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GATA3 阳性乳腺癌的临床病理分析,特别关注新辅助化疗的反应。

Clinicopathological analysis of GATA3-positive breast cancers with special reference to response to neoadjuvant chemotherapy.

机构信息

Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.

Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.

出版信息

Ann Oncol. 2012 Dec;23(12):3051-3057. doi: 10.1093/annonc/mds120. Epub 2012 Jul 5.

Abstract

BACKGROUND

The aim of this study was to investigate the clinicopathological characteristics of GATA binding protein 3 (GATA3)-positive breast cancers as well as the association of GATA3 expression with response to chemotherapy.

PATIENTS AND METHODS

Tumor specimens obtained before neoadjuvant chemotherapy [paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide)] from breast cancer patients (n = 130) were subjected to immunohistochemical and mutational analysis of GATA3 and DNA microarray gene expression analysis for intrinsic subtyping.

RESULTS

Seventy-four tumors (57%) were immunohistochemically positive for GATA3. GATA3-positive tumors were significantly more likely to be lobular cancer, estrogen receptor (ER)-positive, progesterone receptor (PgR)-positive, Ki67-negative, and luminal A tumors. Somatic mutations were found in only three tumors. Pathological complete response (pCR) was observed in 8 (11%) GATA3-positive tumors and in 22 (39%) GATA3-negative tumors. multivariate analysis showed that tumor size, human epidermal growth factor receptor 2 (her2), and gata3 were independent predictors of pcr.

CONCLUSIONS

GATA3-positive breast cancers showed luminal differentiation characterized by high ER expression and were mostly classified as luminal-type tumors following intrinsic subtyping. Interestingly, GATA3 was an independent predictor of response to chemotherapy, suggesting that GATA3 might be clinically useful as a predictor of a poor response to chemotherapy.

摘要

背景

本研究旨在探讨 GATA 结合蛋白 3(GATA3)阳性乳腺癌的临床病理特征,以及 GATA3 表达与化疗反应的关系。

方法

对接受新辅助化疗[紫杉醇序贯氟尿嘧啶/表柔比星/环磷酰胺]的乳腺癌患者(n=130)的肿瘤标本进行 GATA3 免疫组织化学和突变分析,以及 DNA 微阵列基因表达分析进行内在分型。

结果

74 例肿瘤(57%)免疫组化 GATA3 阳性。GATA3 阳性肿瘤更可能为小叶癌、雌激素受体(ER)阳性、孕激素受体(PgR)阳性、Ki67 阴性和 luminal A 型肿瘤。仅在 3 例肿瘤中发现体细胞突变。8 例(11%)GATA3 阳性肿瘤和 22 例(39%)GATA3 阴性肿瘤观察到病理完全缓解(pCR)。多变量分析显示肿瘤大小、人表皮生长因子受体 2(her2)和 gata3 是 pcr 的独立预测因子。

结论

GATA3 阳性乳腺癌表现出高 ER 表达的 luminal 分化特征,并且在内在分型后大多被归类为 luminal 型肿瘤。有趣的是,GATA3 是化疗反应的独立预测因子,这表明 GATA3 可能在临床上作为化疗反应不良的预测因子有用。

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