Agosto-Arroyo Emmanuel, Isayeva Tatyana, Wei Shi, Almeida Jonas S, Harada Shuko
Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL.
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL.
Cancer Control. 2017 Jan;24(1):102-110. doi: 10.1177/107327481702400117.
The molecular signature of ductal carcinoma in situ (DCIS) in the breast is not well understood. Erb-b2 receptor tyrosine kinase 2 (ERBB2 [formerly known as HER2/neu]) positivity in DCIS is predictive of coexistent early invasive breast carcinoma. The aim of this study is to identify the gene-expression signature profiles of estrogen receptor (ER)/progesterone receptor (PR)-positive, ERBB2, and triple-negative subtypes of DCIS.
Based on ER, PR, and ERBB2 status, a total of 18 high nuclear grade DCIS cases with no evidence of invasive breast carcinoma were selected along with 6 non-neoplastic controls. The 3 study groups were defined as ER/PR-positive, ERBB2, and triple-negative subtypes.
A total of 49 genes were differentially expressed in the ERBB2 subtype compared with the ER/PR-positive and triple-negative groups. PROM1 was overexpressed in the ERBB2 subtype compared with ER/PR-positive and triple-negative subtypes. Other genes differentially expressed included TAOK1, AREG, AGR3, PEG10, and MMP9.
Our study identified unique gene signatures in ERBB2-positive DCIS, which may be associated with the development of invasive breast carcinoma. The results may enhance our understanding of the progression of breast cancer and become the basis for developing new predictive biomarkers and therapeutic targets for DCIS.
乳腺导管原位癌(DCIS)的分子特征尚未完全明确。DCIS中erb-b2受体酪氨酸激酶2(ERBB2[原称HER2/neu])阳性可预测并存的早期浸润性乳腺癌。本研究旨在确定雌激素受体(ER)/孕激素受体(PR)阳性、ERBB2以及三阴性亚型DCIS的基因表达特征谱。
根据ER、PR和ERBB2状态,选取18例无浸润性乳腺癌证据的高核级DCIS病例以及6例非肿瘤对照。3个研究组分别定义为ER/PR阳性、ERBB2和三阴性亚型。
与ER/PR阳性组和三阴性组相比,ERBB2亚型共有49个基因差异表达。与ER/PR阳性和三阴性亚型相比,PROM1在ERBB2亚型中过表达。其他差异表达的基因包括TAOK1、AREG、AGR3、PEG10和MMP9。
我们的研究在ERBB2阳性DCIS中鉴定出独特的基因特征,这可能与浸润性乳腺癌的发生有关。这些结果可能会加深我们对乳腺癌进展的理解,并成为开发DCIS新的预测生物标志物和治疗靶点的基础。