Clinical Impact of Molecular Positive Lymph Node Status in Colorectal Cancer

Background: Accurate evaluation of lymph node (LN) status is important for prediction of prognosis and decision of postoperative adjuvant therapy in cancer patients. Histopathological diagnosis, usually used for this evaluation, has shortcoming of lower sensitivity due to observing only small portion of whole lymph node. To overcome it we developed a new molecular diagnostic system, one-step nucleic acid amplification (OSNATM) assay which measures cytokeratin (CK) 19 mRNA expression level in whole lymph node and reported the usefulness in colorectal cancer (CRC) as well as in breast, gastric and lung cancers. According to our recent study in CRC, 17.6% of stage II (histologically node negative) patients were found to be molecularly positive in OSNA assay. In this multicenter trial, we investigated the clinical impact of OSNA positive cases. Methods: Patients with cN0 and cN1 CRC in 11 Japanese representative medical institutes were enrolled. All LNs were examined histopathologically by using one-slice hematoxylin-eosin staining. In addition, half of the LN, which could be cut into half (average, 9.8 LN/patient), was examined by OSNA assay. Patients were classified in accordance with the UICC staging criteria and OSNA results, and the 3-year disease-free survival (DFS) of each cohort was analyzed. Results: We enrolled 204 patients with CRC, excluded 9 patients, and analyzed 195 patients (stage I: n = 50, stage II: n = 71, stage III: n = 74). Of the patients with node-negative CRCs, only one was OSNA positive at stage I, and 11 were OSNA positive at stage II. OSNA-positive stage II cases had much lower 3-year DFS rate than OSNA negative ones (p = 0.005). Among various clinical and pathological parameters, only OSNA status was a significant prognostic factor for 3-year DFS in stage II CRC cases (p = 0.025). Conclusions: This prospective multicenter study showed for the first time a prognostic value of OSNA positivity in stage II CRC. This assay is useful for selecting high-risk patients with stage II CRC. Further study to determine the treatment strategy for patients with OSNA-positive stage II CRC is necessary. Legal entity responsible for the study: OICI Funding: None Disclosure: All authors have declared no conflicts of interest.