The role of SHP-1 promoter 2 hypermethylation detection of lymph node micrometastasis in resectable nonmetastasis NSCLC as a prognostic marker of disease

Abstract

Introduction; Despite adequate surgical management of stage I non-small cell lung cancer, many patients still have relapsed of disease which leads to mortality. Micrometastasis of tumor is the postulate mechanism which might not be detected by standard H&E method. The author conducted the study of epithelial methylation marker, SHP-1 Promoter 2 (SHP1P2) methylation as a potential molecular marker to detect high risk relapsed of disease in stage I resectable non-small cell lung cancer (NSCLC). Method; To explore the potential role of SHP1P2 methylation to detect micrometastasis, Lymph node from resectable NSCLC stage II-IIIA and reactive lymph node were recruited as validate set. Further validation in lymph node from stage I NSCLC was done. AII study participants was underwent curative resection and follow-up at The King Chulalongkorn Memorial Hospital. Stage I NSCLC who had a recurrence within 40 months after resection was defined as high risk patient. Results; Seventy-five lymph nodes in validate set were analyzed. SHP1P2 methylation was significant higher in metastasis lymph node compared with reactive or no metastasis lymph node by H&E method (p=0.008). One hundred and ninety-eight lymph nodes from 23 patients with stage I non-small cell lung cancer was recruited in the analysis. Containing more than 58% of high SHP1P2 methylation in analyzed resected lymph node could be predict high risk of disease, sensitivity 71% and specificity 99% (HR 0.43-1.04; p=0.07). Conclusion; SHP1P2 methylation of resected lymph node of stage I NSCLC treated with curative intent of surgery is associated with early relapsed of disease.