Clinical Experimental Oncology Laboratory, National Cancer Centre, Viale Orazio Flacco, 65-70124 Bari, Italy.
Hum Pathol. 2011 Nov;42(11):1589-95. doi: 10.1016/j.humpath.2011.01.010. Epub 2011 Apr 14.
The aim of this study is to evaluate the analysis of markers related with progression, to further characterize familial breast cancers. Here, we investigated the expression of breast cancer susceptibility gene-1, hypoxia-inducible factor-1α, vascular endothelial growth factor receptor 1, and Na+/H+ exchanger regulatory factor 1 in 187 microarrayed breast carcinomas from 94 familial and 93 sporadic breast cancer patients by immunohistochemical staining. Furthermore, the expression levels of these biomarkers were compared with triple-negative phenotype. Familiarity was significantly associated with younger age (P < .000), higher tumor grade (P = .038), negative estrogen receptor hormonal status (P = .036), and high proliferative activity (P = .029). The familial cancers were immunonegative for membranous Na+/H+ exchanger regulatory factor 1 expression compared with sporadic cancers (P = .001); notably, vascular endothelial growth factor receptor 1 staining correlated with cytoplasmic Na+/H+ exchanger regulatory factor 1 expression in familial tumors (P = .009). In multivariate analysis, the "new biomarkers," including negative human epidermal growth factor receptor 2 status (odds ratio, 4.538; 95% confidence interval, 1.756-11.728), negative membranous Na+/H+ exchanger regulatory factor 1 expression (odds ratio, 7.686; 95% confidence interval, 1.876-31.483) and positive nuclear breast cancer susceptibility gene-1 (odds ratio, 0.3982; 95% confidence interval, 0.169-0.936), significantly correlated with family history of breast cancer. We hypothesize that the evaluation of human epidermal growth factor receptor 2, Na+/H+ exchanger regulatory factor 1, and breast cancer susceptibility gene-1 could be clinically useful to identify familial breast tumors and to select patients candidate to breast cancer susceptibility genes 1/2 gene sequencing.
本研究旨在评估与进展相关的标志物分析，以进一步对家族性乳腺癌进行特征描述。在这里，我们通过免疫组织化学染色研究了 94 例家族性和 93 例散发性乳腺癌患者的 187 例微阵列乳腺癌中乳腺癌易感基因 1、缺氧诱导因子 1α、血管内皮生长因子受体 1 和 Na+/H+交换调节因子 1 的表达。此外，还比较了这些生物标志物的表达水平与三阴性表型的关系。家族性与年轻的年龄（P <.000）、较高的肿瘤分级（P =.038）、阴性雌激素受体激素状态（P =.036）和高增殖活性（P =.029）显著相关。与散发性癌症相比，家族性癌症的膜 Na+/H+交换调节因子 1 表达呈免疫阴性（P =.001）；值得注意的是，家族性肿瘤中血管内皮生长因子受体 1 染色与细胞质 Na+/H+交换调节因子 1 表达相关（P =.009）。多变量分析显示，包括人表皮生长因子受体 2 状态阴性（优势比，4.538；95%置信区间，1.756-11.728）、膜 Na+/H+交换调节因子 1 表达阴性（优势比，7.686；95%置信区间，1.876-31.483）和核乳腺癌易感基因 1 阳性（优势比，0.3982；95%置信区间，0.169-0.936）的“新生物标志物”与乳腺癌家族史显著相关。我们假设，人表皮生长因子受体 2、Na+/H+交换调节因子 1 和乳腺癌易感基因 1 的评估可用于临床识别家族性乳腺癌肿瘤，并选择候选乳腺癌易感基因 1/2 基因测序的患者。
