Down regulation of gastric and intestinal phenotypic expression in Epstein-Barr virus-associated stomach cancers.
We have previously demonstrated the importance of gastric and intestinal phenotypic expression for stomach carcinogenesis. In this study, we focused on Epstein-Barr virus (EBV)-associated stomach cancers, with special attention to Cdx2.



We evaluated the expression of gastric and intestinal phenotypic markers by immunohistochemistry in 35 EBV-positive [EBV (+)] and 75 EBV-negative [EBV (-)] stomach cancers in Colombia. The lesions were divided phenotypically into gastric (G), gastric-and-intestinal mixed (GI), intestinal (I), and null (N) phenotypes. In the EBV (+) cases, the lesions were divided phenotypically into 9 G (25.7%), 1 GI (2.9%), 3 I (8.6%), and 22 N (62.9%) types. Similarly, the EBV (-) lesions were also classified phenotypically as 15 G (20.0%), 19 GI (25.3%), 24 I (32.0%), and 17 N (22.7%) types. The proportion of N type EBV (+) lesions was higher than for their EBV (-) counterparts (P<0.0001). The expression of Cdx2 and MUC2 was also found to be significantly lower in EBV (+) than in EBV (-) stomach cancers (P=0.0001; P<0.0001). Cdx2 expression in the intestinal metaplastic glands present in non-neoplastic mucosa surrounding EBV (+) lesions was also significantly lower than in EBV (-) tumors (P=0.016) despite no evidence of EBV infection.



EBV (+) stomach cancers are characterized by low expression of intestinal phenotype markers, including Cdx2, and only occasional gastric phenotypic expression.
Hirano
N
N
Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Tsukamoto
T
T
Mizoshita
T
T
Koriyama
C
C
Akiba
S
S
Campos
F
F
Carrasquilla
G
G
Carrascal
E
E
Cao
X
X
Toyoda
T
T
Ban
H
H
Miki
K
K
Tatematsu
M
M
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D000071616:CDX2 Transcription Factor; D015536:Down-Regulation; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000378:metabolism*; D005260:Female; D004854:Herpesvirus 4, Human; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D055262:Mucin-2; D009077:Mucins / Q000378:metabolism; D010641:Phenotype; D012367:RNA, Viral / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology*
D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C099537:Epstein-Barr virus encoded RNA 1; D018398:Homeodomain Proteins; C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins; D012367:RNA, Viral