P1.12 PGRMC1 as a Predictive Marker for Platinum Resistance in Non-Small Cell Lung Cancer (NSCLC) Patients

Abstract

ABSTRACT Background Treatment of NSCLC is based on platinum included chemotherapy, however its efficacy is not satisfactory because of tumor resistance. Revealing molecular predictive markers of platinum resistance will allow of chemotherapy personalization and avoiding toxic ineffective treatment. Recent studies in vitro have shown that one of the reasons of platinum resistance can be overexpression of the progesterone receptor membrane component-1 (PGRMC1). To answer the question if this resistance mechanism can be realized in cancer patients we have studied level and frequency of PGRMC1 expression in NSCLC tissues. Materials and methods Surgical biopsy specimens of smoking male patients with squamous cell carcinoma (40) and adenocarcinoma (20) were analyzed by flowcytometry. Primary antibodies: rabbit polyclonal IgG to PGRMC1; secondary antibodies: FITC-conjugated goat polyclonal to rabbit IgG (Abcam). Mean number of specifically stained cells were analyzed by Kolmogorov-Smirnov statistical approach. Two indexes of PGRMC1 expression were used: high level - PGRMC1 was revealed in 20-50% of the cells, low - less than in 20%. Results 1. PGRMC1 expression (specific fluorescence more than 10% of the cells) was revealed in 70% of NSCLC patients. High level (29,9 ± 8,1%) was in 36% of the tumors, 67% of which were adenocarcinomas. Low level (14,8 ± 2,4%) was in 64% of the tumors, 81% of which were squamous cell carcinomas.2. In squamous cell carcinomas mean PGRMC1 level was 15%, but in adenocarcinomas - 1,7 times higher (26%, p = 0,013).3. In patients with squamous cell carcinoma low level PGRMC1 was revealed in 81% of cases, high - in 19% only. In contrast, in adenocarcinoma patients high PGRMC1 level was revealed in 67%, but low - in 33%. Conclusion PGRMC1 expression was revealed in the majority of NSCLC patients. In adenocarcinomas mean PGRMC1 level and frequency of high level of PGRMC1 expression were about 2-3 times higher than in squamous cell carcinomas. Taking into account our results and clinical observations that squamous histologic features as compared with adenocarcinomas is significant factor associated with improved survival platinum included chemotherapy, we believe that PGRMC1 could be predictive marker of platinum resistance in NSCLC patients. Supported by RFBR (Grants 10-04-00551-?, 12-04-00028-a).