Does Hepatocyte Paraffin 1 expression stand a role in determining the site origin of an adenocarcinoma from unknown gastrointestinal primary?

BACKGROUND: Hepatocyte Paraffin 1 (Hep Par 1) was being extensively used to recognize the hepatocellular carcinomas, until recognition of its expression in tumors without hepatocellular differentiation.

AIMS AND OBJECTIVES: The aim of this study was to analyze if Hep Par 1 stain can serve as a specific marker of the small intestinal (SI) adenocarcinomas, versus other gastrointestinal tract (GIT) primary tumors.

MATERIALS AND METHODS: In this retrospective cross-sectional study, normal GIT mucosa (n - 60), corresponding adenocarcinomas (n - 60) and nodal metastatic foci (n - 60) from the same patients, including 10 cases each from the esophagus, stomach, SI periampullary region, colon, rectum, and gall bladder were included. H-score was calculated by multiplying the stain distribution and intensity scores. The H-scores were compared with other clinical and histological parameters.

RESULTS: While normal SI mucosa showed diffuse strong Hep Par 1 staining, normal esophageal and gastric epitheliums were negative and normal colon, rectal, and biliary epithelium showed weak focal positivity. Adenocarcinomas from all these sites, however, showed Hep Par 1 expression, irrespective of the tumor type, site or origin, and tumor stage. The corresponding metastatic sites also showed variable Hep Par 1 positivity, without any site specificity.

CONCLUSION: Hep Par 1 stain cannot help to determine the exact site of origin of primary GIT tumors. Its expression in adenocarcinomas across the GIT and their metastatic foci proves that it cannot be regarded as a marker of SI differentiation, especially in malignancy.