FOXA1 expression in breast cancer - Correlation with luminal subtype A and survival
FOXA1 expression in breast cancer - Correlation with luminal subtype A and survival
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DOI：
10.1158/1078-0432.ccr-07-0122
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发表时间：
2007-08-01
影响因子：
11.5
通讯作者：
Nakshatri, Harikrishna
中科院分区：
文献类型：
--
作者：
Badve, Sunil;Turbin, Dmitry;Nakshatri, Harikrishna
用途：FOXA 1是一种叉头家族转录因子，对接近50%的雌激素受体α（ER α）：雌激素应答基因的最佳表达至关重要。FOXA 1在乳腺癌细胞中表达。在DNA微阵列分析中，它与表征管腔亚型的基因分离。FOXA 1作为一个可能的独立的预后因素的效用尚未确定在乳腺cancer.Materials和方法：组织微阵列，包括438例患者的肿瘤与15.4年中位随访FOXA 1表达免疫组化进行了分析。沿着其他预后因素如肿瘤分级、大小、淋巴结状态、ER、孕激素受体（PR）和HER 2/neu，分析了404例患者中获得的可解释FOXA 1表达。404例乳腺癌中有300例FOXA 1表达（评分3），且FOXA 1表达与ER相关PR（P = 0.00001）和管腔A亚型（P = 0.000001）。随着肿瘤分级的恶化，观察到表达缺失（P = 0.001）。单变量分析显示，淋巴结状态（P = 0.0000012）、肿瘤大小（P = 0.00001）、FOXA 1（P = 0.0004）和ER（P = 0.012）是乳腺癌特异性生存的预测因子。多因素分析显示，只有淋巴结状态（P = 0.001）和肿瘤大小（P = 0.039）是重要的预后因素，而FOXA 1（P = 0.060）和ER（P = 0.131）没有意义。在管腔亚型A患者亚组中，FOXA 1表达与更好的癌症特异性生存相关在ER阳性的亚组中，ER表达水平是预测肿瘤特异性生存率的较好指标（P = 0.009）比PR（P = 0.213）。FOXA 1表达与管腔型A乳腺癌相关，是ER阴性乳腺癌患者癌症特异性生存期的重要预测因子。阳性肿瘤FOXA 1在这些低风险乳腺癌中的预后能力可能被证明在临床治疗决策中是有用的。
Purpose: FOXA1, a forkhead family transcription factor, is essential for optimum expression of similar to 50% of estrogen receptor a (ER alpha):estrogen responsive genes. FOXA1 is expressed in breast cancer cells. It segregates with genes that characterize the luminal subtypes in DNA microarray analyses. The utility of FOXA1 as a possible independent prognostic factor has not been determined in breast cancers.Materials and Methods: A tissue microarray comprising tumors from 438 patients with 15.4 years median follow-up was analyzed for FOXA1 expression by immunohistochemistry. Interpretable FOXA1 expression obtained in 404 patients was analyzed along with other prognostic factors like tumor grade, size, nodal status, ER, progesterone receptor (PR), and HER2/neu.Results: FOXA1 expression (score)3) was seen in 300 of 404 breast cancers and it correlated with ER (P = 0.000001), PR (P = 0.00001), and luminal A subtype (P = 0.000001). Loss of expression was noted with worsening tumor grade (P = 0.001). Univariate analysis showed nodal status (P = 0.0000012), tumor size (P = 0.00001), FOXA1 (P = 0.0004), and ER (P = 0.012) to be predictors of breast cancer-specific survival. Multivariate analysis showed only nodal status (P = 0.001) and tumor size (P = 0.039) to be significant prognostic factors, whereas FOXA1 (P = 0.060) and ER (P = 0.131) were not significant. In luminal subtype A patient subgroup, FOXA1 expression was associated with better cancer-specific survival (P = 0.024) and in ER-positive subgroup, it was better predictor of cancer-specific survival (P = 0.009) than PR (P = 0.213).Conclusion: FOXA1 expression correlates with luminal subtype A breast cancer and it is significant predictor of cancer-specific survival in patients with ER-positive tumors. Prognostic ability of FOXA1 in these low-risk breast cancers may prove to be useful in clinical treatment decisions.