Expression And Correlation Of Multiple Tumor-suppressor Genes In Breast Cancers And Their Adjacent Hyperplastic Tissues

Purpose: Breast cancer is one of the most frequently diagnosed lesions in women, and contributes severe harm to them. The incidence of this cancer is going up. Thus, it is very important to diagnose and treat breast cancers in early stages. Breast hyperplasia, especially atypical hyperplasia is closely associated with breast cancer. There are morphologic similarities and epidemic correlation between breast hyperplasia and cancer, which suggests that they have same or similar genetic alterations. According to modern molecular biological theory a series of hereditary changes, especially the activation of oncogenes and the inhibition of tumor-suppressor genes contribute to the development of cancers. So we hypothesize that some of breast hyperplastic diseases have undergone changes of oncogenes and tumor-suppressor genes and that cases with such gene changes have higher potentialities to become breast cancers than those without these changes. Therefore it is of great importance of investigating gene changes in breast hyperplastic tissues for understanding the mechanism of carcinogenesis and diagnosing breast cancers in early stages. In this study we considered breast cancers with adjacent hyperplastic tissues as a model of cancer development and progression, and detected the expression and correlation of multiple tumor-suppressor genes in these tissues to investigate the roles of these genes in development and progression of breast cancers.Methods: 92 samples containing invasive carcinoma, carcinoma in situ, atypical hyperplasia and simple hyperplasia were collected from archive paraffin-embedded blocks with breast cancers. Expression of p53, p63, BRCA1, BRCA2, PTEN and Rb genes were detected using immunohistochemistry SP method. Then the stages when abnormal expression of each gene firstly arose were determined. Finally the correlation of abnormal expression among these tumor-suppressor genes was analyzed by Pearson bivariate correlation.Results: 1. In 70 cases of qualified specimens, 67% (47/70) expressed mutated p53 protein, in which 3.9% (2/70) started from simple hyperplasia, 24.3% (17/70) from atypical hyperplasia, 12.9%(9/70) from ductal carcinoma in situ, and27.1%(19/70) from invasive carcinoma. p63 protein expressed in 23.7%(18/76) of 76 qualified specimens, in which 2.6%(2/76) started from atypical hyperplasia, 5.3%(4/76) from ductal carcinoma in situ, and 15.8%(12/76) from invasive carcinoma. No p63 protein expression was detected in simple hyperplasia. 14.5%(10/69) of 69 qualified specimens showed BRCA1 protein expression lose, in which 2.9%(2/69) started from atypical hyperplasia, 2.9%(2/69) from ductal carcinoma in situ, and 8.7%(6/69) from invasive carcinoma. No BRCA1 expression lose was detected in simple hyperplasia. 28.6%(18/63) of 63 qualified specimens showed BRCA2 protein expression lose, in which 6.3%(4/63) started from atypical hyperplasia, 3.2%(2/63) from ductal carcinoma in situ, and 19.0%(12/63) from invasive carcinoma. No BRCA2 expression lose was detected in simple hyperplasia. 22.0%(13/59) of 59 qualified specimens showed PTEN protein expression lose, in which 5.1%(3/59) started from atypical hyperplasia, 6.8%(4/59) from ductal carcinoma in situ, and 10.2%(6/59) from invasive carcinoma. No PTEN expression lose was detected in simple hyperplasia. 37.5%(21/56) of 56 qualified specimens showed Rb protein expression lose, in which 5.4%(3/56) started from atypical hyperplasia, 14.3%(8/56) from ductal carcinoma in situ, and 17.9%(10/56) from invasive carcinoma. No Rb expression lose was detected in simple hyperplasia. 2. 75%(69/92) of the tested cases showed at least one gene abnormal expression, of which 1.1%(1/92) showed five genes abnormal expressions, 3.3%(3/92) cases showed four genes abnormal expressions, 9.8%(9/92) cases showed three genes abnormal expressions, 28.3%(26/92) cases showed two genes abnormal expressions and 32.6%(30/92) cases showed one gene abnormal expression. Altogether there were 42.4%(39/92) cases which showed at least two genes abnormal expressions. As...