Methylation of p16INK4a Is a Non-Rare Event in Cervical Intraepithelial Neoplasia

Kang, Suki; Kim, Jungsik; Kim, Hong Bae; Shim, Jung Weon; Nam, Eunji; Kim, Sung Hoon; Ahn, Hee Jung; Choi, Yoon Young; Ding, Boxiao; Song, Keun Jeong; Cho, Nam Hoon

doi:10.1097/00019606-200606000-00003

Cited by 29 publications

(25 citation statements)

References 31 publications

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“…MSP is simple, highly sensitive (1 methylated allele in the presence of 10 5 unmethylated alleles) and non-quantitative test. A minimal degree of methylation can be registered as "positive methylation" depending on the original DNA concentration, primer sets and the number of cycles used for PCR [32,33]. Indeed in different populationsof patients the p16 INK4a methylation was determined in 25-57% of invasive cervical squamous cell carcinomas (I-IV FIGO stages) by MSP [22][23][24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4ain HPV-positive cervical carcinomas

Ivanova

Golovina²,

Завалишина

et al. 2007

BMC Cancer

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Background: High risk type human papilloma viruses (HR-HPV) induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16 ink4a drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16 ink4a overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25-57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16 ink4a overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas

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Section: Discussionmentioning

confidence: 99%

Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4ain HPV-positive cervical carcinomas

Ivanova

Golovina²,

Завалишина

et al. 2007

BMC Cancer

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“…p16INK4A or p16 is a well-established surrogate biomarker of HPV infection in the cervical epithelium and is known to be overexpressed in cervical intraepithelial neoplasia and squamous cell carcinoma [9][10][11][12]. The protein p16 is integral to pRb (retinoblastoma) mediated control of the G1-S phase transition of the cell cycle.…”

Section: Introductionmentioning

confidence: 99%

Tissue transglutaminase 2 as a biomarker of cervical intraepithelial neoplasia (CIN) and its relationship to p16INK4A and nuclear factor κB expression

et al. 2009

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Tissue transglutaminase 2 (TG2) is a recently identified molecule with multifunctional physiological roles. This is the first report of the expression of TG2 in cervical intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma (SCC). For comparison, the expression of p16, a known surrogate biomarker of HPV infection, was evaluated. The expression of nuclear factor kappa B (NF-kappaB), a molecule crucial to inflammation and neoplasia, was also determined to explore its possible linkage with TG2 expression. Twenty cases each with normal cervical histology, CIN1, CIN2, CIN3, and invasive SCC were analyzed for TG2, p16, and NF-kappaB expression by immunohistochemistry. Intergroup differences were analyzed by Friedman ANOVA. Cytoplasmic as well as nuclear TG2 expression was observed in the epithelial cells. As compared to normal controls, CIN1 showed markedly increased cytoplasmic TG2 expression (p = 0.006). In CIN2/3, additional nuclear TG2 expression was seen (p = 0.009 and 0.031, respectively). Marked extracellular stromal upregulation of TG2 was noted in CIN3/SCC versus normal controls (p = 0.054; p = 0.003). There was no relationship of TG2 with either p16 of NF-kappaB expression. Combining TG2 immunoreactivity with p16 increased the immunolabeling of dysplasia from 35% to 100% in CIN1, 45% to 60% in CIN2, and 60% to 85% in CIN3. TG2 serves as an additional biomarker for all grades of cervical dysplasia, especially for low-grade dysplasia.

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“…Indeed, MSP is a simple, highly sensitive and nonquantitative test. A minimal degree of methylation can be registered as "positive methylation" depending on the original DNA concentration, primer sets, and the number of cycles used for PCR (46,47).…”

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confidence: 99%

Status of p16<SUP>INK4a</SUP> and E-Cadherin Gene Promoter Methylation in Moroccan Patients With Cervical Carcinoma

Attaleb¹,

W²,

Khyatti³

et al. 2009

oncol res

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Aberrant methylation of tumor suppressor gene promoters has been extensively investigated in cervical cancer. Transcriptional silencing, as a main consequence of hypermethylation of CpG islands, is the predominant mechanism of p16 INK4a and E-cadherin gene inactivation in malignant epithelial tumors. This study was conducted to evaluate the promoter methylation status of p16 INK4a and E-cadherin genes in 22 specimens of cervical carcinomas, four cervical cancer cell lines (HeLa, SiHa, Caski, C33A), and 20 human papillomavirus negative specimens, obtained from normal cervical swabs, using the methylation-specific PCR approach. Hypermethylation of the 5′ CpG island of the p16 INK4a and E-cadherin genes were found in 13 (59.1%) and 10 (45.5%) of 22 cervical cancer samples, respectively. Furthermore, our findings did not show any correlation between promoter methylation of p16 INK4a and E-cadherin genes and clinicopathological parameters, including HPV infection, phenotypic distribution, and stage of the disease. However, hypermethylation of E-cadherin gene promoter appears to be age related in cervical cancer, whereas the frequency of aberrant methylation of p16 INK4a gene promoter is unchanged according to the age of patients. Thus, caution must be made to use these markers in the diagnosis of cervical cancer. However, dietary or pharmaceutical agents that can inhibit these epigenetic events may prevent or delay the development of cervical cancer.

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Methylation of p16INK4a Is a Non-Rare Event in Cervical Intraepithelial Neoplasia

Cited by 29 publications

References 31 publications

Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4ain HPV-positive cervical carcinomas

Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4ain HPV-positive cervical carcinomas

Tissue transglutaminase 2 as a biomarker of cervical intraepithelial neoplasia (CIN) and its relationship to p16INK4A and nuclear factor κB expression

Status of p16<SUP>INK4a</SUP> and E-Cadherin Gene Promoter Methylation in Moroccan Patients With Cervical Carcinoma

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