Tumor protein D52 (TPD52) is overexpressed and a gene amplification target in ovarian cancer

被引:80
作者
Byrne, JA
Balleine, RL
Fejzo, MS
Mercieca, J
Chiew, YE
Livnat, Y
St Heaps, L
Peters, GB
Byth, K
Karlan, BY
Slamon, DJ
Harnett, P
Defazio, A
机构
[1] Univ Sydney Discipline Paediat & Child Hlth, Oncol Res Unit, Oncol Mol Lab, Childrens Hosp Westmead, Westmead, NSW 2145, Australia
[2] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Westmead, NSW, Australia
[3] Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Sch Med, Los Angeles, CA USA
[4] Childrens Hosp Westmead, Div Res, Westmead, NSW, Australia
[5] Westmead Hosp, Dept Gynecol Oncol, Westmead, NSW 2145, Australia
[6] Westmead Hosp, Dept Med Oncol & Palliat Care, Westmead, NSW 2145, Australia
[7] Childrens Hosp Westmead, Dept Cytogenet, Westmead, NSW, Australia
[8] Westmead Millenium Inst, Westmead, NSW, Australia
[9] Cedars Sinai Med Ctr, Div Gynecol Oncol, Los Angeles, CA 90048 USA
关键词
tumor protein D52; n8; r10; cspp28; crhsp28; chromosome; 8q21; ovarian carcinoma;
D O I
10.1002/ijc.21250
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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 inummohistochemistry 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. (c) 2005 Wiley-Liss, Inc.
引用
收藏
页码:1049 / 1054
页数:6
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