Protein Expression Profiles of Non-small Cell Lung Carcinomas: Correlation with Histological Subtype

Of the four major subtypes of lung cancer, three subtypes, namely squamous cell lung carcinomas, adenocarcinomas and large cell carcinomas are usually combined within the larger group of non-small cell lung carcinomas (NSCLC). However, the heterogeneity that exists within any given tumor has also been clearly demonstrated. In order to study whether or not the protein expression profile is different in the histological subtypes of NSCLC, the expression of several parameters including proto-oncogene and suppressor gene products, proliferative, apoptotic, angiogenic and resistance factors was evaluated immunohistochemically in 139 NSCLC (45 adenocarcinomas and 94 squamous cell lung carcinomas). In both histological subtypes the percentage of positively-stained parameters was determined. The expression of the proteins ERBB2, JUN, RAS and tissue factor was significantly higher in adenocarcinomas compared to squamous cell lung carcinomas. In contrast, all resistance proteins analyzed were more frequently expressed in squamous cell lung carcinomas in comparison to adenocarcinomas, though only GST-pi reached statistical significance. Apoptotic factors and angiogenic factors were higher in adenocarcinomas, but these differences did not reach statistical significance. In conclusion, the protein expression profiles of adenocarcinomas and squamous cell carcinomas differ from each other. Squamous cell lung carcinomas in comparison to adenocarcinomas are characterized by a down-regulation of some oncogenes and an up-regulation of several resistance factors. These findings could explain the different biological behaviour and treatment response of these tumours.