Low-molecular-weight Protein Tyrosine Phosphatase Is a Possible Biomarker for Predicting Postoperative Biochemical Recurrence in Prostate Cancer With Negative Surgical Margins

Abstract

Background/Aim: For prostate cancer, positive surgical margins are considered an important predictor of biochemical recurrence. However, biochemical recurrence is observed in approximately 20% of cases, even with negative surgical margins, and some cases require salvage therapy. The elevated expression of low-molecular-weight protein tyrosine phosphatase (LMW-PTP, MW 18 kDa) is associated with a poor prognosis of certain cancers. In this study, we investigated whether the LMW-PTP expression levels could be used as a biomarker of recurrence in prostate cancer with negative surgical margins. Materials and Methods: The subjects of this retrospective study were 119 patients who underwent total prostatectomy with negative resection margins. LMW-PTP expression was categorized either as a highexpression group or as a low-expression group bye two pathologists. Subsequently, we examined the relationship between LMW-PTP expression levels and clinicopathological factors including biochemical recurrence. Results: Evaluation of the immunostained samples by two pathologists was highly reliable, with an Intraclass correlation (ICC) score for two distinct measurements of 0.77 and 0.98, respectively. Seventythree patients (61.3%) were placed in the LMW-PTP high expression group; and 46 patients (38.7%) were placed in the low expression group. The log-rank test revealed early biochemical recurrence in the high LMW-PTP expression group (p=0.0001). In addition, pathological T stage (p=0.004), lymphatic invasion (p=0.0456), Ki-67 labeling index (p=0.0002), and biochemical recurrence (p<0.0001) were more frequently identified in the LMW-PTP high expression group. Furthermore, multivariate analyses revealed that a high LMW-PTP expression level was an independent prognostic factor for biochemical recurrence (HR=3.14, 95% CI=1.37-8.07, p=0.0057). In addition, Ki-67 labeling indices were significantly higher in the high-expression group compared to the low-expression group (p<0.0001). Conclusion: LMW-PTP can be assessed using a single immunostaining protocol in a highly reproducible fashion. Tt may, thus, be applied clinically to establish the required postoperative follow-up period and determine the necessity for salvage therapy in cases of prostate cancer with negative surgical margins. LMW-PTP has the potential to be a highly useful prognostic biomarker and a therapeutic target in conjunction with other factors, such as the Gleason Score, the pathological T stage and the PSA level.Prostate cancer is the most common type of cancer in men in developed countries. In the United States, one in five new cases of diagnosed cancer is in the prostate, while in Japan, the increasingly widespread use of prostate-specific antigen (PSA) testing has led to prostate cancer becoming the most prevalent type of cancer in men in 2016 (1). Treatment options for localized prostate cancer include radical prostatectomy (2), radiotherapy (external & internal radiation) (3), and active surveillance (4). However, changes in surgical procedures (from open surger...

Elevated Expression of EPHA2 Is Associated With Poor Prognosis After Radical Prostatectomy in Prostate Cancer

“…In contrast, in malignant cells, EPHA2 is not tyrosine phosphorylated, partly because of the inability to bind to its membrane-anchored ligand as a result of the unstable cell-cell contacts in malignant cells. Recently, we reported that low-molecular-weight protein tyrosine phosphatase (LMW-PTP) has potential as a highly useful prognostic biomarker in PCa (22). LMW-PTP is an important negative regulator of EPHA2 phosphorylation, being involved in the proliferation, invasion, and migration of tumors, through the dephosphorylation of EPHA2 (23)(24)(25).…”

Protein Tyrosine Phosphatases in Tumor Progression and Metastasis: Promoter or Protection?

“…In the same study, 147 patients out of 481 with prostate cancer presented higher expression of LMWPTP and worse clinical outcome [34]. Accordingly, the LMWPTP has been categorized as a potential biomarker for recurrence prediction for prostate cancer [35]. The importance of the LMWPTP in cancer progression was also reported in colorectal cancer.…”

Low molecular weight protein tyrosine phosphatase as signaling hub of cancer hallmarks

“…In the same study, 147 patients out of 481 with prostate cancer presented higher expression of LMWPTP and worse clinical outcomes [10]. Accordingly, the LMWPTP has been categorized as a potential biomarker for recurrence prediction for prostate cancer [51].…”