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

This study has been completed.
Sponsor:
Information provided by:
Peking University
ClinicalTrials.gov Identifier:
NCT00835341
First received: February 2, 2009
Last updated: February 1, 2010
Last verified: November 2009
  Purpose

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
Oral Epithelial Dysplasia, Mild or Moderate Grade

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Cohort Study on Prediction of Malignant Transformation of Oral Epithelial Dysplasia by p16 Methylation

Resource links provided by NLM:


Further study details as provided by Peking University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cancer-free Survival Time for Patients With Oral Epithelial Dysplasia [ Time Frame: from 3 months to 124 months ] [ Designated as safety issue: No ]

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.


Enrollment: 93
Study Start Date: March 2005
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.

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.
  Eligibility

Genders Eligible for Study:   Both
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.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00835341

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

Additional Information:
Publications:
Responsible Party: Dajun Deng, Professor, Peking University School of Oncology
ClinicalTrials.gov Identifier: NCT00835341     History of Changes
Other Study ID Numbers: CPDHS-434
Study First Received: February 2, 2009
Results First Received: October 21, 2009
Last Updated: February 1, 2010
Health Authority: China: Ethics Committee

Keywords provided by Peking University:
oral epithelial dysplasia
p16 methylation
prognosis
malignant transformation
oral squamous cell carcinoma

Additional relevant MeSH terms:
Carcinoma in Situ
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on August 26, 2014