Y. Hirose1, J. Sakata1, T. Kobayashi1, K. Takizawa1, K. Miura1, T. Katada1, M. Nagahashi1, Y. Shimada1, H. Ichikawa1, T. Hanyu1, H. Kameyama1, T. Wakai1 1Niigata University Graduate School of Medical and Dental Sciences,Division Of Digestive And General Surgery,Niigata, NIIGATA, Japan
Introduction: NAD (P) H: quinone oxidoreductase – 1 (NQO1) protects human cells against redox cycling and oxidative stress. We hypothesized that immunohistochemical expression of NQO1 in the resected specimen of colorectal liver metastasis (CRLM) has impact on the response to preoperative chemotherapy for CRLM and survival after liver resection in patients with CRLM.
Methods: A retrospective analysis was conducted of 88 consecutive patients who underwent initial liver resection for CRLM from January 2005 through December 2016 in Niigata university medical and dental hospital. The median follow-up time was 65.4 months. Immunohistochemistry was conducted for the resected specimen using a monoclonal anti-NQO1 antibody. According to the NQO1 expression in tumor cells of CRLM, the patients were classified into two groups: the NQO1 positive group and the loss of NQO1 group. According to the NQO1 expression in non-neoplastic epithelial cells of the large intrahepatic bile ducts, the patients were classified into two groups: the NQO1 non-polymorphism group, which had NQO1 expression in those cells, and the NQO1 polymorphism group, which had no NQO1 expression in those cells. Overall survival (OS) after liver resection for CRLM were evaluated by univariate and multivariate analyses taking into consideration 15 other clinicopathological factors. Among 30 patients who received preoperative chemotherapy for CRLM, association between response to preoperative chemotherapy for CRLM and NQO1 status of those patients was evaluated. Response to preoperative chemotherapy was determined according to pathologic response and RECIST criteria using multidetector row CT. All tests were two-sided and P < 0.05 were considered statistically significant.
Results: Of the 88 patients, 61 were classified as the NQO1 positive group and 27 as the loss of NQO1 group, whereas 21 were classified as the NQO1 non-polymorphism group and 67 as the NQO1 polymorphism group. The loss of NQO1 group was associated with a lower prehepatectomy serum CEA level. The NQO1 polymorphism group was associated with higher frequency of bilobar metastases. The loss of NQO1 group had significantly better OS than the NQO1 positive group (cumulative 5-year OS rate: 90.9% vs 66.5%, P = 0.026), and loss of NQO1 expression was an independent favorable prognostic factor in multivariate analysis (relative risk: 0.139, P = 0.001). Regarding association between the response to preoperative chemotherapy for CRLM and NQO1 status, the presence of NQO1 polymorphism was significantly associated with a better response to preoperative chemotherapy in RECIST (P = 0.004). The absence or presence of NQO1 expression in CRLM was not associated with response to preoperative chemotherapy for CRLM.
Conclusion: Loss of NQO1 expression indicates favorable prognosis for patients with CRLM. The presence of NQO1 polymorphism may predict a good response to preoperative chemotherapy for CRLM.