The Study About The Rule Of Nodal Occult Micrometastasis In Stage Ⅰ Non-small-cell Lung Cancer

BACKGROUND & OBJECTIVE: The rate of 5-year survival of stageⅠnon-small-cell lung cancer(NSCLC) is 60 %-70 % after radical operation, approximately 30% cases may recurrent two or three years later. Routine histopathologic examination of resected lymph nodes in patients with stage I non-small cell lung cancer may underestimate the incidence of advanced disease. The presence of occult lymph node metastases may be a main factor of recurrence and transference after intended curative resection. This study was designed to detect occult micrometastatic tumor cells in the lymph nodes (LNs) in stage I non–small-cell lung cancer patients using multicytokeratin (MCK) as a micrometastatic marker. The following questions were to be discussed in order to guide clinical therapy. (1) The rate of nodal micrometastasis. (2)By Logistic regression analysis to deduce the main factor that affected micrometastasis from following aspects: age, gender, tumor size, histological types, location, cells differentiation and pathologic T-stage. (3) The method and order of micrometastasis. MATERIALS & METHODS: A total of 91 hilar and 91 subcarinal LNs were removed during surgery from 91 patients with completely resected stage I NSCLC. The standards of selection were as follows: (1) NSCLC; (2) Routine pathologic stage was T1N0M0 and T2N0M0. (3) Without chemoradiotherapy before operation. With another 45 hilar LNs were removed from benign pulmonary lesion patients and 45 hilar LNs which were negative by conventional histopathologic examination and removed from Ⅱand Ⅲstage lung cancer patient as control. The LNs were analyzed for micrometastasis using immunohistochemistry(SP method) with the monoclonal anti-CK antibody AE1/AE3. RESULTS: Micrometastasis was detected in all lymph nodes that were removed from Ⅱand Ⅲstage lung cancer patient, but no one in lymph nodes that were removed from benign pulmonary lesion patients. The rate of micrometastasis in Ⅰstage NSCLC was 49%(45/91), in which squamous cell carcinoma was 47%(28/59) and adenocarcinoma was 53%(17/32), no significant difference between them; The micrometastasis frequency of tumor size≤3cm ﹙20%,7/35)was significantly (x2=22.79 P<0.05﹚lower than that of patients>3cm. ﹙68% 38/56﹚. The micrometastasis frequency of well-differentiated, moderate-differentiated, poor-differentiated carcinoma were 8%(1/12),38%(18/48)and 84%(26/31)respectively, (x~2=25.6,P<0.05﹚The micrometastasis rates of IA stage and IB stage were 13%(4/31)and 68%(41/60)respectively, ﹙x~2=25.12, P<0.05﹚,The micrometastasis frequency of hilar LNs 43% (39/91) was significantly ﹙x~2=21.61, P < 0.05 ﹚higher than subcarinal LNs 12%(11/91). The unvariate analysis showed that tumor size, cell differentiation and T stage may be the adverse factors for nodal micrometastasis, odd ratios (ORs) were 8.4(95%CI: 3.1-22.9), 6.9(95%CI: 2.8-16.9) and 14.5(95%CI: 4.46-47.52 ) respectively. The multivariate analysis indicated that cell differentiation and T stage may be the adverse factors for nodal micrometastasis, odd ratios (ORs) were 7.028(95%CI: 2.49-19.80) and 14.50(95%CI: 3.80-55.38) respectively. CONCLUSION: There were nodal micrometastasis in completely resected stage I NSCLC patients. The micrometastasis frequency of IB stage was significantly higher than IA stage; It was necessary for IB stage NSCLC to be given chemotherapy after operation; Cell differentiation and T stage may be the adverse factors for nodal micrometastasis. The method of lymph node micrometastasis was from hilum to mediastinum. The skip micrometastasis may be taken place in adenocarcinoma.