Abstract 1700: The prognostic marker SHP-1 promoter 2 hypermethylation can detect lymph node micrometastases in early stage NSCLC

Abstract

Abstract Introduction; Despite adequate surgical management of stage I non-small cell lung cancer, many patients still relapse and die of their disease. Micrometastases within lymph nodes might not be detected by standard H&E method. The authors conducted the study of epithelial methylation marker, SHP-1 Promoter 2 (SHP1P2) methylation as a potential molecular marker to determine its association with a high risk of disease relapse in stage I resectable non-small cell lung cancer (NSCLC). Method; Lymph nodes from resectable NSCLC stage II-IIIA were examined as a test set. All study participants had stage I NSCLC and underwent curative resection during 2001-2007 and had follow-up at The King Chulalongkorn Memorial Hospital, Bangkok, Thailand. No adjuvant treatment was given. Recurrence of disease within 40 months after resection was defined as high risk. Results: In stage II-IIIA, 75 lymph nodes were analyzed. SHP1P2 methylation was significantly higher in lymph nodes containing H&E detectable metastasis compared with histologically negative nodes (p=0.008). One hundred and ninety-eight lymph nodes from 23 patients with stage I non-small cell lung cancer were analyzed in this study. Seven patients (30%) relapsed within 40 months. Median follow-up period from surgery to relapsed of disease or censored if no relapse of disease was 56 months (range 6-109 months). All clinical/pathologic features were similar except for a larger primary tumor size in the early relapse group. Median tumor size is 5 cms (range 2-11.5) vs 2.5 cms (range 1.5-5.7) in high and low risk group respectively. Multivariate logistic-regression analyses included demographic data (sex, age, staging, tumor grading, size, type of surgery and number of resected lymph node) and SHP1P2 methylation status were done. A high absolute level of SHP1P2 methylation (>58%) in analyzed resected lymph node was associated with early relapse, sensitivity 71% and specificity 99% (HR 0.43-1.04; p=0.07 (univariate); p=.002 (multivariate) with an odds ratio of recurrent cancer of 32). Conclusion: SHP1P2 methylation of resected lymph node of stage I NSCLC treated with curative intent of surgery is associated with early relapsed of disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1700. doi:1538-7445.AM2012-1700