Claudin-1 and claudin-5 expression patterns differentiate lung squamous cell carcinomas from adenocarcinomas

We investigated the expression of tight junction proteins in human lung squamous cell carcinomas and adenocarcinomas by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction ( RT-PCR). We found a statistically significant correlation between diagnosis and positivity of tumors with either claudin ( CLDN)- 1 or CLDN- 5. Squamous cell carcinomas and basal cells of bronchial epithelium were positive for CLDN- 1 and negative for CLDN- 5, whereas adenocarcinomas, normal cylindrical cells and pneumocytes were positive for CLDN- 5 and negative for CLDN- 1, suggesting different pathways in tumor development and progression. CLDN- 4 and ZO-1 staining were detected in both types of tumors, whereas cingulin ( CGN) was not detected in squamous cell carcinomas. Quantitative RT-PCR was used to evaluate changes in transcript levels for a large panel of tight junction proteins. In squamous cell carcinomas, we observed statistically significant decreases in the mRNA levels of JAM- 1, occludin, CLDN- 3, CLDN- 4, CLDN- 7, CGN, ZO-2 and ZO-3, and an increase in CLDN- 1 mRNA. In adenocarcinomas, when transcript levels were compared with bronchial cells, we observed statistically significant decreases in the mRNA levels of CLDN- 1, CLDN- 3, CLDN- 4, CLDN- 7, ZO-2 and ZO-3. These results indicate that characterization of tight junction protein expression in human lung tumors can be an additional diagnostic tool and provide new insights on their histogenesis.