MAL2 and tumor protein D52 (TPD52) are frequently overexpressed in ovarian carcinoma, but differentially associated with histological subtype and patient outcome
1 Molecular Oncology Laboratory, Children's Cancer Research Unit, The Children's Hospital at Westmead, Westmead, New South Wales, Australia
2 The University of Sydney Discipline of Paediatrics and Child Health, The Children's Hospital at Westmead, New South Wales, Australia
3 Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia
4 Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
5 Discipline of Pathology, The University of Sydney, Camperdown, New South Wales, Australia
6 South East Area Laboratory Service, Prince of Wales Hospital, Randwick, New South Wales, Australia
7 Westmead Institute for Cancer Research, The University of Sydney at Westmead Millennium Institute, Westmead, New South Wales, Australia
8 Department of Gynaecological Oncology, Westmead Hospital, Westmead, New South Wales, Australia
9 Gynaecological Cancer Centre, Royal Hospital for Women, Randwick, New South Wales, Australia
10 School of Women's and Children's Health, University of New South Wales, Randwick, Australia
11 St Vincent's Clinical School, University of NSW, Sydney, New South Wales, Australia
BMC Cancer 2010, 10:497 doi:10.1186/1471-2407-10-497Published: 17 September 2010
The 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.
Immunohistochemical 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.
MAL2 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).
MAL2 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.