Molecular genetic analysis of surveillance biopsy samples from Barrett's mucosa--significance of sampling.
Our aim was to determine the spectrum and accumulation of mutations in surveillance biopsies from Barrett's mucosa of individual patients during follow-up. We performed loss of heterozygosity (LOH) analysis of six recently described tumor suppressor genes relevant for the carcinogenesis of Barrett's adenocarcinoma from laser-microdissected, paraffin-embedded biopsy samples of Barrett's mucosa without or with low-grade dysplastic change. 118 biopsy samples from 26 patients were taken during surveillance programs in time intervals ranging between 6 and 51 months. We found no significant increase in LOH events at least in a 51-month interval. In two patients, Barrett's adenocarcinoma was diagnosed 6 months after the first diagnosis of Barrett's mucosa. Six of 26 patients did not show LOH. The remaining patients exhibited a striking variation of LOH patterns and accumulations in biopsy samples during follow-up. From our microsatellite marker panel, we were not able to define a single surrogate marker that could serve as a potential biomarker, indicating an increased risk of progression to Barrett's adenocarcinoma. However, LOH combinations, especially APC/p16(INK4) or APC/p53, deserve attention as putative biomarkers in future studies. Our results raise important questions regarding the biological dynamics of mutations in Barrett's mucosa in addition to the influence of sampling, especially with regard to the number of biopsies taken from Barrett's mucosa.
Werther
Meike
M
Pathologie Nordhessen, Wilhelmshöher Allee 287, 34131 Kassel, Germany.
Saure
Christoph
C
Pahl
René
R
Schorr
Friedrich
F
Rüschoff
Josef
J
Alles
Jens Uwe
JU
Heinmöller
Ernst
E
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000235:genetics* / Q000473:pathology; D001706:Biopsy / Q000379:methods; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004945:Esophagoscopy; D004947:Esophagus / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D016158:Genes, p53; D005858:Germany; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D009154:Mutation; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D015203:Reproducibility of Results; D013997:Time Factors