Methylation of p16 CpG Island And Malignant Transformation of Oral Epithelial Dysplasia

May 7, 2015 updated by: Dajun Deng, Peking University

A Cohort Study on Prediction of Malignant Transformation of Oral Epithelial Dysplasia by p16 Methylation

Oral epithelial dysplasia (OED) is one of the common precancerous lesions among Chinese adults. Biomarker is not available for detection of malignant potential of OED till now. p16 is an important tumor suppressor gene, which is inactivated frequently by methylation of CpG island in early stage of carcinogenesis. The present cohort study is to investigate whether p16 methylation is correlated with malignant transformation of OED.

Study Overview

Status

Completed

Conditions

Detailed Description

  • Background: Identification of malignant potential of oral epithelial dysplasia (OED) is virtually impossible on histopathological grounds alone. Inactivation of p16 gene by CpG methylation is an early frequent event during oral carcinogenesis. To investigate the predictive value of p16 methylation on malignant potential in OED, we carried out the prospective cohort study.
  • Methods: 101 patients with histologically confirmed mild or moderate OED were included in the present study. Baseline information of p16 methylation status of the OED lesions from 93 cases was obtained by methylation-specific PCR. Progression of the OEDs lesions was examined in 78 cases histologically during the 45.8 months double-blind followup survey (78/93). The association between p16 methylation and progression of OED was analyzed with SPSS13.0 software. All P-values were two-sided.

Study Type

Observational

Enrollment (Actual)

93

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 100081
        • Department of Oral Medicine, Peking University School and Hospital of Stomatology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

101 patients with mild or moderate OED were selected from cases with oral leukoplakia, lichen planus, or chronic discoid erythematosus at Peking University School of Stomatology between 1995 and 2005. All of the patients with OED had been diagnosed pathologically by at least two senior pathologists using the criteria from '2005 WHO Classification System' (Gale et al, 2005). All cases involved primary lesions without any LASER, radiation therapy or chemotherapy. p16 methylation status of OED samples was analyzed with methylation-specific PCR combined with denatured high performance liquid chromatography (Sun et al, 2004). 93 eligible cases with p16-methylated or p16-unmethylated OED were enrolled into the cohort study.

Description

Inclusion Criteria:

  • histological diagnosis of mild or moderate grade OED; and
  • enough amount of tissue sample from OED lesion for genomic DNA extraction; and
  • available of methylation status of p16 CpG island in the extracted DNA sample.

Exclusion Criteria:

  • histological diagnosis of severe grade OED or malignant disease; or
  • amount of tissue sample is not enough for preparation of genomic DNA (20ng); or
  • quality of the prepared DNA is not good enough for detection of p16 methylation; or
  • OED treatment history by LASER, radiotherapy, or chemotherapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
p16-methylated
patients with mild or moderate oral epithelial dysplasia containing methylated p16 CpG island.
p16-unmethylated
patients with mild or moderate oral epithelial dysplasia NOT containing methylated p16 CpG island.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Number of Participants With Both Clinical and Histological Evidence of Malignant Transformation of Oral Epithelial Dysplasia
Time Frame: from 3 months to 124 months
The follow-up examination was carried out with a 3-month interval. Re-biopsy was done as clinically indicated, e.g. the lesion recurs or has tendency for malignant development. Pathologic diagnosis was made by at least two pathologists without the knowledge of baseline p16 methylation, based on the World Health Organization's criteria, at Peking University School of Stomatology. The number of participants with malignant transformation of oral dysplasia was calculated based on the number of participants with oral dysplasia progressed to carcinoma by the end of the trial in each cohorts.
from 3 months to 124 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Cancer-free Survival Time for Patients With Oral Epithelial Dysplasia
Time Frame: from 3 months to 124 months
from 3 months to 124 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University

Investigators

  • Study Director: Dajun Deng, MD, Beijing Cancer Hospital/ Institue, Peking University School of Oncology
  • Principal Investigator: Hongwei Liu, MD, PhD, Peking University School of Stomatology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2005

Primary Completion (ACTUAL)

October 1, 2008

Study Completion (ACTUAL)

October 1, 2008

Study Registration Dates

First Submitted

February 2, 2009

First Submitted That Met QC Criteria

February 2, 2009

First Posted (ESTIMATE)

February 3, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

June 1, 2015

Last Update Submitted That Met QC Criteria

May 7, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CPDHS-434

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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