Correlation between NDRG1 and PTEN expression in endometrial carcinoma

Abstract

N-myc Downstream-Regulated Gene 1 (NDRG1) is known as a differentiation-related gene that plays important roles in cell differentiation, organ formation, and embryonic development. NDRG1 has recently been shown to be associated with carcinogenesis and tumor progression in a wide variety of tumors. Phosphatase and tensin homolog deleted from chromosome (PTEN), a phosphatase and tensin homolog located on chromosome 10, is shown to be a tumor suppressor and is often mutated or deleted in various tumor cells, particularly in endometrial carcinoma. Using an immunohistochemical approach, we investigated the expression of NDRG1 and PTEN in normal endometrium, atypical hyperplasia, and endometrial carcinoma. All tumor tissues harvested in this study were derived from endometrioid carcinoma Type I, that were estrogen-related. Our results demonstrate that the expression of NDRG1 was up-regulated in 5/40 (12.5%), 18/34 (52.94%), and 86/103 (83.5%) normal endometrium, atypical hyperplasia, and endometrial carcinoma cases, respectively (P < 0.01), while in 6/40 (15%), 20/34 (58.82%), and 89/103 (86.41%) normal endometrium, atypical hyperplasia, and endometrial carcinoma cases, respectively. PTEN expression was significantly decreased (P < 0.01). Statistical analyzes demonstrated a positive correlation between NDRG1 up-regulation and PTEN down-regulation (P < 0.01). The expression of NDRG1 had no correlation with the differentiation degree of the tumor cells, lymph-node metastasis, and/or abdominal cavity implantation (P > 0.05). Our results indicated that development of endometrial carcinoma is associated with an overexpression of NDRG1 and the loss of PTEN expression. Identification of changes in the NDRG1 and PTEN expression may be a significant diagnostic tool for the early detection of endometrial carcinoma.

Figure 1

Immunolocalization of N‐myc Downstream‐Regulated Gene 1 in normal endometrium, 400× magnification (a) and endometrial carcinoma, 200× magnification (b).

Figure 2

Immunolocalization of N‐myc Downstream‐Regulated Gene 1 was positive in the carcinoma glands (red arrows) while negative in proximal normal glands (green arrows), 200× magnification.

Figure 3

Expression of N‐myc Downstream‐Regulated Gene 1 in squamous metaplasia (black arrow), 200× magnification.

Figure 4

Immunostaining of phosphatase and tensin homolog deleted from chromosome was positive in the normal endometrium (a) and loss in the carcinoma gland (b), 400× magnification.