Background: The lung carcinoma is a major cause of cancer-related death, but molecular aspects of its genesis and progression remain unclear. The present study aimed to clarify the roles of FHIT and PTEN expression.
Materials and methods: Expression of FHIT and PTEN was examined using tissue microarrays (TMAs) of lung carcinoma (n = 155) and normal lung samples (n =40) by immunohistochemistry and compared with clinicopathological parameters of tumors, including expression of CPP32 and Ki-67, as well as survival time of patients.
Results: PTEN was positively expressed in the nuclei of stratified squamous and alveolar epithelial cells, and FHIT in the cytoplasm of stratified squamous and type II alveolar epithelial cells. Both were more frequently expressed in normal lung tissues than lung carcinomas (p<0.05). Immunohistochemically, PTEN expression gradually decreased from small cell carcinomas (SCCs), through large cell carcinomas (LCCs) and adenocarcinomas (ADs) to squamous (SQ) cell carcinomas (p <0.05), whereas FHIT was more highly expressed in ADs and LCCs, compared with SQs and SCCs (p <0.05). PTEN expression was negatively linked to lymphatic and venous invasion of tumors (p<0.05), but positively to CPP32 expression (p<O0.05). FHIT expression was higher in females than males (p<0.05), and negatively related to Ki-67 expression (p<0.05). Kaplan-Merier analysis indicated that expression of PTEN, but not FHIT, was positively correlated with a high cumulative survival rate for patients with lung carcinomas even after stratified analysis of the histological classification (p<0.05).
Conclusion: PTEN and FHIT may contribute to regulation of the balance between apoptosis and proliferation in physiological events in normal lung and during development of lung carcinoma. Down-regulated PTEN appears closely linked to frequent lymphoangiogenic invasion and low FHIT expression, and could provide a molecular basis for differences in genetic sensitivity between men and women to lung carcinogens. PTEN could be a good prognostic factor for lung carcinomas, regardless of the histological types.