Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At present, there is no case report of HHV8- primary effusion lymphoma (PEL) with t(9;14)(p13;q32) involving both PAX-5 and immunoglobulin heavy chain gene rearrangement, which is a rare translocation in B-cell non-Hodgkin's lymphoma, in an HIV- patient. We examined an HIV-seronegative 63-year-old Japanese man with hepatitis C virus-associated liver cirrhosis and hepatocellular carcinoma manifesting peritoneal lymphomatous effusion without tumor mass at any body site. The lymphoma cells were examined twice by light microscopy, immunohistochemistry, three-color flow cytometry, cytogenetics, and molecular analyses. The nuclear morphology of lymphoma cells was similar to that of large noncleaved cells, although the lymphoma cell size was a little smaller that of the usual large-cell lymphoma. Immunophenotyping of lymphoma cells in the ascitic fluid revealed a mature peripheral B-cell phenotype (CD5- CD10- CD19+ CD20+ CD22+ Ig G+ lambda+). Cytogenetics showed a clonal population: 45,X,-Y, der(2) t(2;6)(q31;p21.3), t(4;8)(q21;q11.2), der(6) t(2;6)(q31;p21.3) add(6)(q15), t(9;14)(p13;q32.3) [10]/47, idem, +der(6) t(2;6), +16[10]. Southern blot analysis revealed rearranged fragments with a probe for immunoglobulin heavy chain, some of which were a size similar to those with a PAX-5 gene probe. Polymorphism, not rearrangement, of the c-MYC gene, was also found. HHV8 and the Epstein-Barr virus were not detected by polymerase chain reaction. This case is the first report of an HHV8- PEL with t(9;14) involving a PAX-5 gene rearrangement in an HIV-seronegative patient. This primary effusion lymphoma manifested spontaneous regression without any therapy. These findings suggest that there may be an additional subcategory of primary effusion lymphoma that is not associated with HHV8 nor c-MYC(R) but is pathogenetically associated with the PAX-5 gene or hepatitis C virus.
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PMID:Herpes virus type 8-negative primary effusion lymphoma associated with PAX-5 gene rearrangement and hepatitis C virus: a case report and review of the literature. 1063 3

The histological diagnosis of hepatocellular carcinoma (HCC) can be complicated by difficulty in differentiation from cholangiocarcinoma and metastatic carcinoma. Immunohistochemical stains currently in use are suboptimal in terms of specificity and sensitivity. Using cDNA array analysis for differential gene expression, we demonstrated a significant increase in mRNA expression level of CD10/CALLA, a type 2 cell-surface metalloproteinase, in HCC, which was subsequently confirmed by reverse transcriptase-polymerase chain reaction and Western blotting analysis. To test the possibility of using CD10/CALLA as a diagnostic marker for HCC, various intrahepatic tumors were studied immunohistochemically using a monoclonal antibody for CD10. A characteristic canalicular-staining pattern was observed in normal hepatocytes and at the apical surface of bile duct epithelial cells. The canalicular expression of CD10 was identified in 9 of 15 HCCs examined (60%), whereas 10 cholangiocarcinomas and 8 of 9 metastatic carcinomas lacked this staining. In three of the six HCCs negative for CD10, the surrounding nonneoplastic liver tissue was also negative, suggesting fixation-associated loss of immunoreactivity. Six HCCs had stronger CD10 staining in tumor cells when compared to the surrounding nonneoplastic tissue. Three cases of benign bile duct adenomas also expressed CD10 at the luminal aspect. One of the MCs showed a diffuse, cytoplasmic staining for CD10, a pattern readily distinguishable from that of HCC. A panel of other immunohistochemical markers were also studied for comparison, including polyclonal anti-carcinoembryonic antigen, cytokeratin (CK) 7, CK20, and alpha-fetoprotein. Our results demonstrate that cDNA arrays can be effectively used to identify new diagnostic markers, and that CD10 is a reliable marker for identifying HCC, particularly when used in conjunction with a panel of immunohistochemical markers (polyclonal anti-carcinoembryonic antigen, CK7, CK20, and alpha-fetoprotein) and in the distinction from cholangiocarcinoma.
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PMID:cDNA arrays and immunohistochemistry identification of CD10/CALLA expression in hepatocellular carcinoma. 1158 69

Neprilysin (CD10) is expressed in both normal and neoplastic liver tissue, where it exhibits a characteristic canalicular pattern (CD10can) similar to the one observed when antibodies cross-react with biliary glycoprotein I (p-CEA). The aim of this retrospective study was to investigate the use of CD10can in differentiating between hepatocellular carcinomas (HCCs; 63 specimens) and nonhepatocellular carcinomas (non-HCCs) metastatic to the liver (non-HCC; 25 specimens). Immunostaining was performed with antibodies directed against CD10, p-CEA, and alpha-fetoprotein (AFP). Albumin mRNA was detected by nonradioactive in situ hybridization (ISHalbumin). In the HCC group a canalicular staining pattern for CD10 was found in 43 (68.3%) specimens. AFP was found in 15 (23.8%) specimens, and a canalicular staining pattern for p-CEA was present in 60 (95.2%) specimens. ISHalbumin was performed in 35 HCC specimens and showed labeling of tumor cells in 30 (85.7%) specimens. In the non-HCC group, CD10can, and p-CEA, immunostaining for AFP and labeling for ISHalbumin were confined to non-neoplastic liver tissue. Sensitivity and specificity were, respectively, 68.3% and 100% for CD10can, 23.8% and 100% for AFP, 95.2% and 100% for canalicular p-CEA, and 86.4% and 100% for ISHalbumin. Our results demonstrate that canalicular staining for CD10 is a highly specific marker of hepatocytic differentiation. Although it does not differentiate between benign and malignant lesions, CD10can is clearly useful in differentiating between HCC and non-HCC.
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PMID:Canalicular immunostaining of neprilysin (CD10) as a diagnostic marker for hepatocellular carcinomas. 1168 65

We describe a case of primary nonfunctioning paraganglioma that, unlike any other previously reported case, was strictly confined to the liver and must therefore have arisen on liver parenchyma. An asymptomatic 46-year-old man was referred to us for laparotomy and a right hemihepatectomy after a preoperative diagnosis of fibrolamellar hepatocellular carcinoma, based on a fine-needle biopsy. An 8-cm resiliently firm, pale gray nodule with a large central area of fibrosis and a thin fibrous capsule was resected. The polygonal eosinophilic tumor cells containing round nuclei lacking nucleoli were arranged in small nests set in a vascularly rich stroma. At immunohistochemistry neoplastic cells were strongly positive for chromogranin A, neuron-specific enolase, synaptophysin, and IGF-II protein; they were negative for keratin, S-100 protein, CD10, vimentin, and smooth muscle actin. In situ hybridization confirmed that, as in other sites, liver paraganglioma can express IGF-II gene. Conversely (and unlike hepatocellular carcinomas), the neoplastic cells did not express albumin mRNA, which was detected only in surrounding hepatocytes. The clinical course was benign and the patient is well and free of neoplastic disease 9 years after surgery. Knowledge of the entity should avoid possible confusion with hepatocellular carcinoma, especially of the fibrolamellar variety.
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PMID:Primary paraganglioma strictly confined to the liver and mimicking hepatocellular carcinoma: an immunohistochemical and in situ hybridization study. 1213 Nov 64

Hepatocyte monoclonal antibody (Hep) (alternatively Hep Par 1 for Hep paraffin 1) has been reported to stain normal hepatic tissue and hepatocellular carcinoma (HCC) with high specificity. We have studied the Hepatocyte expression in 96 cases of HCC and 311 cases of nonhepatic epithelial tumors. All cases of HCC were also stained with CEA-Gold 5, CD10, and alpha-fetoprotein. Hep, CEA-Gold 5, CD10, and alpha-fetoprotein immunostains were performed on formalin-fixed, paraffin-embedded tissue sections. Hep immunoreactivity was detected in 88 of 96 cases of HCC (92%), with a cytoplasmic and granular pattern of staining. The level of Hep expression in HCC corresponded to the nuclear grade and growth pattern. All 50 cases of nuclear grade 1 and nuclear grade 2 HCC were positive (100%), whereas 37 of 44 nuclear grade 3 (84%) and 1 of 2 nuclear grade 4 (50%) were positive. Sixty-seven of 68 cases of HCC with a trabecular, pseudoglandular, or scirrhous growth pattern were positive (98%), whereas 22 of 27 cases of HCC with a compact growth pattern were positive (81%). CEA-Gold 5, CD10, and alpha-fetoprotein immunoreactivity was detected in 76% (73 of 96), 52% (50 of 96), and 31% (30 of 96) cases of HCC, respectively. The positive predictive value of the combination of all four antibodies was 97%. Three cases of HCC were negative for all four antibodies; these cases had a high nuclear grade or a sarcomatoid or compact growth pattern. Twenty of 311 cases of nonhepatic tumors were positive for Hep (6%): 15 were adenocarcinomas and five were neuroendocrine tumors. The negative predictive value of Hep in HCC was 94%. The Hep-positive nonhepatic epithelial tumors were easily distinguished from HCC by the expression of keratin 7 or keratin 20 for adenocarcinoma and chromogranin and synaptophysin for neuroendocrine tumors because HCC does usually not express these markers. With the exception of two cases of hepatoid gastric carcinoma, all Hep-positive nonhepatic epithelial tumors were negative for alpha-fetoprotein, CEA-Gold 5, and CD10. Our study demonstrates that Hep is a relatively specific marker for HCC. It is useful in differentiating HCC from primary hepatic cholangiocarcinoma and metastatic tumors when combined with other immunomarkers.
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PMID:Hepatocyte antigen as a marker of hepatocellular carcinoma: an immunohistochemical comparison to carcinoembryonic antigen, CD10, and alpha-fetoprotein. 1217 84

The distinction of hepatocellular carcinoma (HCC) from metastatic adenocarcinoma (MA) and cholangiocarcinoma (CC) in some cases requires the use of immunohistochemistry. CD10 has recently been suggested as a useful stain for HCC. We directly compared CD10 with other immunohistochemical markers, Hepatocyte, pCEA, and MOC31, that have previously shown to be useful for the distinction between tumors in the liver to help define the current panel of stains that most readily distinguishes HCC from CC and MA. One hundred previously well-characterized tumors in the liver were evaluated and included 25 HCC, 15 CC, and 60 MAs (15 each from breast, esophageal/gastric, pancreatic, and colorectal origin). Tumors were immunostained with the commercially available antibodies Hepatocyte, pCEA, MOC31, and CD10. CD10 stained 13 of 25 HCC and was rarely positive in MA and CC (3/75). Hepatocyte stained 24 of 25 HCC and was negative in all 75 MA and CC. pCEA stained 24 of 25 HCC and 71 of 75 MA and CC with the proper pattern of immunoreactivity, but the pattern of staining was difficult to interpret in several cases. MOC31 stained 1 of 25 HCC and 65 of 75 MA and CC. Hepatocyte was the most sensitive and specific single marker for HCC. CD10 is not a useful addition or substitution to the panel of Hepatocyte, MOC31, and pCEA. The combination of Hepatocyte, MOC31, and pCEA correctly classified 99 of 100 tumors in this study and is our proposed panel of immunostains for the initial workup of malignant tumors in the liver.
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PMID:A comparison of CD10 to pCEA, MOC-31, and hepatocyte for the distinction of malignant tumors in the liver. 1248 Oct 8

Distinguishing hepatocellular carcinoma (HCC) from cholangiocarcinoma (CC) and metastatic adenocarcinoma (MA) involving the liver can be problematic, often requiring the use of immunohistochemistry to facilitate diagnosis. Hep Par 1, a monoclonal antibody with expression confined primarily to benign and malignant hepatocytes, has recently become commercially available. We evaluated Hep Par 1 along with other immunohistochemical markers used to differentiate HCC, CC, and MA, including AE1/AE3, CAM 5.2, B72.3, monoclonal carcinoembryonic antigen (mCEA), polyclonal CEA (pCEA), alpha-fetoprotein (AFP), factor XIIIa, inhibin, CD10, villin, MOC-31, cytokeratin (CK) 7, CK 19, and CK 20, to determine the markers most useful in differentiating these entities. Forty-two cases of HCC, 9 cases of CC, and 56 cases of MA (24 colon, 15 pancreas, 8 ovary, 5 breast, and 4 stomach) were studied. Hep Par 1 was sensitive and specific for HCC, with 38 of 42 (90%) cases staining positively, whereas reactivity was observed in only 8 of 56 (14%) MAs and 0 of 9 CCs. Though limited somewhat by poor sensitivity, a bile canalicular pattern of staining with pCEA, CD10, and villin was specific for HCC and was not observed in the other tumors. Lack of mCEA and MOC-31 immunoreactivity was also characteristic of HCCs. CK 19 positivity favored CC over HCC, but was not useful in differentiating CC from MA. Expression of AFP, although observed in only about one third of the cases, favored HCC over CC and MA. CK 7 and CK 20 were also useful in this differential diagnosis, particularly when dealing with MA of colonic origin. AE1/AE3, CAM 5.2, B72.3, inhibin, and factor XIIIa were noncontributory in differentiating these entities.
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PMID:Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma. 1251 85

A well-characterized positive marker for hepatocellular differentiation would be a useful tool for the diagnosis of hepatocellular carcinoma (HCC). The recently commercially available Hep Par 1 antibody (clone OCH1E5.2.10) has been reported to be a sensitive marker for HCC in paraffin embedded sections. Of non-hepatocellular tumors, occasional carcinomas have been reported to stain, most frequently gastric adenocarcinomas. This study further evaluated the staining of this antibody on a large number of neoplasms using tissue microarray technology as well as conventional tissue sections. Six hundred seventy-six tumors, including 19 cases of HCC, were tested. Eighteen of 19 cases of HCC were positive, 3 showing <5% staining. Two cases negative on the array showed focal staining when whole tissue sections from the same tumors were used. 16 of 34 cases of gastric carcinomas gave positive reactions, 4 of these showed less than 5% staining. Staining of gastric carcinomas was not limited to signet ring-type carcinomas or to areas of hepatoid differentiation. Only 1 of 11 cases of cholangiocarcinoma showed focal staining. We also noted several other tumors to stain occasionally, including adrenal cortical carcinoma (3/13), yolk sac tumor (2/9), colonic adenocarcinoma (8/106), lung carcinoma (3/52), ovarian carcinoma (5/48), and endocervical adenocarcinoma (1/5). We did not observe staining in pancreatic carcinoma (11), renal cell carcinoma (36), breast carcinoma (85), melanoma (25), or mesothelioma (5). This study supports Hep Par 1 as a useful marker in the differential diagnosis of HCC, but with significant limitations. Cautious use of this antibody in a panel with other positive (alpha fetoprotein, CD10, polyclonal carcinoembryonic antigen) and negative (epithelial membrane antigen, monoclonal carcinoembryonic antigen, CD15) markers of hepatocellular differentiation may aid in the accurate diagnosis of HCC.
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PMID:Hep par 1 antibody stain for the differential diagnosis of hepatocellular carcinoma: 676 tumors tested using tissue microarrays and conventional tissue sections. 1259 66

We performed immunohistochemical staining against Hepatocyte (Hep) and CD10 antibodies in 75 hepatocellular carcinoma (HCC), 50 cholangiocarcinomas, 49 colorectal adenocarcinomas, and 308 gastric adenocarcinomas by tissue array method. We also evaluated the various non-neoplastic adult tissues and fetal digestive organs. Hep was expressed in 80% of HCCs, and HCCs without Hep expression were more likely to have a higher Edmondson & Steiner grade than HCCs with Hep expression (p=0.004). In non-HCCs, 16% of cholangiocarcinomas, 8.2% of colorectal carcinomas, and 44.2% of gastric carcinomas expressed Hep. Gastric carcinomas with Hep expression were significantly associated with early gastric carcinomas (p<0.001). In non-neoplastic tissues, Hep was found expressed in normal hepatocytes, small intestinal mucosa, and intestinal metaplasia of the stomach. Fetal hepatocytes expressed Hep after 19 weeks of gestation. CD10 was detected in 46.7% (35/75) of HCCs, and canalicular staining pattern was predominant in HCCs. In conclusion, the expression of Hep and CD10 may help to distinguish HCCs from non-HCCs.
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PMID:Hepatocyte expressions in hepatocellular carcinomas, gastrointestinal neoplasms, and non-neoplastic gastrointestinal mucosa: its role as a diagnostic marker. 1467 41

Differentiating primary and metastatic hepatic malignancies can be diagnostically challenging in fine-needle aspiration cytology (FNAC). We compared four immunohistochemical (IHC) markers, pCEA, CD10, HepPar1, and CD34, in differentiating hepatocellular carcinoma (HCC) from metastatic carcinoma (MC) in FNAC specimens. Sixty cases of liver FNAC with their corresponding cell blocks were retrieved from the hospital computer system, including 30 HCC and 30 MC (15 colon, 10 breast, and 5 pancreas). The diagnoses were confirmed by clinical follow-up and surgical resection or core needle biopsy. The direct cytologic smears were air-dried and Diff-Quik-stained, and alcohol-fixed and Papanicolaou-stained. Cell block sections from the aspirates were immunostained for pCEA, CD10, HepPar1, and CD34. IHC on cytologic smears for HCC was performed on 10 cases and compared with the cell block results. In HCC, CD10, and pCEA demonstrated the characteristic canalicular staining in 23/30 (77%) and 24/30 (80%) of the cases, respectively; however, none of the MC showed a canalicular staining pattern. HepPar1 was positive in 26/30 (87%) of the HCC cases and one MC. CD34 stained sinusoidal endothelial cells in 27/30 (90%) cases of HCC and six MC. Our results demonstrate that the canalicular staining pattern for CD10 and sinusoidal staining pattern of CD34 are very specific, in addition to the high specificity and sensitivity of HepPar1 for HCC. Cell blocks were more informative in demonstrating the characteristic architecture and immunostaining pattern of the malignancy than the cytologic smears. An IHC panel consisting of pCEA, CD10, HepPar1, and CD34 is useful for confirming HCC in FNAC of the liver.
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PMID:Diagnostic value of HepPar1, pCEA, CD10, and CD34 expression in separating hepatocellular carcinoma from metastatic carcinoma in fine-needle aspiration cytology. 1469 37


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