Assessment of HER-2 status in pancreatic adenocarcinoma - Correlation of immunohistochemistry, quantitative real-time RT-PCR, and FISH with aneuploidy and survival
Assessment of HER-2 status in pancreatic adenocarcinoma - Correlation of immunohistochemistry, quantitative real-time RT-PCR, and FISH with aneuploidy and survival
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DOI：
10.1097/01.pas.0000160979.85457.73
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发表时间：
2005-09-01
影响因子：
5.6
通讯作者：
Smith, RC
中科院分区：
文献类型：
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作者：
Saxby, AJ;Nielsen, A;Smith, RC
HER-2是一种跨膜生长因子受体，在几种癌症中被认为是一种独立的不良预后因子。本研究在基因、转录和翻译水平上检测胰腺癌HER-2过表达。根据分期、分级和生存率来衡量表达。应用免疫组化法检测30例胰腺癌组织中HER-2蛋白的表达，实时定量逆转录聚合酶链反应（Q-RT-PCR）检测HER-2 mRNA的表达，荧光原位杂交（FISH）检测HER-2基因的表达。HER-2在胰腺良性病变中的表达（n = 10）提供对照。5例胰腺癌（17%）的免疫组化（IHC）标记评分最高为3+，7例（23%）HER-2 mRNA表达显著增加，而仅1例（3%）显示低水平HER-2基因扩增。10例（33%）肿瘤表现为非整倍体。总体而言，方法之间的一致性较差，但FISH非整倍体状态和Q-RT-PCR mRNA过表达之间的一致性最好（80%一致性），其次是IHC和Q-RT-PCR（73%一致性）。IHC和FISH非整倍体状态之间的一致性最低（67%一致性）。肿瘤分期与HER-2 mRNA和蛋白表达呈正相关，但肿瘤分级和其他患者特征未达到统计学意义。在所有三种过度表达的测量中，HER-2状态均为阳性的患者的生存结局较差（Kaplan-Mejer对数秩评分; P < 0.01 [IHC]，P = 0.05 [Q-RT-PCR]，P = 0.02 [FISH]）。在细胞核、细胞质和细胞表面水平表达的不一致性突出了单独免疫组化评价的局限性，并强调需要进一步评价在基因拷贝、mRNA和受体蛋白过表达的肿瘤中对抗HER-2靶向治疗的反应。
HER-2 is a transmembrane growth factor receptor recognized in overexpression as an independent adverse prognostic factor in several cancers. This study measured HER-2 overexpression in pancreatic adenocarcinoma at the genetic, transcriptional, and translational level. Expression was gauged with regard to stage, grade, and survival. Pancreatic adenocarcinorna samples (n = 30) were analyzed with immunchistochemical labeling for HER-2 protein, Quantitative real-time reverse transcriptase polymerase chain reaction (Q-RT-PCR) measurement of HER-2 mRNA and fluorescence in situ hybridization (FISH) analysis of HER-2 gene expression. HER-2 expression in benign pancreatic lesions (n = 10) provided a control. Five (17%) of the pancreatic adenocarcinomas scored maximal 3+ immunohistochemistry (IHC) labeling, seven (23%) had significantly increased expression of HER-2 mRNA, while only one (3%) exhibited low level HER-2 gene amplification. Ten (33%) tumors demonstrated aneuploidy. In general, concordance between methodologies was poor, but the best agreement was seen between FISH aneuploidy status and Q-RT-PCR mRNA overexpression (80% agreement), followed by IHC and Q-RT-PCR (73% agreement). The least agreement was seen between IHC and FISH aneuploidy status (67% agreement). Tumor stage was positively associated with HER-2 mRNA and protein expression, but tumor grade and other patient characteristics did not reach statistical significance. A poor survival outcome was demonstrated with positive HER-2 status in all three measures of overexpression (Kaplan-Mejer log-rank score; P < 0.01 [IHC], P = 0.05 [Q-RT-PCR], P = 0.02 [FISH]). Discordance in expression at the nuclear, cytoplasmic, and cell surface levels highlights the limitations of immunohistochemical evaluation alone and stresses the need for further evaluation of response to anti-HER-2 targeted therapies in tumors displaying overexpression in gene copy, mRNA, and receptor protein.