Abstract 1546: Low-molecular-weight protein tyrosine phosphatase is a useful biomarker for predicting postoperative biochemical recurrence in RM0 prostate cancer

Abstract

Abstract Objective: Low-molecular-weight protein tyrosine phosphatase (LMPTP) has a molecular weight of 18 kDa. Studies have shown that the elevated expression of this enzyme is associated with poor prognosis of certain cancers. For prostate cancer, positive surgical margins are considered an important predictor of such recurrences. However, biochemical recurrence is observed even with a negative surgical margin (RM0), and some cases require salvage therapy. Few reports have identified useful biomarkers to predict these cases. In this study, we investigated whether LMPTP expression level could be a biomarker of these recurrences in RM0 prostate cancer. Methods: The subjects were 119 patients who underwent a total prostatectomy with a negative resection margin, at our hospital, between 2007 and 2011. Immunostaining of 2 TMA samples per patient was performed to evaluate LMPTP expression levels. Expression was classified as negative, 0; weak, 1; moderate, 2; or strong, 3 by two pathologists. Each patient was given a total expression score consisting of 13 levels from 0 to 12. By constructing a ROC curve, LMPTP expressions were categorized into either a high expression group (score: ≥5) or a low expression group (score: ≤4). We then examined the relationship of LMPTP expression level with other pathological observations and biochemical recurrence. Cancer survival analysis was performed using the Kaplan-Meier method, log-rank test, and Cox's proportional hazards model. The threshold for statistical significance was set at p < 0.05. Results: Evaluation of immunostained samples by the two pathologists were highly reliable, with an Intraclass correlation (ICC) score for two distinct measurements of 0.77 and 0.98, respectively. 68 patients (57.1%) were categorized in the LMPTP high expression group; and 51 patients (42.9%), in the low expression group. The log-rank test revealed that early biochemical recurrence was observed in the high LMPTP expression group (p = 0.0011). In addition, both the univariate and multivariate analyses revealed that high LMPTP expression level was an independent prognostic factor for biochemical recurrence. Furthermore, in the RM0 cases, high LMPTP expression level (HR:3.62, p = 0.023) was shown to be a better prognostic factor than Gleason score (GS; p = 0.406). Lastly, high LMPTP expression level strongly correlated with the Ki-67 proliferation marker (p < 0.0001), suggesting that LMPTP is expressed in tumor cells with high proliferative capacity. Conclusion: This study suggests that immunostaining of LMPTP is a better predictor of biochemical recurrence than GS in cases of RM0 total prostatectomy. This biomarker can be evaluated with a single immunostaining with high reproducibility, and can therefore be a clinically applicable tool in postoperative follow-ups and as a predictor of recurrence that require salvage therapy. Citation Format: Hirofumi Kurose, Kosuke Ueda, Reiichiro Kondo, Kiyoaki Nishihara, Makoto Nakiri, Mitsunori Matsuo, Shigetaka Suekane, Sakiko Sanada, Sachiko Ogasawara, Tsukasa Igawa, Hirohisa Yano. Low-molecular-weight protein tyrosine phosphatase is a useful biomarker for predicting postoperative biochemical recurrence in RM0 prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1546.