| Objective: By detection of thymidylate synthase (TS) and breast cancer susceptibility gene l (BRCA1) in 160 cases stageⅠB~ⅢA postoperative non—small cell lung cancer(NSCLC) pathology organization, explore the relationship between the expression of TS and BRCA1 and the patients'clinicopathological characteristics, disease free survival(DFS), Overall survival(OS) in postoperative NSCLC patients.Methods: (1)Retrospective studies 160 cases of the NSCLC(stageⅠB~ⅢA)operated in the First Affiliated Hospital of Dalian Medical University from January 2001 to October 2007.There are 74 cases stage IB, 22 cases stageⅡB, 64 cases stageⅢA.132 cases in the group received chemotherapy and 28 cases didn't. Applied tissue microar-ray (TMA), make the microar-ray paraffin embedded NSCLC pathohistology structure by hand. examined the expression of TS and BRCAl by immunohistochemical method and analyzed the relationship between the TS and BRCA1 expressions and the patients'age,gender,pathological classification,clinical stage(TNM),smoking index,and the relationship of their expressions, analyzed the factors Influencing DFS and OS. (2)Chi-square criterion, life table method and Cox-method were used to analyze those collected data.Results: (1) In 160 cases (stageⅠB~ⅢA) postoperative non-small cell lung cancer (NSCLC) pathology organization, the positive rate of TS expression is 51.9% and BRCA1 is 50.6%.There was no correlation between their expressions. (2) The expression of TS did not show any association with patient age, gender and smoking index. In different types of histopathology, the positive rates of TS expression is the highest in squamous carcinoma, followed by adenocarcinoma, adenosquamous carcinoma is the lowest, the difference was statistically significant (P<0.05);in different types of malignancy degree, as the degree of malignancy increased, the difference was statistically significant (P<0.05);and in different types of clinical stage, the incidence of positive TS was as follows clinical stage, the difference was statistically significant (P<0.05).(3)The positive rates of BRCA1 expression did not show any association with patient age, gender, histopathological grade, histology type, clinical stage and smoking index.(4) In the group of NSCLS patients, the median DFS was 28 months, the median OS was 46 months. In the group with TS negative expressions than positive, the median DFS was extended (50vs22months), the median OS was extended (50vs22months), the difference was statistically significant (P<0.05). In the group with BRCA1 negative expressions than positive, the median DFS was extended (45vs25 months), the median OS was extended (55vs39months), the difference was statistically significant (P<0.05).(5)For the squamous carcinoma, adenocarcinoma, the median DFS and OS were extended of TS negative group than positive, the difference was statistically significant (P<0.05); for the middle and poorly differentiated tumor , the median DFS and OS were extended of TS negative group than positive, the difference was statistically significant (P<0.05);for the stageⅡB~ⅢA, the median DFS and OS were extended of TS negative group than positive, the difference was statistically significant (P<0.05);there are too small number of adenosquamous carcinoma to study; for the highly differentiated tumor and stageⅠ, the difference was not statistically significant.(6)For the squamous carcinoma the median DFS and OS were extended of BRCA1 negative group than positive, the difference was statistically significant (P<0.05); for the middle and highly differentiated tumor , the median DFS and OS were extended of BRCA1 negative group than positive, the difference was statistically significant (P<0.05);for the stageⅠ, the median DFS and OS were extended of BRCA1 negative group than positive, the difference was statistically significant (P<0.05);there are too small number of adenosquamous carcinoma to study; for adenocarcinoma ,the poorly differentiated tumor and stageⅡB~ⅢA, the difference was not statistically significant. (7)In this group, 132 cases of NSCLC patients with adjuvant chemotherapy, the median DFS and OS were extended of TS negative group than positive, the difference was statistically significant (P<0.05), the survival time after disease progression about the patients of TS negative expression group, Second-line chemotherapy with Pemetrexe ,may be extended (16months). (8) BRCA1 expression in patients of postoperative adjuvant chemotherapy for DFS and OS with no significant effect (P>0.05), Of which, BRCA1 negative expression group used GP, NP, TP to adjuvant chemotherapy, their DFS and OS is different, the difference was statistically significant (P<0.05). (9) The Results of Cox multivariate regression analysis: Clinical stage, chemotherapy, TS expression were shown to be independent prognosis factors for DFS and OS of postoperative NSCLC.Conclusions (1) The positive expression of TS was correlated with the pathologic type, the degree of malignancy and the clinical stage. Positive rate in squamous carcinoma is higher than adenocarcinoma, positive rate of TS was concurrently increased with malignant tumors and clinical stage (TNM) increases.(2) There were not significant correlation between the positive rate of BRCA1 and Clinicopathologic Features.(3) Over expressions of TS and BRCA1 have some effects on DFS and OS of stageⅠB ~ⅢA postoperative NSCLC patients. While the expression of TS and BRCA1 were positive, the prognosis was worse. (4) TS might be valuable factors in guiding the chemotherapy and predicting chemotherapy efficacy. In TS negative expressed group, adjuvant chemotherapy could extend their DFS and OS; Second-line chemotherapy with Pemetrexe could extend their OS.(5) For NSCLC patients with adjuvant chemotherapy, the expression of BRCA1 had no significant effects on their DFS and OS.(6) The Results of Cox multivariate regression analysis: Clinical stage, whether chemotherapy, TS expression were shown to be independent prognosis factors for DFS and OS of postoperative NSCLC. |
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