Protein Tyrosine Phosphatase 4A2 Expression Predicts Overall and Disease-Free Survival of Human Breast Cancer and Is Associated with Estrogen and Progestin Receptor Status

Abstract

Expression of protein tyrosine phosphatase PTP4A2 (also known as PRL2) has been examined in a variety of human carcinomas, although its role in breast cancer remains inconclusive. Since the majority of previous breast cancer studies utilized tissue biopsies composed of heterogeneous cell populations, we hypothesized that an examination of PTP4A2 expression in carcinoma cells isolated by laser capture microdissection (LCM) would provide a more accurate means of assessing its predictive value. From investigations of 247 human breast cancer biopsies collected under standardized, stringent conditions, total RNA was extracted from LCM-procured carcinoma cells to perform microarray analyses to identify gene signatures associated with breast cancer behavior. Expression of PTP4A2 was corroborated by real-time quantitative polymerase chain reaction (qPCR) and referenced to estrogen and progesterone receptor levels. Patient outcomes for overall and disease-free survival were more favorable (p=0.004 and p=0.001, respectively) when the expression of PTP4A2 in breast carcinomas was increased compared to patients with biopsies with decreased PTP4A2 levels. PTP4A2 expression determined either by microarray or qPCR was elevated in either estrogen receptor (ER)-positive or progestin receptor (PR)-positive breast cancer biopsies compared to ER-negative or PR-negative biopsies. However, PTP4A2 expression was only correlated with overall survival in PRpositive breast carcinomas. These data suggest that PTP4A2 mRNA expression alone may serve as a biomarker for prediction of a breast cancer patient's risk of recurrence and overall survival.

Over-expression of protein tyrosine phosphatase 4A2 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma

“…These finding were consistent with other studies. For example, Zhao et al and Andres et al separately reported the high expression of PTP4A2 protein in human breast cancer, where was positively correlated with tumor aggressiveness and/or advanced clinical stage [ 12 , 22 ]. Our current finding supported that the expression of PTP4A2 increases with NPC progression and this gene may be acted as an oncogene in the development and progression of NPC.…”

“…Similar findings have been reported in the prognostic impact of PTP4A2 on other human cancers, such as human breast cancer [ 12 ] and colony cancer [ 11 ]. In particular, high PTP4A2 expression was found to be related with shorter OS and DFS in breast cancer patients [ 12 , 19 , 22 ]. Our present findings suggested that IHC method, detected as an examination of PTP4A2 expression, could be a reliable tool to predict the prognostic outcome of NPC and make the optimal clinical decisions.…”

The prognostic significance of protein tyrosine phosphatase 4A2 in breast cancer

“…The prognostic significance of PTP4A2 is controversial because some reports suggest that PTP4A2 promotes breast cancer progression, 9 while others suggest that PTP4A2 plays an opposite role suppressing breast cancer progression. 12 , 13 Considering these contradicting reports, we tested the prognostic significance of PTP4A2 in five large breast cancer data sets available in the GEO database. The results are highly consistent between these five breast cancer data sets, showing that a low-level expression of PTP4A2 mRNA was associated with a shorter event-free survival time, therefore suggesting that PTP4A2 expression is a favorable prognostic marker.…”

“…Overexpression of PTP4A2 was shown to promote breast tumor formation in a mouse model. 9 However, two studies 10 , 11 have shown that PTP4A2 was not differentially expressed between normal, benign, and cancerous tissues of the breast, while two other recent publications 12 , 13 demonstrated that increased expression of PTP4A2 was correlated with a favorable overall and disease-free survival. These contradictory findings on the role of PTP4A2 in breast cancer progression led us to investigate the prognostic significance of PTP4A2 gene expression in five publicly available breast cancer data sets, each comprising at least 198 patients.…”

Physiological and oncogenic roles of the PRL phosphatases

“…PRL‐2 was also shown to be elevated in primary breast tumors relative to matched normal tissue, and also higher in metastatic lymph nodes compared to primary tumors . On the other hand, PRL‐2 mRNA expression correlated with better survival in breast cancer patient and high expression of PRL‐2 was a favorable prognostic marker in five independent breast cancer datasets . Still, when PRL‐2 was overexpressed in a breast cancer transgenic mouse model, faster mammary tumor formation was observed .…”