Molecular diagnosis and prognostic significance of lymph node micrometastasis in patients with histologically node-negative non-small cell lung cancer.
Lymph node metastasis is a major prognostic factor in resected non-small cell lung cancer (NSCLC). However, 30-40 % rate of recurrence after performing complete resection in node-negative patients suggests that their nodal staging is suboptimal. We aimed to evaluate the molecular diagnosis and prognostic significance of lymph node micrometastasis in patients with node-negative NSCLC. Primary tumor samples from 62 patients with resected stage I-IIB NSCLC were screened for fragile histidine triad (FHIT) and CDKN2A mRNA deletion using reverse transcriptase polymerase chain reaction (RT-PCR). The molecular alternations were found in tumors of 49 patients. A total of 269 lymph nodes from these 49 NSCLC patients with FHIT or/and CDKN2A deletion tumors were examined. Fifteen positive-control nodes and ten negative-control nodes were also analyzed for FHIT and CDKN2A mRNA deletion. Thirty-nine (22 %) and 22 (18 %) lymph nodes from the 49 patients with FHIT and CDKN2A mRNA deletion in primary tumor had FHIT and CDKN2A mRNA deletion, respectively. The types of FHIT and CDKN2A mRNA deletion in lymph nodes were identical with those in their primary tumors. By combination of two markers, 16 patients (32.7 %) were found to have nodal micrometastasis. Survival analysis showed that patients with nodal micrometastasis had reduced disease-free survival (P = 0.001) and overall survival (P = 0.002) rates. Multivariate analysis demonstrated that nodal micrometastasis was an independent predictor for worse prognosis. Thus, the detection of lymph node micrometastasis by FHIT and CDKN2A mRNA deletion RT-PCR will be helpful to predict the recurrence and prognosis of patients with completely resected stage I-IIB NSCLC.
Department of Medical Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Chun-Hua
CH
Dai
Jian
J
Li
Li-Chao
LC
Yu
Xia-Qin
XQ
Li
Shun-Bing
SB
Shi
Jian-Rong
JR
Wu
D017766:Acid Anhydride Hydrolases / Q000235:genetics; D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D018196:Carcinoma, Adenosquamous / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D061206:Neoplasm Micrometastasis; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000099170:Bis(5'-adenosyl)triphosphatase