Hepatocyte nuclear factor 4A expression discriminates gastric involvement by metastatic breast carcinomas from primary gastric adenocarcinomas

Hum Pathol. 2011 Nov;42(11):1777-84. doi: 10.1016/j.humpath.2011.04.002.


Breast carcinomas sometimes metastasize to the stomach, and the histopathologic distinction of such metastases from primary gastric adenocarcinomas is often difficult. We characterized the clinicopathologic features of 21 breast carcinomas that had metastasized to the stomach and examined the use of a panel of antibodies, including hepatocyte nuclear factor 4A, for distinguishing the metastases from primary gastric diffuse-type adenocarcinomas. Histologically, all the metastatic breast carcinomas showed a poorly differentiated and/or signet ring cell morphology. Although most metastatic breast and primary gastric carcinomas contained signet ring cell components, the cases that were predominantly or exclusively composed of univacuolated-type signet ring cells were limited to metastatic breast carcinomas. Immunohistochemically, hepatocyte nuclear factor 4A was expressed in all 33 primary gastric carcinomas that were examined but was never expressed in metastatic breast carcinomas. Previously reported markers for breast and gastric carcinomas also showed a high specificity, but their sensitivities were quite variable. Estrogen receptor α, progesterone receptor, mammaglobin, and gross cystic disease fluid protein 15 were expressed in 76%, 33%, 52%, and 62%, respectively, of the metastatic breast carcinomas, whereas none of the primary gastric carcinomas expressed these antigens. CDX2, MUC5AC, MUC6, and CK20 were expressed in 36%, 85%, 27%, and 55%, respectively, of the primary gastric carcinomas. All the metastatic breast carcinomas were negative for these antibodies except for 1 case that expressed MUC5AC. Overall, the use of immunohistochemistry efficiently discriminated metastatic breast carcinomas from primary gastric carcinomas. In particular, the present study identified hepatocyte nuclear factor 4A as an excellent marker for differentiating the 2 lesions.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / pathology*
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / secondary
  • Carcinoma, Signet Ring Cell / secondary
  • Female
  • Hepatocyte Nuclear Factor 4 / biosynthesis*
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Retrospective Studies
  • Sensitivity and Specificity
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / secondary*


  • Biomarkers, Tumor
  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 4