HER-2/neu overexpression and amplification in uterine serous papillary carcinoma:: comparative analysis of immunohistochemistry, real-time reverse transcription-polymerase chain reaction, and fluorescence in situ hybridization

被引:54
作者
Odicino, F. E. [1 ]
Bignotti, E. [1 ]
Rossi, E. [2 ]
Pasinetti, B. [1 ]
Tassi, R. A. [1 ]
Donzelli, C. [2 ]
Falchetti, M. [2 ]
Fontana, P. [3 ]
Grigolato, P. G. [2 ]
Pecorelli, S. [1 ]
机构
[1] Univ Brescia, Dept Obstet & Gynecol, Div Gynecol Oncol, Brescia, Italy
[2] Univ Brescia, Dept Pathol, Brescia, Italy
[3] Hosp Desenzano Garda, Dept Pathol, Brescia, Italy
关键词
Her-2/neu; real-time PCR; uterine serous papillary carcinoma;
D O I
10.1111/j.1525-1438.2007.00946.x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Uterine serous papillary carcinoma (USPC) is a rare and highly malignant form of endometrial cancer (EC) characterized by early metastasis, chemoresistance, and high mortality rate. Little is known about USPC tumorigenesis even if recently a HER-2/neu role has been suggested in its development and progression. The aim of the present study was to evaluate HER-2 expression by immunohistochemistry (IHC) in 12 USPC formalin-fixed, paraffin-embedded (FFPE) samples. Moreover, we looked at the correlation between HER-2 protein expression and HER-2/neu gene amplification by fluorescence in situ hybridization (FISH), other than HER-2/neu messenger RNA expression by quantitative real-time reverse transcription (RT)-polymerase chain reaction (PCR). Finally, these results have been compared with commonly evaluated clinical features in EC patients, in order to define the potential prognostic value of HER-2/neu overexpression in USPCs. A high expression of HER-2 protein by IHC was noted in 2 of 12 patients (16.6%), and the same cases showed specific HER-2/neu gene amplification by FISH. All the samples investigated displayed a perfect concordance between IHC and FISH data. Five (41.6%) of 12 tumors demonstrated polysomy of chromosome 17 and, focusing on the 2 USPCs that showed HER-2/neu overexpression, one of them (50%) was polysomic for chromosome 17. All the other USPC cases (58.4%) showed to be disomic for chromosome 17. Quantitative RT real-time PCR performed on complementary DNA obtained from all FFPE USPC samples showed a complete correlation with FISH and IHC data. Moreover, HER-2/neu overexpression was associated with a poorer overall survival and a very low relapse-free survival time, thus being considered a candidate marker of worse overall prognosis in USPC. The use of trastuzumab (Herceptin), a monoclonal antibody directed against HER-2/neu, for the therapy of patients with HER-2/neu-positive USPCs should be further investigated in clinical trials.
引用
收藏
页码:14 / 21
页数:8
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