Diagnostic Implications of Albumin Messenger RNA Detection and Cytokeratin Pattern in Benign Hepatic Lesions and Biliary Cystadenocarcioma

Abstract

Cytokeratin (CK) patterns and albumin messenger RNA (mRNA) are investigated in 24 patients with benign hepatic lesions (7 patients with focal nodular hyperplasia [FNH], 10 with hepatocellular adenomas [HA], 1 with biliary hamartoma, 4 with biliary cysts, 2 with cystadenomas) and in 8 patients with cystadenocarcinoma, a rare liver malignancy. The lesions and surrounding tissue of the hepatocytic components expressed CK 8 and 18 at immunohistochemistry, whereas the biliary elements evidenced CK 8 and 18 and CK 7 and 19. The albumin mRNA, as detected by in situ hybridization (ISH), revealed different distributions in the hepatocytes of FNH and HA. In the benign biliary lesions, the normal hepatocytes surrounding the tumors expressed albumin mRNA, whereas the biliary structures did not. Interestingly, in the cystadenocarcinomas, albumin mRNA was observed not only in the hepatocytes of residual parenchyma, but also in neoplastic bile duct cells lining the carcinomatous cysts; no signal was identified in the nonneoplastic biliary elements. This indicates that cystadenocarcinomas have a mixed biological phenotype and suggests they could arise either from pluripotent cells or from neoplastic cells that reacquire epigenetic features. Our results suggest two possible diagnostic applications for albumin ISH: on routine sections, it could represent an important tool for distinguishing between cystadenoma and cystadenocarcinoma; and on fine needle biopsy specimens, it could reduce uncertainty between FNH and HA.

Branched Chain In Situ Hybridization for Albumin as a Marker of Hepatocellular Differentiation

“…(3, 4, 9, 12-14, 22) The current in situ hybridization platform, however, differs considerably from the albumin ISH assay introduced in the 1990s. In this prior assay, oligonucleotide probes were labeled with digoxigenin while the current assay amplifies the mRNA signal using branched DNA amplification, theoretically allowing for the detection of a single copy of RNA and considerably increasing the sensitivity of the assay.…”

“…(3, 4, 9, 12-14) However, despite the fact that albumin has the potential to be a highly sensitive and specific marker for HCC, it has not found widespread use in the diagnostic laboratory, driven by two unresolved problems: 1) the theoretical possibility that mRNA degrades far more quickly than proteins, and hence a mRNA based biomarker is likely to be less sensitive than immunohistochemistry, and 2) lack of a robust and sensitive automated platform for the detection of RNA that could be adapted for the clinical laboratory.…”

Cystic Neoplasms of the Liver: Biliary Cystadenoma and Cystadenocarcinoma

“…(64, 69, 80) CEA is localized to the luminal surface of BCA epithelial cells whereas BCAC epithelium have CEA diffusely within the cytoplasm. (81) D'Errico and colleagues (82) noted markedly increased albumin messenger RNA in all 8 BCAC lesions they investigated while noting its absence in BCA and other benign biliary cysts.…”

Hepatocellular carcinoma with characteristic mucin production: a case report

“…D’Errico et al have reported focal positivity for albumin mRNA in four of six peripheral CCs, as well as in biliary cystadenocarcinomas even without the morphological evidence of hepatocellular carcinoma differentiation in these cases [10]. Even the border between pure HCCs and pure CCs could be blurred by the immunohistochemical assessment on the phenotype expression.…”