Detection of human papillomavirus DNA and p53 gene mutations in esophageal cancer samples and adjacent normal mucosa.
OBJECTIVE
There is evidence of a possible etiological role of human papillomaviruses (HPVs) in the development of esophageal tumors. Loss of function of the wild-type p53 tumor suppressor gene product by binding to E6 oncoproteins of high-risk HPVs is considered an important event in tumor development. The aim of this study was to verify the prevalence of HPV infection and p53 mutation in esophageal tumor tissue samples and in the adjacent normal mucosa in patients from a high-risk area in Italy.


METHODS
DNA from 33 biopsy specimens (17 tumor sample biopsies and 16 samples of adjacent normal mucosa) was screened for HPV DNA using two polymerase chain reaction based procedures. Restriction fragment length polymorphism analysis was used for typing. Screening of p53 mutations was performed with polymerase chain reaction-single strand conformation polymorphism analysis and DNA sequencing.


RESULTS
Overall, 8 of 17 patients presented HPV DNA; HPV 16 was detected in 4 of 8 samples. Samples from tumors and adjacent mucosa were positive for mucosal HPVs in 7 of 17 and 4 of 16 cases, respectively. In 1 case, HPV DNA was detected in the normal mucosa only. None of the samples contained HPVs of the epidermodysplasia verruciformis or cutaneous groups. Mutations of p53 were detected in two HPV DNA negative samples. In both cases, the mutation was present in the tumor only.


CONCLUSIONS
Our results are in favor of the involvement of both aberrant p53 expression and HPV infection in the development of esophageal tumors. The high HPV infection rate in patients from a high-risk region suggests that subjects harboring HPVs (in particular HPV 16) in the esophagus should be considered at risk of esophageal malignancies.
Astori
G
G
Institute of Microbiology, Medical Faculty, University of Udine, Udine, Italy. guiseppe.astori@dpmsc.uniud.it
Merluzzi
S
S
Arzese
A
A
Brosolo
P
P
de Pretis
G
G
Maieron
R
R
Pipan
C
C
Botta
G A
GA
D000230:Adenocarcinoma / Q000235:genetics / Q000821:virology*; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000821:virology*; D005260:Female; D005753:Gastric Mucosa / Q000821:virology; D016158:Genes, p53; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
D004279:DNA, Viral