Radiation effects on development of HER2-positive breast carcinomas
Radiation effects on development of HER2-positive breast carcinomas
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DOI：
10.1158/1078-0432.ccr-06-1490
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发表时间：
2007-01-01
影响因子：
11.5
通讯作者：
Tagliabue, Elda
中科院分区：
文献类型：
--
作者：
Castiglioni, Fabio;Terenziani, Monica;Tagliabue, Elda
目的：无论是乳腺癌相关还是遗传学风险因素与高度增殖性HER 2阳性乳腺癌的发展相关。由于大多数HER 2阳性肿瘤存在癌基因的扩增，我们询问辐射引发的基因组不稳定性是否可能参与诱导HER 2过表达乳腺癌。六十-分析了6例浸润性乳腺癌和61例连续散发性乳腺肿瘤的对照组，其中浸润性乳腺癌来自接受放射治疗的霍奇金淋巴瘤或其他儿科实体瘤患者用HercepTest免疫组织化学检测HER 2表达。一组针对雌激素受体、孕激素受体、c-kit、细胞角蛋白5/6、p53和ki 67抗原的抗体也用于鉴定所分析的乳腺癌的分化亚群和分子特征。尽管在HER 2表达评分为2+和3+方面，两个肿瘤系列之间没有发现差异，在乳房成熟期接受放疗的患者中，3+ HER 2阳性肿瘤的百分比显著高于在乳房成熟后接受放疗的患者（35.3%对12.5%，P=0.046）。在后一组中，52.5%的乳腺癌表现出基底样分化（雌激素受体、孕激素受体和HER 2阴性），而在乳腺发育期间接受过放射治疗的乳腺癌中仅有5.9%（P
Purpose: Neither hormone-related nor genetics risk factors have been associated with the development of highly proliferative HER2-positive breast carcinomas. Because the majority of HER2-positive tumors present the amplification of the oncogene, we asked whether genomic instability triggered by irradiation might be involved in the induction of HER2-overexpressing breast carcinomas.Experimental Design: Sixty-six infiltrating breast carcinomas from patients treated with radiation therapy for Hodgkin's lymphoma or other pediatric solid tumors and a control series of 61 consecutive sporadic breast tumors were analyzed by immunohistochemistry for HER2 expression with HercepTest. A panel of antibodies against estrogen receptor, progesterone receptor, c-kit, cytokeratin 5/6, p53, and ki67 antigen was also used to identify differentiation subsets and molecular characteristics of the analyzed breast carcinomas.Results: Although no differences between the two tumor series were found with respect to HER2 expression scored 2+ and 3+, the percentage of 3+ HER2-positive tumors was significantly higher in patients irradiated during breast maturation compared with patients irradiated after breast maturation (35.3% versus 12.5%, P=0.046). In the latter group, 52.5% of the breast carcinomas showed basal-like differentiation (estrogen receptor, progesterone receptor, and HER2 negative) versus only 5.9% in the group irradiated during breast development (P