Methylation and immunoexpression of p16ink4a tumor suppressor gene in primary breast cancer tissue and their quantitative p16ink4a hypermethylation in plasma by real-time PCR

Korean Journal of Pathology

Volumn 46, Issue 6, 2012, Pages 554-561

  Lee, Jae Jun ^a   Ko, Eunkyung ^a   Cho, Junhun ^a   Park, Ha Young ^a   Lee, Jeong Eon ^a   Nam, Seok Jin ^a   Kim, Duk Hwan ^b   Cho, Eun Yoon ^a  

^a Sungkyunkwan University School of Medicine   (South Korea)

^b Samsung Medical Center   (South Korea)

Author keywords

Breast; Immunohistochemistry; Methylation; Neoplasms; P16

Indexed keywords

EID: 84874091851     PISSN: 17381843     EISSN: None     Source Type: Journal    
DOI: 10.4132/KoreanJPathol.2012.46.6.554     Document Type: Article

References (30)

1. Kamb A, Gruis NA, Weaver-Feldhaus J, et al. A cell cycle regulator potentially involved in genesis of many tumor types. Science 1994; 264: 436-40.
2. Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 1993; 366: 704-7.
3. Herman JG, Merlo A, Mao L, et al. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res 1995; 55: 4525-30.
4. Di Vinci A, Perdelli L, Banelli B, et al. p16(INK4a) promoter methylation and protein expression in breast fibroadenoma and carcinoma. Int J Cancer 2005; 114: 414-21.
5. Emig R, Magener A, Ehemann V, et al. Aberrant cytoplasmic expression of the p16 protein in breast cancer is associated with accelerated tumour proliferation. Br J Cancer 1998; 78: 1661-8.
6. Han S, Ahn SH, Park K, et al. P16INK4a protein expression is associated with poor survival of the breast cancer patients after CMF chemotherapy. Breast Cancer Res Treat 2001; 70: 205-12.
7. Milde-Langosch K, Bamberger AM, Methner C, Rieck G, Löning T. Expression of cell cycle-regulatory proteins rb, p16/MTS1, p27/KIP1, p21/WAF1, cyclin D1 and cyclin E in breast cancer: correlations with expression of activating protein-1 family members. Int J Cancer 2000; 87: 468-72.
8. Kersting M, Friedl C, Kraus A, Behn M, Pankow W, Schuermann M. Differential frequencies of p16(INK4a) promoter hypermethylation, p53 mutation, and K-ras mutation in exfoliative material mark the development of lung cancer in symptomatic chronic smokers. J Clin Oncol 2000; 18: 3221-9.
9. Kresty LA, Mallery SR, Knobloch TJ, et al. Alterations of p16(INK4a) and p14(ARF) in patients with severe oral epithelial dysplasia. Cancer Res 2002; 62: 5295-300.
10. Lee JH, Park SJ, Abraham SC, et al. Frequent CpG island methylation in precursor lesions and early gastric adenocarcinomas. Oncogene 2004; 23: 4646-54.
11. Bearzatto A, Conte D, Frattini M, et al. p16(INK4A) hypermethylation detected by fluorescent methylation-specific PCR in plasmas from non-small cell lung cancer. Clin Cancer Res 2002; 8: 3782-7.
12. Hsiung DT, Marsit CJ, Houseman EA, et al. Global DNA methylation level in whole blood as a biomarker in head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 2007; 16: 108-14.
13. Kawakami K, Brabender J, Lord RV, et al. Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. J Natl Cancer Inst 2000; 92: 1805-11.
14. Lee TL, Leung WK, Chan MW, et al. Detection of gene promoter hypermethylation in the tumor and serum of patients with gastric carcinoma. Clin Cancer Res 2002; 8: 1761-6.
15. Sharma G, Mirza S, Prasad CP, Srivastava A, Gupta SD, Ralhan R. Promoter hypermethylation of p16INK4A, p14ARF, cyclinD2 and Slit2 in serum and tumor DNA from breast cancer patients. Life Sci 2007; 80: 1873-81.
16. Zhang YJ, Wu HC, Shen J, et al. Predicting hepatocellular carcinoma by detection of aberrant promoter methylation in serum DNA. Clin Cancer Res 2007; 13: 2378-84.
17. Zitt M, Zitt M, Müller HM. DNA methylation in colorectal cancer: impact on screening and therapy monitoring modalities? Dis Markers 2007; 23: 51-71.
18. Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 1998; 11: 155-68.
19. Fackler MJ, McVeigh M, Mehrotra J, et al. Quantitative multiplex methylation-specific PCR assay for the detection of promoter hypermethylation in multiple genes in breast cancer. Cancer Res 2004; 64: 4442-52.
20. Brenner AJ, Paladugu A, Wang H, Olopade OI, Dreyling MH, Aldaz CM. Preferential loss of expression of p16(INK4a) rather than p19(ARF) in breast cancer. Clin Cancer Res 1996; 2: 1993-8.
21. Hui R, Macmillan RD, Kenny FS, et al. INK4a gene expression and methylation in primary breast cancer: overexpression of p16INK4a messenger RNA is a marker of poor prognosis. Clin Cancer Res 2000; 6: 2777-87.
22. Nielsen NH, Roos G, Emdin SO, Landberg G. Methylation of the p16(Ink4a) tumor suppressor gene 5'-CpG island in breast cancer. Cancer Lett 2001; 163: 59-69.
23. Liu T, Niu Y, Feng Y, et al. Methylation of CpG islands of p16(INK4a) and cyclinD1 overexpression associated with progression of intraductal proliferative lesions of the breast. Hum Pathol 2008; 39: 1637-46.
24. Bachmann IM, Straume O, Akslen LA. Altered expression of cell cycle regulators cyclin D1, p14, p16, CDK4 and Rb in nodular melanomas. Int J Oncol 2004; 25: 1559-65.
25. Khouja MH, Baekelandt M, Nesland JM, Holm R. The clinical importance of Ki-67, p16, p14, and p57 expression in patients with advanced ovarian carcinoma. Int J Gynecol Pathol 2007; 26: 418-25.
26. Saegusa M, Machida BD, Okayasu I. Possible associations among expression of p14(ARF), p16(INK4a), p21(WAF1/CIP1), p27(KIP1), and p53 accumulation and the balance of apoptosis and cell proliferation in ovarian carcinomas. Cancer 2001; 92: 1177-89.
27. Geradts J, Hruban RH, Schutte M, Kern SE, Maynard R. Immunohistochemical p16INK4a analysis of archival tumors with deletion, hypermethylation, or mutation of the CDKN2/MTS1 gene. A comparison of four commercial antibodies. Appl Immunohistochem Mol Morphol 2000; 8: 71-9.
28. Dublin EA, Patel NK, Gillett CE, Smith P, Peters G, Barnes DM. Retinoblastoma and p16 proteins in mammary carcinoma: their relationship to cyclin D1 and histopathological parameters. Int J Cancer 1998; 79: 71-5.
29. Geradts J, Wilson PA. High frequency of aberrant p16(INK4A) expression in human breast cancer. Am J Pathol 1996; 149: 15-20.
30. Leong WF, Chau JF, Li B. p53 Deficiency leads to compensatory up-regulation of p16INK4a. Mol Cancer Res 2009; 7: 354-60.