MAL2 and tumor protein D52 (TPD52) are frequently overexpressed in ovarian carcinoma, but differentially associated with histological subtype and patient outcome

Abstract

BackgroundThe four-transmembrane MAL2 protein is frequently overexpressed in breast carcinoma, and MAL2 overexpression is associated with gain of the corresponding locus at chromosome 8q24.12. Independent expression microarray studies predict MAL2 overexpression in ovarian carcinoma, but these had remained unconfirmed. MAL2 binds tumor protein D52 (TPD52), which is frequently overexpressed in ovarian carcinoma, but the clinical significance of MAL2 and TPD52 overexpression was unknown.MethodsImmunohistochemical analyses of MAL2 and TPD52 expression were performed using tissue microarray sections including benign, borderline and malignant epithelial ovarian tumours. Inmmunohistochemical staining intensity and distribution was assessed both visually and digitally.ResultsMAL2 and TPD52 were significantly overexpressed in high-grade serous carcinomas compared with serous borderline tumours. MAL2 expression was highest in serous carcinomas relative to other histological subtypes, whereas TPD52 expression was highest in clear cell carcinomas. MAL2 expression was not related to patient survival, however high-level TPD52 staining was significantly associated with improved overall survival in patients with stage III serous ovarian carcinoma (log-rank test, p < 0.001; n = 124) and was an independent predictor of survival in the overall carcinoma cohort (hazard ratio (HR), 0.498; 95% confidence interval (CI), 0.34-0.728; p < 0.001; n = 221), and in serous carcinomas (HR, 0.440; 95% CI, 0.294-0.658; p < 0.001; n = 182).ConclusionsMAL2 is frequently overexpressed in ovarian carcinoma, and TPD52 overexpression is a favourable independent prognostic marker of potential value in the management of ovarian carcinoma patients.

Tumor protein D52 represents a negative regulator of ATM protein levels

“…19 TPD52 promotes proliferation, migration/invasion, and metastasis in different cell models, 17,20,21 whereas knockdown of TPD52 induced apoptosis in breast and prostate cancer cell lines. 17,22 The underlying mechanisms are not yet fully understood, apart from the regulation of Akt/protein kinase B and Stat3/Bcl-2 signaling pathways shown in prostate cancer cell lines.…”

Genome‐wide analysis of recurrent copy‐number alterations and copy‐neutral loss of heterozygosity in head and neck squamous cell carcinoma

“…In these HNSCC samples, we identified another area of recurrent gain interesting the chromosomal region 8q21.1, whose significance is less clear . It is the first time that recurrent gain at 8q21.1 is reported in HNSCC, even if it has been already documented in colorectal cancer , breast carcinoma melanoma , prostate cancer , and ovarian carcinoma .…”

“…It is the first time that recurrent gain at 8q21.1 is reported in HNSCC, even if it has been already documented in colorectal cancer (21), breast carcinoma (22) melanoma (23), prostate cancer (24), and ovarian carcinoma (25). The most interesting candidate target gene harbored in this area is the 'tumor protein D52 isoform 2′ (TPD52, 8q21.13), overexpressed in different types of cancer (25), and even if its physiological function is still under investigation, it is likely to perturb fundamental cell functions common to different cell types, such as the regulation of apoptosis and proliferation. The other recurrent region of gain in HNSCC samples, at 8q23.1-q24.…”

“…The most interesting candidate target gene harbored in this area is the ‘tumor protein D52 isoform 2′ ( TPD52 , 8q21.13), overexpressed in different types of cancer , and even if its physiological function is still under investigation, it is likely to perturb fundamental cell functions common to different cell types, such as the regulation of apoptosis and proliferation. The other recurrent region of gain in HNSCC samples, at 8q23.1‐q24.22, has previously been reported in malignant tumors including oral squamous cell carcinoma.…”

Novel prognostic markers revealed by a proteomic approach separating benign from malignant insulinomas

“…32,33 Overexpression of TPD52 has been described in malignant tumors such as ovarian, prostate and breast cancer, and testicular germ cell tumors. 34,35 As TPD52 was strongly expressed not only in benign insulinomas but also in normal islets, malignant insulinomas probably undergo loss of TPD52 during neoplastic transformation. At present, it is unclear how this finding relates to the malignant potential of insulinomas.…”