Loss of p16/CDKN2A tumor suppressor protein in gastric adenocarcinoma is associated with Epstein-Barr virus and anatomic location in the body of the stomach

Hum Pathol. 2000 Jan;31(1):45-50. doi: 10.1016/s0046-8177(00)80197-5.


Gastric adenocarcinomas (n = 125) were analyzed by immunohistochemistry for the presence of p16, the CDKN2A gene product. This protein was lost in 31 of 125 cases (25%), and loss was associated with location of the tumor in the body of the stomach (P = .001). Loss of p16 was also associated with the presence of Epstein-Barr virus (EBV) in tumor cells as determined by in situ hybridization (P = .022). This effect may relate to anatomic site, because EBV-associated tumors originate more frequently in the body of the stomach. When p16 status was evaluated for ethnic origin of the patient (non-Hispanic white, Hispanic, or black), a strong trend (P = .057) was found for African-American patients to have fewer p16-negative tumors than other patients. This also may relate to anatomic location, because fewer tumors from black patients arose in the body of the stomach (P = .022). No significant associations were detected between p16 status and histological subtype (intestinal v diffuse), the presence of microsatellite instability, grade or stage of the tumor, or age, gender, or survival of the patient. In conclusion, p16 loss is quite common in gastric adenocarcinoma, and such loss is more common in EBV-infected tumors arising in the body of the stomach.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / virology*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • RNA, Viral / metabolism
  • Stomach / pathology
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / virology*


  • Cyclin-Dependent Kinase Inhibitor p16
  • Epstein-Barr virus encoded RNA 1
  • RNA, Viral