Tumor protein D52 (TPD52) is overexpressed and a gene amplification target in ovarian cancer.
Recurrent chromosome 8q gain in ovarian carcinoma is likely to reflect the existence of multiple target loci, as the separate gain of chromosome bands 8q21 and 8q24 has been reported in independent studies. Since tumor protein D52 (TPD52) has been identified as a chromosome 8q21 amplification target in breast and prostate carcinoma, we compared TPD52 expression in normal ovarian epithelium (n = 9), benign serous adenomas (n = 11), serous borderline tumors (n = 6) and invasive carcinomas of the major histologic subtypes (n = 57) using immunohistochemistry. These analyses revealed that all normal ovarian epithelium samples and benign serous tumors were predominantly TPD52-negative, whereas TPD52 was overexpressed in most (44/57; 77%) ovarian carcinomas regardless of histologic subtype. TPD52 subcellular localization was predominantly cytoplasmic, although nuclear localization was also frequently observed in mucinous and clear cell carcinomas. In an independent cohort of stage III serous carcinomas (n = 18), we also directly compared in situ TPD52 expression using immunohistochemistry and TPD52 copy number using interphase FISH analyses. This revealed that TPD52 dosage and TPD52 expression were significantly positively correlated. TPD52 therefore represents a novel molecular marker in ovarian cancer, which is broadly expressed across the different histologic subtypes and whose upregulation frequently reflects increased TPD52 copy number.
Byrne
Jennifer A
JA
Molecular Oncology Laboratory, Oncology Research Unit, The University of Sydney Discipline of Paediatrics and Child Health, The Children's Hospital at Westmead, New South Wales, Australia. jennifeb@chw.edu.au
Balleine
Rosemary L
RL
Schoenberg Fejzo
Marlena
M
Mercieca
Janelle
J
Chiew
Yoke-Eng
YE
Livnat
Yael
Y
St Heaps
Luke
L
Peters
Gregory B
GB
Byth
Karen
K
Karlan
Beth Y
BY
Slamon
Dennis J
DJ
Harnett
Paul
P
Defazio
Anna
A
D014408:Biomarkers, Tumor / Q000032:analysis; D018394:CA-125 Antigen / Q000097:blood; D002898:Chromosomes, Human, Pair 8; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D010053:Ovary / Q000737:chemistry
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D009363:Neoplasm Proteins; C114751:TPD52 protein, human