Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mod Pathol. 2016 Apr;29(4):330-46. doi: 10.1038/modpathol.2016.38. Epub 2016 Feb 26.
Inflammatory breast cancer is the most aggressive form of breast cancer. Identifying new biomarkers to be used as therapeutic targets is in urgent need. Messenger RNA expression profiling studies have indicated that inflammatory breast cancer is a transcriptionally heterogeneous disease, and specific molecular targets for inflammatory breast cancer have not been well established. We performed microRNA expression profiling in inflammatory breast cancer in comparison with locally advanced noninflammatory breast cancer in this study. Although many microRNAs were differentially expressed between normal breast tissue and tumor tissue, most of them did not show differential expression between inflammatory and noninflammatory tumor samples. However, by microarray analysis, quantitative reverse transcription PCR, and in situ hybridization, we showed that microRNA-205 expression was decreased not only in tumor compared with normal breast tissue, but also in inflammatory breast cancer compared with noninflammatory breast cancer. Lower expression of microRNA-205 correlated with worse distant metastasis-free survival and overall survival in our cohort. A small-scale immunohistochemistry analysis showed coexistence of decreased microRNA-205 expression and decreased E-cadherin expression in some ductal tumors. MicroRNA-205 may serve as a therapeutic target in advanced breast cancer including inflammatory breast cancer.
炎性乳腺癌是最具侵袭性的乳腺癌形式。急需确定新的生物标志物作为治疗靶点。信使 RNA 表达谱研究表明,炎性乳腺癌是一种转录异质性疾病,尚未明确炎性乳腺癌的特定分子靶点。在本研究中,我们对炎性乳腺癌与局部晚期非炎性乳腺癌进行了 microRNA 表达谱分析。虽然正常乳腺组织和肿瘤组织之间有许多 microRNA 表达差异,但大多数 microRNA 在炎性和非炎性肿瘤样本之间没有差异表达。然而,通过微阵列分析、定量逆转录 PCR 和原位杂交,我们表明 microRNA-205 的表达不仅在肿瘤组织中与正常乳腺组织相比降低,而且在炎性乳腺癌与非炎性乳腺癌相比也降低。在我们的队列中,microRNA-205 表达降低与远处无转移生存和总生存不良相关。一项小规模的免疫组织化学分析表明,一些导管肿瘤中存在 microRNA-205 表达降低和 E-钙黏蛋白表达降低共存的现象。microRNA-205 可能成为包括炎性乳腺癌在内的晚期乳腺癌的治疗靶点。