Methylation and Immunoexpression of p16INK4a Tumor Suppressor Gene in Primary Breast Cancer Tissue and Their Quantitative p16INK4a Hypermethylation in Plasma by Real-Time PCR.
- Author:
Jae Jun LEE
1
;
Eunkyung KO
;
Junhun CHO
;
Ha Young PARK
;
Jeong Eon LEE
;
Seok Jin NAM
;
Duk Hwan KIM
;
Eun Yoon CHO
Author Information
1. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. eunyoon.cho@samsung.com
- Publication Type:Original Article
- Keywords:
Breast;
Neoplasms;
p16;
Methylation;
Immunohistochemistry
- MeSH:
Breast;
Breast Neoplasms;
Carcinoma, Intraductal, Noninfiltrating;
DNA;
Estrogens;
Genes, p16;
Genes, Tumor Suppressor;
Humans;
Immunohistochemistry;
Methylation;
Plasma;
Polymerase Chain Reaction;
Real-Time Polymerase Chain Reaction;
Receptors, Progesterone
- From:Korean Journal of Pathology
2012;46(6):554-561
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: The p16INK4a gene methylation has been reported to be a major tumorigenic mechanism. METHODS: We evaluated the methylation status of the p16INK4a genes in 231 invasive breast cancer and 90 intraductal carcinoma specimens using a methylation-specific polymerase chain reaction and p16 protein expression using immunohistochemistry. The quantity of cell-free methylated p16INK4a DNA in the plasma samples of 200 patients with invasive breast cancer was also examined using a fluorescence-based real-time polymerase chain reaction assay. RESULTS: The frequencies of p16INK4a methylation in invasive and intraductal tumors were 52.8% (122/231) and 57.8% (52/90), respectively. The p16 protein was overexpressed in 145 of the 231 invasive carcinomas (62.8%) and 63 of the 90 intraductal carcinomas (70%). High p16 expression in invasive carcinomas correlated significantly with a high histologic grade, a negative estrogen receptor and progesterone receptor status, p53 immunoreactivity and high Ki-67 expression with immunohistochemistry. In addition, the methylation index of p16INK4a was significantly higher in the cancer patients than the normal controls (p<0.001). CONCLUSIONS: High p16 immunoreactivity correlated with a loss of differentiation in breast carcinomas and high frequency of p16INK4a promoter methylation in both invasive and intraductal carcinomas, suggesting it may be involved in the pathogenesis of breast cancer.
