title: [Clinicopathologic features and protein expression study of Epstein-Barr virus-associated gastric carcinoma in Guangzhou].
abstract: OBJECTIVE
  To investigate the prevalence of Epstein-Barr virus (EBV)-associated gastric carcinomas in Guangzhou, their clinicopathologic features and related protein expressions including DNMT1, p16, and cyclin D1.
  
  
  METHODS
  A total of 676 cases of EBV-associated gastric carcinoma were included in the study. The presence of EBV-encoded small RNA1 (EBER1), a marker for EBV infection, was analyzed by in-situ hybridization using formalin-fixed and paraffin-embedded tumor samples. Expression of EBV-encoded proteins, DNMT1, p16 and cyclin D1 were detected by immunohistochemistry.
  
  
  RESULTS
  Forty-five of 676 gastric carcinomas showed EBER intranuclear positivity in all tumor cells. EBV involvement was significantly more frequent among the male than the female patients, especially in tumors of less differentiated types (diffuse type) and involving the upper stomach (P < 0.05). EBNA1 and LMP2A expression were detected in 42 (93.3%) and 24 (53.3%) cases, respectively. None expressed EBNA2, LMP1, and ZEBRA. Among 45 cases of EBV associated gastric carcinomas, DNMT1, p16 and cyclin D1 expression were seen in 35 (77.8%), 10 (22.2%), and 29 (64.4%) cases, respectively. In contrast, among 40 EBV negative gastric carcinomas, expression of the three proteins were 20 (50.0%), 25 (62.5%) and 12 (30.0%), respectively. The difference of expression of the three proteins between the two groups was significant (P < 0.05). Expression of p16 correlated with the depth of the tumor invasion. Correlated protein expression was seen between LMP2A and DNMT1, between DNMT1 and p16, and between p16 and cyclin D1 (P < 0.05).
  
  
  CONCLUSIONS
  EBV associated gastric carcinoma accounts for 6.7% of gastric carcinomas in Guangzhou with the Latency I pattern in some cases and between Latency I and II in others. The correlated expression of LMP2A, DNMT1, p16 and cyclin D1 may contribute to the pathogenesis of EBV associated gastric carcinomas.
authors.affiliation: Department of Pathology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Han
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Feng
authors.forename: Yun-Gang
authors.initials: YG
authors.lastname: Ding
authors.forename: Chun-Kui
authors.initials: CK
authors.lastname: Shao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002681:China; D019938:Cyclin D1 / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012367:RNA, Viral / Q000378:metabolism; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014763:Viral Matrix Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; C099537:Epstein-Barr virus encoded RNA 1; D012367:RNA, Viral; D014763:Viral Matrix Proteins; D019938:Cyclin D1; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C417029:EBV-encoded nuclear antigen 1