正常组织、DCIS 和浸润性乳腺癌中杂合性丢失与表达谱的比较分析。

Comparative analysis of loss of heterozygosity and expression profile in normal tissue, DCIS and invasive breast cancer.

机构信息

Oncogynecologic Center, Department of Obstetrics and Gynecology, Charles University in Prague, First Faculty of Medicine and General University Hospital, Apolinarska 18, Prague 2, Czech Republic.

出版信息

Clin Transl Oncol. 2011 Sep;13(9):652-5. doi: 10.1007/s12094-011-0710-1.

DOI:10.1007/s12094-011-0710-1

PMID:21865136

Abstract

INTRODUCTION

Ductal carcinoma in situ (DCIS) is considered to be related to the development of invasive breast cancer. The aim of molecular biological research of preinvasive breast lesion characteristics and comparison with normal tissues and tissue of invasive tumours is to identify patients at high risk of developing invasive tumour on the basis of already established preinvasive lesions, and thus influence clinical decision-making. The aim of our study was to analyse several key molecules involved in different cellular pathways important for cancer development and progression in different types of breast tissue and to describe similarities and differences between premalignant and malignant lesions.

MATERIAL AND METHODS

Genetic material isolated from both the tumour and healthy tissue was examined by loss of heterozygosity (LOH) analysis and real-time PCR using collagen 2A as a house-keeping gene.

RESULTS

We analysed 65 samples of healthy mammary gland, 25 DCIS and 42 invasive ductal breast cancer samples. We analysed the LOH in three genes: BRCA1, BRCA2 and p53; and the gene expression of the VEGF gene and Bcl-2 gene. LOH in the BRCA1 gene was present in 44.74% of invasive samples and in 8.69% of DCIS (p=0.026); LOH in the BRCA2 gene in 45.0% of invasive samples and in 9.52% of DCIS (p=0.036); LOH in the p53 gene in 32.5% of invasive samples and in 31.82% of DCIS (p=0.97). No LOH was observed in normal tissue samples. VEGF was overexpressed in 14.3% of invasive cancers and in 12.0% of DCIS. Overexpression of Bcl-2 was observed in 11.9% of invasive cancers and in 8.0% of DCIS.

CONCLUSION

We have confirmed that some of the molecular characteristics of DCIS are identical to those of invasive carcinoma. This approach could lead to the identification of molecular markers as indicators for the potential development of DCIS into invasive carcinoma or identification of DCIS subgroups with latent invasion.

摘要

简介

导管原位癌（DCIS）被认为与浸润性乳腺癌的发展有关。对浸润前乳腺癌病变特征的分子生物学研究以及与正常组织和浸润性肿瘤组织的比较，旨在根据已确定的浸润前病变识别出发生浸润性肿瘤的高危患者，从而影响临床决策。我们的研究目的是分析不同类型乳腺组织中涉及不同细胞通路的几个关键分子，描述癌前病变和恶性病变之间的相似性和差异性。

材料与方法

通过杂合性缺失（LOH）分析和以胶原蛋白 2A 为管家基因的实时 PCR 检测，对肿瘤和健康组织中的遗传物质进行检测。

结果

我们分析了 65 例健康乳腺、25 例 DCIS 和 42 例浸润性导管乳腺癌样本。我们分析了三个基因的 LOH：BRCA1、BRCA2 和 p53；以及 VEGF 基因和 Bcl-2 基因的表达。BRCA1 基因的 LOH 在 44.74%的浸润性样本和 8.69%的 DCIS 中存在（p=0.026）；BRCA2 基因的 LOH 在 45.0%的浸润性样本和 9.52%的 DCIS 中存在（p=0.036）；p53 基因的 LOH 在 32.5%的浸润性样本和 31.82%的 DCIS 中存在（p=0.97）。正常组织样本中未观察到 LOH。VEGF 在 14.3%的浸润性癌症和 12.0%的 DCIS 中过度表达。Bcl-2 的过表达在 11.9%的浸润性癌症和 8.0%的 DCIS 中观察到。