A high frequency of human papilloma virus (HPV) DNA type 16 in biopsies of cervical squamous cell neoplasia of Uygur women

Cervical carcinoma ranks among the most common tumors worldwide and is especially prevalent in the developing world. Strong evidence supports the role of human papillomavirus (HPV) infection in the genesis of these tumors. The authors examined 65 cervical neoplasias from a population of women at particularly high risk for the development of cervical cancer in Western China. HPV DNA analysis consisted of in-situ hybridization (n=65) and polymerase chain reaction (PCR) (n=58) for the detection of HPV types 6, 11, 16, 18, 31, 33, and 35. Both consensus and type-specific primers for HPV types 6, 16, and 18 were used in the PCR studies. Overall, HPV DNA was detected in 76.9% of cases. In-situ hybridization identified HPV DNA in 43.1% of patients. PCR with consensus primers detected HPV DNA in 22.4% of lesions, whereas type-specific primers for the HPV E6 gene demonstrated HPV DNA in 77.6% of cervical tumors. Type-specific PCR was more sensitive than L1 consensus PCR and in-situ hybridization for detection of HPV DNA. Thirty-two (55.2%) cases that were negative by L1 consensus PCR and 21 (32.3%) that were negative by in-situ hybridization were positive by type-specific PCR. Of the 50 cases positive for HPV DNA by one or more of these assays, 94% (n=47) were identified as HPV type 16; 4% (n=2) as HPV 31, 33, or 35; and 2% (n=1) as another, unidentified, HPV type. These data support the role of HPV in the pathogenesis of cervical carcinoma in high-risk women living in Western China. This study represents the first report of HPV analyses in Uygur women with cervical cancer

Abnormal TP53 Predicts Risk of Progression in Patients With Barrett’s Esophagus Regardless of a Diagnosis of Dysplasia

Background and aimsBarrett's esophagus (BE) is the precursor to esophageal adenocarcinoma. A major challenge is identifying the small group with BE who will progress to advanced disease from the many who will not. Assessment of p53 status has promise as a predictive biomarker, but analytic limitations and lack of validation have precluded its use. The aim of this study was to develop a robust criteria for grading abnormal immunohistochemical (IHC) expression of p53 and to test its utility as a biomarker for progression in BE.MethodsCriteria for abnormal IHC of p53 were developed in BE biopsies and validated with sequencing to assess TP53 mutations. The utility of p53 IHC as a biomarker for progression of BE was tested retrospectively in 561 patients with BE with or without known progression. The findings were prospectively validated in a clinical practice setting in 1487 patients with BE.ResultsAbnormal p53 IHC highly correlated with TP53 mutation status (90.6% agreement) and was strongly associated with neoplastic progression in the retrospective cohorts, regardless of histologic diagnosis (P < .001). In the retrospective cohort, abnormal p53 was associated with a hazard ratio of 5.03 (95% confidence interval, 3.88-6.5) and a hazard ratio of 5.27 (95% confidence interval, 3.93-7.07) for patients with exclusively nondysplastic disease before progression. In the prospective validation cohort, p53 IHC predicted progression among nondysplastic BE, indefinite for dysplasia, and low-grade dysplasia (P < .001).Conclusionsp53 IHC identifies patients with BE at higher risk of progression, including in patients without evidence of dysplasia. p53 IHC is inexpensive, easily integrated into routine practice, and should be considered in biopsies from all BE patients without high-grade dysplasia or cancer

Detection of Mutations in Barrett’s Esophagus Before Progression to High-Grade Dysplasia or Adenocarcinoma

Background & aimsBarrett's esophagus (BE) is the greatest risk factor for esophageal adenocarcinoma (EAC), but only a small proportion of patients with BE develop cancer. Biomarkers might be able to identify patients at highest risk of progression. We investigated genomic differences in surveillance biopsies collected from patients whose BE subsequently progressed compared to patients whose disease did not progress.MethodsWe performed a retrospective case-control study of 24 patients with BE that progressed to high-grade dysplasia (HGD, n = 14) or EAC (n = 10). The control group (n = 73, called non-progressors) comprised patients with BE and at least 5 years of total endoscopic biopsy surveillance without progression to HGD or EAC. From each patient, we selected a single tissue sample obtained more than 1 year before progression (cases) or more than 2 years before the end of follow-up (controls). Pathogenic mutations, gene copy numbers, and ploidy were compared between samples from progressors and non-progressors.ResultsTP53 mutations were detected in 46% of samples from progressors and 5% of non-progressors. In this case-control sample set, TP53 mutations in BE tissues increased the adjusted risk of progression 13.8-fold (95% confidence interval, 3.2-61.0) (P < .001). We did not observe significant differences in ploidy or copy-number profile between groups. We identified 147 pathogenic mutations in 57 distinct genes-the average number of pathogenic mutations was higher in samples from progressors (n = 2.5) than non-progressors (n = 1.2) (P < .001). TP53 and other somatic mutations were recurrently detected in samples with limited copy-number changes (aneuploidy).ConclusionsIn genomic analyses of BE tissues from patients with or without later progression to HGD or EAC, we found significantly higher numbers of TP53 mutations in BE from patients with subsequent progression. These mutations were frequently detected before the onset of dysplasia or substantial changes in copy number