Immunohistochemical staining of hepatocellular carcinoma with monoclonal antibody against inhibin

Abstract

Inhibin is a peptide hormone produced by ovarian granulosa cells. During a recent study investigating the immunohistochemical staining of ovarian granulosa cell tumours and other neoplasms with an anti-inhibin monoclonal antibody, we identified strong cytoplasmic staining of hepatocytes. In the present study we investigated the immunostaining of hepatocellular carcinoma and other neoplasms involving the liver with anti-inhibin to determine whether the antibody may be of value in the differential diagnosis of hepatic neoplasms. Immunostaining for alpha-fetoprotein was also performed. With anti-inhibin there was positive, generally strong, cytoplasmic staining of 17 of 19 cases of hepatocellular carcinoma, including the pleomorphic and glandular variants. There was positive staining of six of 20 cases of adenocarcinoma. In these, positive staining was generally focal, of weak intensity and involved the luminal surface of neoplastic glands. There was no staining of five cases of neuroendocrine tumour. There was positive staining for alpha-fetoprotein in 13 of 19 cases of hepatocellular carcinoma and in two of 20 cases of adenocarcinoma but no staining of neuroendocrine tumours. Immunostaining with anti-inhibin antibody may be of value in the differentiation of hepatocellular carcinoma from other neoplasms involving the liver. The antibody is a more sensitive, but less specific, immunohistochemical marker for hepatocellular carcinoma than is alpha-fetoprotein.

Surveillance and diagnosis of hepatocellular carcinoma in patients with cirrhosis

“…AFP AFP is a fetal-specific glycoprotein with a molecular weight of 70 kDa, whose synthesis declines rapidly after birth. The immunohistochemical use of AFP staining has very low sensitivity as it detects just 17%-68% of malignant hepatocellular lesions when used alone [89][90][91][92][93][94][95][96][97][98][99][100][101][102][103] . In a study by Murakata et al [104] there was no staining of clear-cell HCC.…”

“…In a study by Murakata et al [104] there was no staining of clear-cell HCC. However, the specificity of AFP is high with an average value of 97% [89,92,93,95,96,99,101,104] .…”

Immunohistochemical and Molecular Markers in the Diagnosis of Hepatocellular Carcinoma

“…6 Almost all hepatoid adenocarcinomas, primary as well as metastatic, are reported as AFP positive. 19 Nevertheless, specificity is high (97%) 8 in that only 0%-10% of CC and mAdC immunostain, 7,9,10,28,59,61,62 and clear-cell renal cell carcinomas are all shown to be immunonegative. 6…”

“…Immunoreactivity reported in 90% of HCC and in nonneoplastic liver 61 has been shown to be falsepositive staining caused by endogenous biotin. 74…”

Inhibin Is Not an Immunohistochemical Marker for Hepatocellular Carcinoma: An Example of the Potential Pitfall in Diagnostic Immunohistochemistry Caused by Endogenous Biotin

“…The anti-inhibin primary antibody used in the present study, therefore, was of the same specificity, clonal source, and titer as that used in the previously referenced study. 9 By using a similar microwave antigen retrieval technique as the previous investigators, immunostaining for inhibin was performed as follows with the inclusion of a step to block endogenous biotin activity. Microwave antigen retrieval was performed in a 10-mmol/L concentration of citrate buffer, pH 6.0, for 20 minutes at high power (800 W).…”