Methylation and Immunoexpression of p16INK4a Tumor Suppressor Gene in Primary Breast Cancer Tissue and Their Quantitative p16INK4a Hypermethylation in Plasma by Real-Time PCR
이재준, 고은경, 조준훈, 박하영, 이정언, 남석진, 김덕환, 조은윤,
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이재준 ( Lee Jae-Jun )
Sungkyunkwan University School of Medicine Samsung Medical Center Department of Pathology
고은경 ( Ko Eun-Kyung )
Sungkyunkwan University School of Medicine Samsung Medical Center Department of Surgery
조준훈 ( Cho Jun-Hun )
Sungkyunkwan University School of Medicine Samsung Medical Center Department of Pathology
박하영 ( Park Ha-Young )
Sungkyunkwan University School of Medicine Samsung Medical Center Department of Pathology
이정언 ( Lee Jeong-Eon )
Sungkyunkwan University School of Medicine Samsung Medical Center Department of Surgery
남석진 ( Nam Seok-Jin )
Sungkyunkwan University School of Medicine Samsung Medical Center Department of Surgery
김덕환 ( Kim Duk-Hwan )
Samsung Biomedical Research Institute Center for Genome Research
조은윤 ( Cho Eun-Yoon )
Sungkyunkwan University School of Medicine Samsung Medical Center Department of Pathology
KMID : 0357920120460060554
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.
키워드
Breast; Neoplasms; p16; Methylation; Immunohistochemistry
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