S100A4 protein and mesothelin expression in dysplasia and carcinoma of the extrahepatic bile duct.

We evaluated the expression of S100A4 protein and mesothelin in dysplasia and carcinoma of the extrahepatic bile duct (EBD) and their potential use as adjuncts for differentiating carcinomatous and significant high-grade dysplastic epithelium from reactive or inflammatory glandular atypia of the EBD. We used immunohistochemical analysis on formalin-fixed tissue sections from 10 cases of carcinoma, 6 cases of high-grade dysphasia (HGD), 4 cases of low-grade dysplasia (LGD), and 10 cases of benign or reactive or inflammatory epithelium from the EBD. Expression of S100A4 protein was observed in 8 invasive carcinomas (80%), 5 HGD/carcinoma in situ cases (83%), and 0 LGDs. Mesothelin was expressed in 5 (50%) of 10 adenocarcinomas, 1 (17%) of 6 HGD/adenocarcinoma in situ cases, and 0 LGDs. No case of normal or reactive epithelium was positive for S100A4 protein or mesothelin. Mesothelin has moderate sensitivity and high specificity, whereas S100A4 protein is sensitive and specific for the identification of carcinoma and HGD of the EBD. S100A4 protein alone or combined with mesothelin can be used as an adjunct in differentiating carcinomatous and significant high-grade dysplastic epithelium from LGD and reactive or inflammatory glandular atypia of the EBD.

Expression of K homology domain containing protein overexpressed in cancer in pancreatic FNA for diagnosing adenocarcinoma of pancreas.

We evaluated the immunocytochemical (ICC) expression of K homology domain containing protein overexpressed in cancer (KOC) in pancreatic endoscopic ultrasound-guided fine needle aspirates (EUS-FNAs) to assess its potential use as an adjunct in differentiating nonneoplastic (GI epithelium) and benign neoplastic epithelia (benign epithelial pancreatic neoplasms) from pancreatic adenocarcinoma cells. Forty-eight cases of EUS-FNAs with histological and/or clinical follow-up data were selected for this study. Alcohol-fixed and PAP-stained slides were stained with monoclonal antibody to KOC/L523S (clone 69.1). Results were recorded as negative or positive. KOC expression was present in 35/40 (88%) of adenocarcinomas (Ac) and was negative in all eight benign cases. The sensitivity and specificity were as follows: cytology 85 and 100%, KOC 88 and 100%; combination of cytology and KOC 95 and 100%. We conclude that KOC ICC expression on alcohol-fixed smears along with cytology improves the sensitivity of EUS-FNAs in the diagnosis of pancreatic Ac, and KOC reactivity is especially useful in differentiating Ac from nonneoplastic gastrointestinal epithelium and benign neoplastic epithelia.

KOC (K homology domain containing protein overexpressed in cancer) and S100A4-protein immunoreactivity improves the diagnostic sensitivity of biliary brushing cytology for diagnosing pancreaticobiliary malignancies.

Biliary tract brush cytology is one of the favored methods of evaluating lesions of the pancreatobiliary tract. However, although its specificity has been reported to be high (91-100%), the sensitivity is lower (30-88%). In this study we applied KOC and S100A4 protein immunocytochemistry to assess their potential use as adjunct markers in differentiating benign from malignant cells, and improve the diagnostic sensitivity of this method for pancreatobiliary malignancies. The authors examined KOC and S100A4 protein expression in 44 alcohol-fixed cytology specimens obtained by biliary brushings. Diagnoses included: (1) benign/atypical favor reactive (20 cases), (2) atypical/not diagnostic of malignancy (3 cases), and (3) suspicious for malignancy/malignant (21 cases). Alcohol-fixed Papanicolaou-stained slides (PAP) were stained with monoclonal antibody to KOC/L523S and polyclonal antibody to S100A4 protein. Results were recorded as negative or positive. Twenty-four cases were confirmed positive for adenocarcinoma and 20 cases were negative. The sensitivity and specificity of cytology was 83 and 95%, KOC showed a sensitivity of 92% and specificity of 95%. S100A4 protein showed a sensitivity of 79% and a specificity of 95%. The combined use of KOC and S100A4 protein showed a sensitivity of 100% and a specificity of 95%, respectively. The concurrent use of KOC and S100A4 protein improves the diagnostic sensitivity of biliary brushings cytology and demonstrates similar specificity as cytology alone in the diagnosis of pancreatobiliary malignancy.