Prognostic value of genetically diagnosed lymph node micrometastasis in non-small cell lung carcinoma cases

The predictive value of lymph node micrometastasis, detected by immunohisto chemical or genetic methods, is well appreciated in terms of prognosis. How ever, a major problem is high false-positive rates, because most methods fo cus on cytokeratin, which is a component not only of carcinoma but also nor mal epithelial and nonepithelial cells. Mutant allele-specific amplificatio n (MASA) can detect DNAs derived from cancer cells itself, reportedly with high sensitivity. It was, therefore, used with nested-PCR using p53 or K-ra s mutation for analysis of lymph node micrometastasis in non-small cell lun g carcinoma (NSCLC) patients in the present study, in comparison with the i mmunohistochemical method using an anti-cytokeratin reagent for the same sa mples. Lymph nodes from 31 NSCLC patients with p53 and K-ras mutated tumors (30 and 1, respectively) staged as pathological (p)-T1-4 N0-1 and M-0 were examined. Genetic and immunohistochemical methods demonstrated positive re actions in 34 (15%) and 61 (27%) of 229 lymph nodes, respectively (9 cases, 29%, and 24 cases, 77%), The concordance with the two methods was 77%, but 13 (39%) of 34 genetically positive lymph nodes could not be detected by i mmunohistochemistry (IHC). Of 22 cases with p-N-0 disease, 6 (27%) were gen etically positive in hilar and/or mediastinal lymph nodes, and 4 (67%) of t hem died after cancer relapse, In contrast, none of the patients without mi crometastasis died of cancer (P < 0.001, log rank analysis). Of the same p- N-0 patients, 17 (77%) were positive by IHC, and 4 (24%) of them died of ca ncer, whereas 5 negative patients did not suffer cancer relapse. Survival d id not significantly differ between cases positive and negative (P = 0.246) by IHC. According to the g-N (N factor restaged by a genetic method), pati ents with g-N, and g-N, disease had a shorter survival than those with g-N- 0 disease (P = 0.042 and P < 0.001, respectively). However, no significant difference was observed with grading by IHC, Thus, detection of micrometast asis in regional lymph nodes with the MASA method, in other words with a ca rcinoma-specific marker, is of greater prognostic significance for early st age NSCLC patients than immunohistochemical results. This approach should f acilitate selection of patients for whom postoperative adjuvant chemotherap y should be performed.