Odicino F E, Bignotti E, Rossi E, Pasinetti B, Tassi R A, Donzelli C, Falchetti M, Fontana P, Grigolato P G, Pecorelli S
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Brescia, Brescia, Italy.
Int J Gynecol Cancer. 2008 Jan-Feb;18(1):14-21. doi: 10.1111/j.1525-1438.2007.00946.x. Epub 2007 Apr 19.
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.
子宫浆液性乳头状癌（USPC）是子宫内膜癌（EC）中一种罕见且高度恶性的类型，其特点是早期转移、化疗耐药及高死亡率。尽管最近有研究提示HER-2/neu在USPC的发生发展中起作用，但关于USPC的肿瘤发生机制仍知之甚少。本研究的目的是通过免疫组织化学（IHC）评估12例经福尔马林固定、石蜡包埋（FFPE）的USPC样本中HER-2的表达情况。此外，我们通过荧光原位杂交（FISH）观察HER-2蛋白表达与HER-2/neu基因扩增之间的相关性，同时通过定量实时逆转录（RT）-聚合酶链反应（PCR）检测HER-2/neu信使RNA的表达。最后，将这些结果与EC患者通常评估的临床特征进行比较，以确定HER-2/neu过表达在USPC中的潜在预后价值。12例患者中有2例（16.6%）经IHC检测显示HER-2蛋白高表达，同样这2例通过FISH检测显示有特异性的HER-2/neu基因扩增。所有检测样本的IHC和FISH数据完全一致。12例肿瘤中有5例（41.6%）显示17号染色体多体性，聚焦于2例显示HER-2/neu过表达的USPC，其中1例（50%）为17号染色体多体性。所有其他USPC病例（58.4%）显示17号染色体为二体性。对所有FFPE USPC样本获得的互补DNA进行定量RT实时PCR检测，结果与FISH和IHC数据完全相关。此外，HER-2/neu过表达与较差的总生存率和极低的无复发生存时间相关，因此被认为是USPC总体预后较差的候选标志物。针对HER-2/neu阳性USPC患者使用曲妥珠单抗（赫赛汀）进行治疗，应在临床试验中进一步研究。
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