Negative Expression Of Fhit In Lung Cancer And Its Correlation With Smoking

Lung cancer is one of the most common cause of cancer in the world. Over the past 40 years, although there were a certain improvements on surgery, chemotherapy, radiotherapy and immunotherapy, its overall survival rate was low.Deletions of short arm of chromosome 3 are considered critical events hi the pathogenesis of lung cancer. Fragile Histidine Triad gene ( FHIT ), locating at 3pl4. 2, is a candidate tumor suppressor gene. It's controversial about the role of FHIT in human cancer (including lung cancer).The aim of this study was to investigate FHIT gene protein (Fhit ) expression in lung cancer, and to determine the association between Fhit expression and clinicopathological features.MATERIALS AND METHODSA Total of fifty-six tumor blocks and the matched normal bronchial tissues in a different segment or lobe or at a most distant site (>3cm)of the tumor, and 21 non-malignant pulmonary diseases tissues (including 5 pulmonary tuberculosis, 2 bronchiectasis, 11 organizational pneumonias, and 3 fungous granulomas) were obtained from surgically resected blocks at the First Affiliated Hospital, Medical College , Zhejiang University, or the second People's Hospital of Hangzhou City from September 2000 to January 2001. Of the 56 lung cancers, there were 33 squamous cell carcinomas,21 adenocarcinomas (including 6 bronchialoalveolar carcinomas) and 2 large cell carcinomas. A detailed smoking history was available and there were 16 never/non-smokers and 40 smokers or former smokers with mean pack-years of 43(range 5-57.5).Fhit expression was detected with immunohistochemistry SP method. Histostain TM-plus kits was purchased from Zhongshan Bio-technique company, Beijing. Poly ctonal Rabbit Anti-Fhh was purchased from ZYMED Laboratories, INS. So. San Francisco, CA.Attest was used to examined the association of two categorical variables.Statistical analysis was performed using the SPSS statistical package.RESULTS and DISCUSSIONAll the fifty-six matched normal bronchial tissues and 21 non-malignant lung diseases tissues showed positive Fhit expression. However, 33 of 56 (58.9%) lung tumor showed marked reduction or absence of cytoplasmic staining. The remaining 23 lung cancers was characterized cytoplasmic stain of neoplastic cellIn addition, there was a significant correlation between Fhit expression and cancer histology.24 of 33 (72.7%) hing cancer with squamous differentiation were Fhit-negative. In contrast, only 9 of 23(39.1%) with non-squamous differentiation, including 8 of 21(38.1%) adenocarcinomas and 1 of 2(50%) large call carcinomas, were Fhit-negative (72.7% vs39.1%, P=0.012).When FHft expression was compared with smoking habits, the frequency of Fhit-negative tumors in smokers(27/40,67.5%) was significantly higher than it was in tumors from non-smokers(6/16,This study confirms that loss of Fhit is frequent in lung cancer, especially in SqCCs and that it is strongly related with smoking. These results suggest that the detection of Fhit expression would provide a useful marker for diagnosis of lung cancer, and that FHIT could play a role in the smoking-related lung tumorigenesis.CONCLUSIONS1 % Abnormality of FHIT gene is a frequent event in lung cancer. 2> FHIT is a candidate molecular target of carcinogens containedin tobacco smoke.