Long-term follow-up study of gastric adenoma; tumor-associated macrophages are associated to carcinoma development in gastric adenoma.
BACKGROUND
Some gastric adenomas may progress to adenocarcinoma in a short time, but others remain as adenoma for a long time.


METHODS
Among 1138 cases diagnosed as adenoma by biopsy at Kure Medical Association Hospital between 1990 and 2010, 51 adenomas were enrolled. Of these, 28 adenomas (group A) were followed for 60 months or longer with no progression to adenocarcinoma within 60 months, and the other 23 adenomas (group B) were upgraded to carcinoma by consecutive biopsies performed within 1 year after the first biopsy. These adenomas were compared clinicopathologically and immunohistochemically.


RESULTS
Macroscopically, the mean size of group B adenomas was significantly larger than that of group A adenomas (18.6 vs. 9.9 mm) at the first biopsy. The frequency of a depressed area in the adenoma was significantly higher in group B than group A. Microscopically none of group A but 7 (30.4%) of 23 group B adenomas showed severe atypia. Each of a highly proliferative gland measured by Ki-67 labeling, cellular atypical grade, gastric phenotype defined by MUC5AC and MUC6 and CD204-positive tumor-associated macrophage (TAM) was a significant risk factor for adenocarcinoma development in gastric adenoma by univariate analysis. Only moderate or severe atypia of adenoma cells and the TAM number in the stroma of adenomas were independent risk factors by multivariate analysis.


CONCLUSIONS
As independent risk factors, cellular atypia may reconfirm the importance of morphological analysis, and the TAM number may indicate the significance of TAM function in gastric adenoma.
Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.|Institute for Clinical Research, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama-cho, Kure, 737-0023, Japan.|Department of Diagnostic Pathology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, Kure, Japan.
Daiki
D
Taniyama
Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan. taniyamak@kure-nh.go.jp.|Institute for Clinical Research, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama-cho, Kure, 737-0023, Japan. taniyamak@kure-nh.go.jp.|Department of Diagnostic Pathology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, Kure, Japan. taniyamak@kure-nh.go.jp.
Kiyomi
http://orcid.org/0000-0001-5836-0285
K
Taniyama
Institute for Clinical Research, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama-cho, Kure, 737-0023, Japan.|Department of Diagnostic Pathology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, Kure, Japan.
Kazuya
K
Kuraoka
Institute for Clinical Research, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama-cho, Kure, 737-0023, Japan.|Department of Diagnostic Pathology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, Kure, Japan.
Junichi
J
Zaitsu
Institute for Clinical Research, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama-cho, Kure, 737-0023, Japan.|Department of Diagnostic Pathology, National Hospital Organization, Kure Medical Center and Chugoku Cancer Center, Kure, Japan.
Akihisa
A
Saito
Department of Surgery, Kure Medical Association Hospital, Kure, Japan.
Hirofumi
H
Nakatsuka
Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
Naoya
N
Sakamoto
Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
Kazuhiro
K
Sentani
Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
Naohide
N
Oue
Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
Wataru
W
Yasui
D000230:Adenocarcinoma / Q000473:pathology*; D000236:Adenoma / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000473:pathology*
Adenoma-carcinoma sequence; Gastric adenoma; Tumor-associated macrophages