Gupta Vivek, Agarwal Prerna, Deshpande Prajakta
Department of Pathology & In-charge, Molecular Diagnostics and Research Laboratory, Government Institute of Medical Sciences, India.
Department of Physiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Wardha, India.
Ann Diagn Pathol. 2021 Jun;52:151722. doi: 10.1016/j.anndiagpath.2021.151722. Epub 2021 Feb 11.
Breast cancer is the most common malignancy in women caused by genetic and epigenetic changes. Promoter DNA methylation in tumor suppressor gene plays a major role in breast cancer. The study determined the association of promoter DNA methylation of RASSF1A gene with clinicopathological features in tumor and non-tumor tissue.
A cross sectional study was conducted in the Department of Pathology, Government Institute of Medical Sciences, Greater Noida and Molecular Pathology Laboratory, Department of Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences. Two sections, one from tumor and the other from non-tumor tissue, were obtained and processed for DNA extraction and bisulphite conversion. Methylation specific PCR was done and results of RASSF1A promoter methylation were statistically correlated with clinicopathological features.
Of the 27 breast cancer tissue, 22 showed invasive ductal carcinoma, one showed invasive lobular carcinoma, another showed ductal carcinoma in situ and three cases showed malignant phyllodes tumor of breast. DNA promoter methylation was found in all the cases. 93% of tumor tissue samples and 67% of the non-tumor tissue samples were found to be aberrantly methylated. Tumor size and histological grade were found to be significantly (p-val <0.05) associated with the RASSF1A gene promoter methylation.
A significant association of higher tumor size and tumor histological grade with promoter methylation of RASSF1A gene exists suggestive of its being an important determinant of prognostic staging. This critical event in tumorigenesis may be of clinical utility in assessing breast cancer progression.
The study focuses on the RASSF1A gene promoter methylation and its impact on the clinicopathological features in Indian breast cancer patients highlighting the differences from other genetically different population. We found that RASFF1A gene methylation has significant impact on tumor size and tumor grade. The work carries high significance because it addresses the DNA methylation of tumor suppressor gene in relevance of breast cancer. It may also be the first such report on Indian patients with breast cancer.
乳腺癌是女性中最常见的恶性肿瘤，由基因和表观遗传变化引起。肿瘤抑制基因启动子DNA甲基化在乳腺癌中起主要作用。本研究确定了RASSF1A基因启动子DNA甲基化与肿瘤及非肿瘤组织临床病理特征之间的关联。
在大诺伊达政府医学科学研究所病理科和贾瓦哈拉尔尼赫鲁医学院达塔梅格医学科学研究所病理科分子病理实验室进行了一项横断面研究。获取肿瘤组织和非肿瘤组织各两个切片，进行DNA提取和亚硫酸氢盐转化处理。进行甲基化特异性PCR，并将RASSF1A启动子甲基化结果与临床病理特征进行统计学关联分析。
27例乳腺癌组织中，22例为浸润性导管癌，1例为浸润性小叶癌，1例为导管原位癌，3例为乳腺恶性叶状肿瘤。所有病例均发现DNA启动子甲基化。93%的肿瘤组织样本和67%的非肿瘤组织样本存在异常甲基化。发现肿瘤大小和组织学分级与RASSF1A基因启动子甲基化显著相关（p值<0.05）。
肿瘤大小和肿瘤组织学分级与RASSF1A基因启动子甲基化存在显著关联，提示其为预后分期的重要决定因素。肿瘤发生过程中的这一关键事件可能在评估乳腺癌进展方面具有临床应用价值。
本研究聚焦于RASSF1A基因启动子甲基化及其对印度乳腺癌患者临床病理特征的影响，突出了与其他基因不同人群的差异。我们发现RASFF1A基因甲基化对肿瘤大小和肿瘤分级有显著影响。这项工作具有重要意义，因为它涉及与乳腺癌相关的肿瘤抑制基因的DNA甲基化。这也可能是关于印度乳腺癌患者的首份此类报告。
