Vershasselt-Crinquette Marie, Colin Pierre, Ouzzane Adil, Gnemmi Viviane, Robin Yves-Marie, Aubert Sebastien, Villers Arnauld, Leroy Xavier
Institute of Pathology, Biology-Pathology Center, Centre Hospitalier Regional Universitaire and University Lille II, Lille, France.
Appl Immunohistochem Mol Morphol. 2012 Jul;20(4):363-6. doi: 10.1097/PAI.0b013e318241cab9.
Upper urinary tract urothelial carcinoma (UUTUC) is an uncommon neoplasm frequently discovered at a high-stage disease. The prognosis of disseminated UUTUCs is poor despite the use of platinum-based chemotherapy. The aim of the study was to evaluate HER2 overexpression and amplification in a series of 83 UUTUCs.
All tumors were formalin fixed. TNM stage, grade, lymphovascular invasion, surgical margins, morphologic variants were reviewed by 2 pathologists. All tumors were immunostained with anti-HER2 antibody. HER2 gene amplification was determined by dual-color in situ hybridization. Gene amplification was defined by an HER2/CEN 17 ratio >2.2.
HER2 immunostaining was observed in 33/83 tumors. Twelve cases were 2+ score and 2 cases were 3+ score. HER2 in situ hybridization was evaluable in 75/83 cases. Amplification was observed in 6 (7%) cases. All amplified tumors were of high grade and 4/6 were stage pT3. A strong correlation between HER2 overexpression and amplification was noted (P<0.0001). HER2 overexpression and amplification were correlated with the pN+ stage but not with specific survival or recurrence.
These results suggest that HER2 amplification is a rare event in UUTUC but may be of interest for targeted therapy in selected high-grade and high-stage tumors.
上尿路尿路上皮癌（UUTUC）是一种不常见的肿瘤，常在疾病晚期被发现。尽管使用了铂类化疗，但播散性UUTUC的预后较差。本研究的目的是评估83例UUTUC中HER2的过表达和扩增情况。
所有肿瘤均用福尔马林固定。两名病理学家对TNM分期、分级、淋巴管浸润、手术切缘、形态学变异进行了评估。所有肿瘤均用抗HER2抗体进行免疫染色。通过双色原位杂交测定HER2基因扩增情况。基因扩增定义为HER2/CEN 17比值>2.2。
83例肿瘤中有33例观察到HER2免疫染色。12例评分为2+，2例评分为3+。83例中有75例可进行HER2原位杂交评估。6例（7%）观察到扩增。所有扩增肿瘤均为高级别，6例中有4例为pT3期。注意到HER2过表达与扩增之间存在强相关性（P<0.0001）。HER2过表达和扩增与pN+期相关，但与特定的生存率或复发无关。
这些结果表明，HER2扩增在UUTUC中是罕见事件，但对于选定的高级别和晚期肿瘤的靶向治疗可能具有意义。
