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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Byrne
Jennifer A
JA
Molecular Oncology Laboratory, Children's Cancer Research Unit, The Children's Hospital at Westmead, Westmead, New South Wales, Australia. JennifeB@chw.edu.au
Maleki
Sanaz
S
Hardy
Jayne R
JR
Gloss
Brian S
BS
Murali
Rajmohan
R
Scurry
James P
JP
Fanayan
Susan
S
Emmanuel
Catherine
C
Hacker
Neville F
NF
Sutherland
Robert L
RL
Defazio
Anna
A
O'Brien
Philippa M
PM
D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism* / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D015331:Cohort Studies; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011510:Proteolipids / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis; D033921:Vesicular Transport Proteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; C438606:MAL2 protein, human; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D009363:Neoplasm Proteins; D011510:Proteolipids; C114751:TPD52 protein, human; D033921:Vesicular Transport Proteins