Premium
PATHOLOGICAL AND MOLECULAR‐BIOLOGICAL STUDIES ON SEQUENCE FROM REFLUX ESOPHAGITIS TO DEVELOPMENT OF BARRETT's ADENOCARCINOMA
Author(s) -
Wada Ryo,
Yamaguchi Toshikazu,
Tanizaki Takayuki
Publication year - 2005
Publication title -
digestive endoscopy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.5
H-Index - 56
eISSN - 1443-1661
pISSN - 0915-5635
DOI - 10.1111/j.1443-1661.2005.00461.x
Subject(s) - pathology , microdissection , histogenesis , adenocarcinoma , loss of heterozygosity , intestinal metaplasia , microsatellite instability , metaplasia , carcinoma , esophagus , dysplasia , medicine , biopsy , immunohistochemistry , biology , cancer , microsatellite , biochemistry , allele , gene
Background: Barrett's adenocarcinoma is considered to develop via a dysplasia‐carcinoma sequence. However, this theory is thought to be incomplete, because the reports supporting it have been led by an investigation using relatively large‐sized neoplasias or biopsy materials. We think that the minute‐sized neoplasias and the propria mucosa adjacent to these lesions must be examined histologically to clarify the histogenesis of digestive tract carcinoma. In the present study, new findings on the histogenesis of Barrett's adenocarcinoma were revealed according to this point described above. Methods: First, Barrett's epithelium (in particular, specialized colmunar epithelium: SCE) was investigated histologically and immunohistochemically. Second, 28 lesions of the super‐minute tubular neoplasia within 1 mm in maximum diameter in Barrett's esophagus (SMBa) were detected by pathological examinations, and loss of heterozygosity of microsatellite markers (TP53, D17S796 and D17S786) in chromosome 17‐related p53 (p53‐LOH) in these SMBa lesions were examined by DNA extraction using microdissection and high resolution fluorescence labeled PCR primers. Results: Histological and immunohistochemical findings showed that the tubules of SCE had a three‐layer structure and typical SCE should be thought to be the large bowel‐type of the intestinal metaplasia (or goblet cell metaplasia) in the cardiac gland mucosa. According to the overexpression of p53 protein labeling index (p53‐LI), the SMBa lesions were divided into two groups. Three lesions with p53‐LI over 90%, which were thought to be intramucosal adenocarcinoma morphologically, showed high frequency of p53‐LOH (loss of heterozygosity) (100%), and 25 lesions with an average p53‐LI of 58%, which were thought to be benign neoplasia morphologically, also showed p53‐LOH (36%). Conclusions: SCE is thought to be the large bowel type of the intestinal metaplasia in the cardiac gland mucosa. Pathological and molecular‐biological findings of SMBa in SCE supports the dysplasia‐carcinoma sequence in the histogenesis of Barrett's cancer and synchronously some SMBa suggests that there is a different route, the so‐called de novo carcinoma theory.