Clinical trial NCT00835341: Methylation of p16 CpG Island And Malignant Transformation of Oral Epithelial Dysplasia
Official title: A Cohort Study on Prediction of Malignant Transformation of Oral Epithelial Dysplasia by p16 Methylation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Oral Epithelial Dysplasia, Mild or Moderate Grade
Keywords: oral epithelial dysplasia
p16 methylation
prognosis
malignant transformation
oral squamous cell carcinoma
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2009-02-03
Enrollment: 93
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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 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

Primary outcomes:
measure: The Number of Participants With Both Clinical and Histological Evidence of Malignant Transformation of Oral Epithelial Dysplasia
timeFrame: from 3 months to 124 months
Secondary outcomes:
measure: Cancer-free Survival Time for Patients With Oral Epithelial Dysplasia
timeFrame: from 3 months to 124 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Oral Medicine, Peking University School and Hospital of Stomatology
Study officials:
affiliation: Beijing Cancer Hospital/ Institue, Peking University School of Oncology
name: Dajun Deng, MD
role: STUDY_DIRECTOR
affiliation: Peking University School of Stomatology
name: Hongwei Liu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Sun Y, Deng D, You WC, Bai H, Zhang L, Zhou J, Shen L, Ma JL, Xie YQ, Li JY. Methylation of p16 CpG islands associated with malignant transformation of gastric dysplasia in a population-based study. Clin Cancer Res. 2004 Aug 1;10(15):5087-93. doi: 10.1158/1078-0432.CCR-03-0622.
citation: Cao J, Zhou J, Gao Y, Gu L, Meng H, Liu H, Deng D. Methylation of p16 CpG island associated with malignant progression of oral epithelial dysplasia: a prospective cohort study. Clin Cancer Res. 2009 Aug 15;15(16):5178-83. doi: 10.1158/1078-0432.CCR-09-0580. Epub 2009 Aug 11.