lung cancer. Recently, EGFR and c-erbB-2 protein was found to regulate cell adhesion and the invasive growth of cancer through its association with the cadherin-catenin complex. The role of c-erbB-2 protein in cell migration has been also reported. In this study we investigate the combined role of tumoral neoangiogenesis and c-erbB-2/EGFR expression in the metastatic behaviour and prognosis of operable non-small cell lung cancer. 107 tumour samples from patients suffering from operable non small cell lung cancer were examined. EGFR and c-erbB-2 were not correlated with each other. C-erbB-2 expression was associated with low angiogenesis, approaching statistical significance in adenocarcinomas (p = 0.08). The absence of expression of both c-erbB-2 and EGFR oncogenes in tumours with high angiogenesis, was most frequently observed in node negative cases (p = 0.04). C-erbB-2 overexpression defined a subgroup of node negative patients with low angiogenesis and prognosis similar to patients with tumours bearing high angiogenesis. These findings support the hypothesis that expression of the erb genes is a mechanism activated in non-small cell lung cancer to enable cancer cell migration. This pathway seems to be activated mainly in tumours with poor vasculature presumably lading to an unfavourable intratumoral nutritional and oxygen ambience.