Organic cation transporter 2 for predicting cisplatin-based neoadjuvant chemotherapy response in gastric cancer

Abstract

Some studies have shown the usability of neoadjuvant chemotherapy (NAC) in gastric cancer (GC). Nevertheless there are a few predictive markers of the effectiveness of NAC in GC. The aim of this study is to assess the predictive impact of organic cation transporter 2 (OCT2) expression on response to neoadjuvant chemotherapy (NAC) in gastric cancer. We retrospectively assessed 66 patients with advanced gastric cancer received NAC with S-1/cisplatin or paclitaxel/cisplatin. Expression levels of OCT2 were assessed by immunohistochemistry in pre-chemotherapy biopsies and correlated with clinicopathologic parameters including pathologic response. High expression level of OCT2 (OCT2(high)) was significantly associated with intestinal type according to Laurén classification (P = 0.03) and low histologic grade (P = 0.03). In univariate analysis of the entire cohort, no variables showed any significant association with a response, although intestinal type (P = 0.09), low histologic grade (P = 0.09), and OCT2(high) (P = 0.07) tended to be more frequent in responders compared with non-responders. When the two treatment groups were separately assessed in the univariate analysis, a significantly higher rate of OCT2(high) was observed in responders compared with non-responders in the S-1/cisplatin group (P = 0.001). In addition, multivariate analysis identified OCT2(high) as the sole independent predictor of response (P = 0.04). However, in the paclitaxel/cisplatin group, no variables were associated with response. Taken together, our results suggest that OCT2(high) may represent a potential predictor of response to NAC with S-1/cisplatin in gastric cancer.

Keywords: Organic cation transporter 2; S-1 plus cisplatin; gastric cancer; immunohistochemistry; neoadjuvant chemotherapy.

Figure 1

Association between OCT2 expression level and pathologic response to NAC with S-1/CDDP. A: A significantly higher rate of OCT2^high was detected in responders (black bar) compared with non-responders (gray bar) in the S-1/CDDP group (P = 0.001). However, no variables were associated with response in the PTX/CDDP group. B: OCT2 immunostaining of a biopsy specimen from a responder showing OCT2^high status. Strong staining was observed in the cell membrane of a number of tumor cells. C: OCT2 immunostaining of a biopsy specimen from a non-responder showing OCT2^low status. Only a few of the tumor cells showed positive staining. *P = 0.001; CDDP: csiplatin; PTX: paclitaxel; Res: responder; Non-res: non-responder; Prox: proximal localization; Intes: intestinal type.