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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00835341
Recruitment Status : Completed
First Posted : February 3, 2009
Results First Posted : February 23, 2010
Last Update Posted : June 1, 2015
Information provided by (Responsible Party):
Dajun Deng, Peking University

Brief Summary:
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.

Condition or disease
Oral Epithelial Dysplasia, Mild or Moderate Grade

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.

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Study Type : Observational
Actual Enrollment : 93 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Cohort Study on Prediction of Malignant Transformation of Oral Epithelial Dysplasia by p16 Methylation
Study Start Date : March 2005
Actual Primary Completion Date : October 2008
Actual Study Completion Date : October 2008

Resource links provided by the National Library of Medicine

patients with mild or moderate oral epithelial dysplasia containing methylated p16 CpG island.
patients with mild or moderate oral epithelial dysplasia NOT containing methylated p16 CpG island.

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Cancer-free Survival Time for Patients With Oral Epithelial Dysplasia [ Time Frame: from 3 months to 124 months ]

Biospecimen Retention:   Samples With DNA
Tissue specimen are collected from outpatients and inpatients with oral leukoplakia by biopsy or surgical resection, fixed in neutral buffered formalin, and embedded in paraffin. Genomic DNA is extracted from tissue sections.

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00835341

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

Additional Information:
Publications of Results:
Other Publications:
Gale N, Westra W, Pilch BZ, et al. Epithelial precursors lesions. In: Barnes L, Eveson JW, Reichart P, et al. eds. World Health Organization Classification of Tumors: Pathology and Genetics of Head and Neck Tumors. IARC Press, Lyon (France); 2005: 177-179.

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Responsible Party: Dajun Deng, Professor and Department Director, Peking University Identifier: NCT00835341     History of Changes
Other Study ID Numbers: CPDHS-434
First Posted: February 3, 2009    Key Record Dates
Results First Posted: February 23, 2010
Last Update Posted: June 1, 2015
Last Verified: May 2015
Keywords provided by Dajun Deng, Peking University:
oral epithelial dysplasia
p16 methylation
malignant transformation
oral squamous cell carcinoma
Additional relevant MeSH terms:
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Carcinoma in Situ
Pathologic Processes
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type