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1 "Duk-Hwan Kim"
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Original Article
Methylation and Immunoexpression of p16INK4a Tumor Suppressor Gene in Primary Breast Cancer Tissue and Their Quantitative p16INK4a Hypermethylation in Plasma by Real-Time PCR
Jae Jun Lee, Eunkyung Ko, Junhun Cho, Ha Young Park, Jeong Eon Lee, Seok Jin Nam, Duk-Hwan Kim, Eun Yoon Cho
Korean J Pathol. 2012;46(6):554-561.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.554
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  • 17 Crossref
AbstractAbstract PDF
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.

Citations

Citations to this article as recorded by  
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    Cellular and Molecular Life Sciences.2020; 77(4): 559.     CrossRef
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  • p16INK4a overexpression as a predictor of survival in ocular surface squamous neoplasia
    Sheetal Chauhan, Seema Sen, Anjana Sharma, Seema Kashyap, Radhika Tandon, Mandeep S Bajaj, Neelam Pushker, Murugesan Vanathi, Shyam S Chauhan
    British Journal of Ophthalmology.2018; 102(6): 840.     CrossRef
  • Liquid biopsy prediction of axillary lymph node metastasis, cancer recurrence, and patient survival in breast cancer
    Ju-Han Lee, Hoiseon Jeong, Jung-Woo Choi, Hwa Eun Oh, Young-Sik Kim
    Medicine.2018; 97(42): e12862.     CrossRef
  • EZH2 inhibition sensitizes tamoxifen‑resistant breast cancer cells through cell cycle regulation
    Si Chen, Fan Yao, Qinghuan Xiao, Qiannan Liu, Yikun Yang, Xuejuan Li, Guanglie Jiang, Takayoshi Kuno, Yue Fang
    Molecular Medicine Reports.2017;[Epub]     CrossRef
  • Aberrant promoter methylation of cancer-related genes in human breast cancer
    Liang Wu, Ye Shen, Xianzhen Peng, Simin Zhang, Ming Wang, Guisheng Xu, Xianzhi Zheng, Jianming Wang, Cheng Lu
    Oncology Letters.2016; 12(6): 5145.     CrossRef
  • Centrosome aberrations in human mammary epithelial cells driven by cooperative interactions between p16INK4a deficiency and telomere-dependent genotoxic stress
    Daniel Domínguez, Purificación Feijoo, Aina Bernal, Amaia Ercilla, Neus Agell, Anna Genescà, Laura Tusell
    Oncotarget.2015; 6(29): 28238.     CrossRef
  • Relationships Betweenp16Gene Promoter Methylation and Clinicopathologic Features of Colorectal Cancer: A Meta-Analysis of 27 Cohort Studies
    Yan-Zhi Chen, Dan Liu, Yu-Xia Zhao, He-Tong Wang, Ya Gao, Ying Chen
    DNA and Cell Biology.2014; 33(10): 729.     CrossRef
  • Endocrine disruption of the epigenome: a breast cancer link
    Kevin C Knower, Sarah Q To, Yuet-Kin Leung, Shuk-Mei Ho, Colin D Clyne
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    General Thoracic and Cardiovascular Surgery.2014; 62(11): 678.     CrossRef
  • Limoniastrum guyonianum aqueous gall extract induces apoptosis in human cervical cancer cells involving p16INK4A re-expression related to UHRF1 and DNMT1 down-regulation
    Mounira Krifa, Mahmoud Alhosin, Christian D Muller, Jean-Pierre Gies, Leila Chekir-Ghedira, Kamel Ghedira, Yves Mély, Christian Bronner, Marc Mousli
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  • Diagnostic and prognostic value of circulating tumor-related DNA in cancer patients
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    Expert Review of Molecular Diagnostics.2013; 13(8): 827.     CrossRef
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J Pathol Transl Med : Journal of Pathology and Translational Medicine