The Correlation Research Between The Expression Of FHIT And The P21～(WAF/CIP),PCNA In Non-Small-Cell Lung Cancer

[Background and Objective]Lung cancer is one of the diseases that threatened the humanity health seriously. According to the epidemical statistical date ,lung cancer was the number one killer in urban population and the number three killer in rural population in 1990s because of the discovered patients always in middle or late stage of theirs disease. At present, the therapeutical measures were still operation , radiotherapy , chemotherapy and the side effect were still high. The five-year survival rate was only 13%. The research demonstrated that the happening of lung cancer were the activation of carcinoma gene and the inactivation of suppressor gene which leads to the out of control of the cell growth. Wherease , it is more important to clarity the molecular basis and search for a new idea about lung cancer at gene level. FHIT gene was regarded as the potential clinical applicable target gene that has the effect in diagnosis and treatment because of its high abnormality frequency in the early stage of multi-carcinoma or even in the stage of precancerous lesion such as atypical apoptosis . It is not clear about action mechanism and its action access and it is remained to explore the relationship between FHIT gene as well as its expression protein and the other important related carcinoma gene ( for example p21, pl6,CDK,PCNA ) which in charge ofproliferation , differentiation ,apoptosis and so on . The main purpose of the experimentation is to research the expression of FHIT , P21WAF/CIP, PCNA and their correlation in lung benign lesion and lung cancer tissue, seek the effect of FHIT in non-small cell lung cancer and provide the theoretical basis in genetic diagnosis and therapy of lung cancer.[Materials and Methods]80 cases diagnosed by surgical resection and pathology were collected as experimentation group , of which male 50 ,female 30, age from 20 to 79, average 59.25 + 6.78; Squamous cancer 42, adenocarcinoma 38. In squamous cancer cases, well-differentiated 16, moderate 14, poorly-differentiated 12, and 25 cases with lymph node metastasis, 17 with no lymph node metastasis. In adenocarcinoma, well-differentiated 12, moderate 12, poorly-differentiated 14., and 26 with lymph node metastasis , 12 with no lymph node metastasis. Of all the cases there were 43 with smoking history of which squamous cancer cases 28 , adenocarcinoma cases 15, and 37 with no smoking history ,of which squamous cancer cases 14 , adenocarcinoma 23. According to the lung cancer stage criteria of UICC in 1997, there were 52 cases in stage I-II ,28 cases in III-IV . And all the cases didn't receive chemothrrapy or radiotherapy. 40 cases of benign lung lesions were collected as control group. All the tissues were from the first affiliated hospital zhengzhou university and He nan chest hospital and were confirmed by pathology . The cases were fixed in 10% neutral formalin and embedded in paraffin. SP immunohistochemical method was performed to detect the expressions of FHIT, P21WAF/cip and PCNA The data were analyzed by software SPSS 10.0, Chi-square Test were used to compare the difference of FHIT, p21~WAF/cip and PCNA expression among groups. The relationship between them used Spearmans method. a=0.05 was considered as level of tests. P< 0.05 was the standard of obvious difference.[Results]l.The positive rate(57.5%) of FHIT in lung cancers was significantly lower (p<0.01) than that of FHIT in benign tissues (90.0%). The positive rate ofFHIT(38.1%) in squamous cancer was significantly lower (/?<0.01) than that of FHIT in adenocarcinoma (78.9%). The positive expression rate of FINT has relationship with the squamous cancer differentation level and lymph node metastasis (p<0.05). The positive expression rate of FINT in non-smoking group is higher than that in smoking group(p<0.05). The positive expression rate of FINT in stageI~II cases is higher than that in stage III-IV cases group (p<0.05). And has no relationship with age ,gender, and adenocarcinoma lymph node metastasis (p>0.05).2.The positive rate of P21WAF/cip in NSCLC (76.3%) was significantly higher O<0.01) than that in benign tissues (25.0%).The positive rate of P21WAF/cip in the squamous cancer and adenocarcinoma were 71.4% , 78.9% , and has on statistical significance(p<0.05). There was significant relationship between positive p21waf/c|p expression and tumor differentation, and no significant relationship was found between positive P21WAF/Cip exprssion and age ,gender, lymph node metastasis of adenocarcinoma, P-TNM staging (p>0.05).3.The positive rate of PCNA in NSCLC (60.0%) was significantly higher (p<0.05) than that in benign tissues (10.0%). In squamous cancer and adenocarcinoma, the positive rates of PCNA expression were 47.6% and 73.7% respectively, the difference between them was significant(p<0.05). There was significant relationship between positive PCNA exprssion and lymph node metastasis as well as P-TNM staging(p<0.05). No significant relationship was found between positive PCNA exprssion and age, gender, ,tumor differation ,smoking history. (p>0.05)4. In NSCLC the expression rate of FINT has negative correlation with PCNA protein and positive correlation with p21WAF/cip protein. There is no correlation between the expression of p21WAF/cip and that of PCNA protein (p>0.05) In NSCLC ,but has negative correlation in benign tissues(p<0.05).[Conclusion]1. The expression of FHIT in NSCLC is decreased, and the decreased expression was closely related with P-TNM staging, squamous cancer's differentation and lymph node metastasis. The low expression of FHIT may participate in lungcarcinogenesis and development of lung cancer. And the low expression of FHIT is related with smoking. FHIT may be the target gene of smoking with lung cancer. The expression of FHIT in squamous is lower in adenocarcinoma, that shows FHIT may be not the key gene in adenocarcinoma carcinogenesis.2. The expression of P21WAF/cip in NSCLC was higher than that in benign tissues and related to tumor differation, smoking and squamous cancer's lymph node metastasis. The P21 waf/c|p might play a role in lung carcinogenesis and development.3. The expression of PCNA were high in lung carcinoma, and were closely related to histologic type, TNM staging and lymph node metastasis. The expression of PCNA in adenocarcinoma is higher than in squamous. From it we can see that PCNA is more important in development than in squamous.4. The defunction of FHIT may affect the function of P21WAF/cip and PCNA, all of three may participate in lung carcinogenesis and development. It may benefits for diagnosis in lung cancer to investigate the three kinds of protein.