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

We performed immunohistochemical studies on 90 surgically resected liver tumors, including 30 tumors each from hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and metastatic colorectal adenocarcinoma (MCA), using monoclonal antibodies against cytokeratin (CK) 7, CK 19, and CK 20 to examine the differences in the CK expressions in primary and metastatic carcinomas of the liver. We also investigated the usefulness of such expression in the differential diagnosis in addition to existing markers such as alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9. For CK 7, all except for one (97%) of the CCs were diffusely positive, whereas only two (7%) HCCs and one (3%) MCAs were diffusely positive. For CK 19, 23 (77%) CCs and 19 (64%) MCAs were diffusely positive, whereas no HCCs were positive. For CK 20, 22 (74%) MCAs were diffusely positive, whereas no HCC and three (10%) CCs were diffusely positive. The findings concerning the expression of immunohistochemical CK are therefore considered to be useful in addition to the diagnostic criteria when making a differential diagnosis of primary and metastatic carcinomas of the liver.
 ...
PMID:The expression of cytokeratins 7, 19, and 20 in primary and metastatic carcinomas of the liver. 887 22

Distinguishing hepatocellular carcinoma (HCC) from metastatic adenocarcinoma (MA) and cholangiocarcinoma (CC) can, at times, be difficult and sometimes requires immunohistochemical analysis. Recently, MOC31, an antibody directed against a cell surface glycoprotein, has been shown to be useful in separating HCC from both MA and CC; however, no study has compared MOC31 and other frequently used immunostains. We compare MOC31 with other commonly used immunostains for HCC, MA, and CC. Formalin-fixed, paraffin-embedded tissue sections from 57 previously characterized hepatic neoplasms (13 HCC, 14 CC, 3 combined HCC-CC, and 27 MA) were immunostained with antibodies directed against MOC31, cytokeratin (CK) 7, CK20, alpha-fetoprotein (AFP), polyclonal carcinoembryonic antigen, Ber-EP4, and Factor XIII-A. Two pathologists reviewed slides, and positivity was defined as more than 1% of cells staining with the appropriate pattern. Positive MOC31 immunostaining was seen in 0 of 13 HCC, 13 of 14 CC, 3 of 3 HCC-CC, and 27 of 27 MA; the staining was strong and diffuse. CK20 reactivity was observed in 0 of 13 HCC, 2 of 14 CC, 0 of 3 HCC-CC, and 12 of 27 MA; CK7 immunostained 4 of 13 HCC, 13 of 14 CC, 3 of 3 HCC-CC, and 15 of 27 MA; AFP was detected in 4 of 13 HCC and 2 of 3 HCC-CC, whereas all CC and MA were negative; polyclonal carcinoembryonic antigen showed immunoreactivity in 12 of 13 HCC and 3 of 3 HCC-CC in a canalicular pattern, whereas diffuse positivity was identified in 13 of 14 CC and 26 of 27 MA; Ber-EP4 immunostained 1 of 13 HCC, 14 of 14 CC, 2 of 3 HCC-CC, and 26 of 27 MA; and Factor XIII-A was negative in all HCC, CC, and MA. MOC31 expression distinguished HCC from adenocarcinoma in 56 of 57 cases. AFP was specific for HCC but was not sensitive. CK7 and CK20 have limited utility in distinguishing HCC from CC or MA, and Factor XIII-A is not useful. Ber-EP4 staining was similar to MOC31, but one HCC did stain with Ber-EP4. Polyclonal CEA yields similar numerical results as MOC31, but the focal nature of the staining and occasional difficulty in evaluating the pattern can make interpretation problematic. We conclude that MOC31 should be a component of the immunohistochemical panel to distinguish HCC from CC and MA.
 ...
PMID:Immunohistochemical analysis of hepatocellular and adenocarcinoma in the liver: MOC31 compares favorably with other putative markers. 1091 37

Cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) are low molecular weight cytokeratins. Their anatomic distribution is generally restricted to epithelia and their neoplasms. We surveyed 435 epithelial neoplasms from various organ systems by immunohistochemistry using CK 7 and CK 20 monoclonal antibodies. Expression of CK 7 was seen in the majority of cases of carcinoma, with the exception of those carcinomas arising from the colon, prostate, kidney, and thymus; carcinoid tumors of the lung and gastrointestinal tract origin; and Merkel cell tumor of the skin. The majority of cases of squamous cell carcinoma of various origins were negative for CK 7, except cervical squamous cell carcinoma, in which 87% of cases were positive. Approximately two thirds of cases of malignant mesothelioma were CK 7-positive. CK 20 positivity was seen in virtually all cases of colorectal carcinomas and Merkel cell tumors. CK 20-positive staining was also observed in cases of pancreatic carcinomas (62%), gastric carcinoma (50%), cholangiocarcinomas (43%), and transitional cell carcinomas (29%). The expression of CK 20 was virtually absent in carcinomas from other organ systems and in malignant mesothelioma. CK 7- and CK 20-negative epithelial neoplasms included adrenal cortical carcinoma, germ cell tumor, prostate carcinoma, renal cell carcinoma, and hepatocellular carcinoma.
 ...
PMID:Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. 1100 36

A variable proportion of bile duct adenomas of the liver are still confused with metastatic well-differentiated adenocarcinoma by surgeons and pathologists. We present here three examples of previously undescribed primary hepatic bile duct tumors that were composed almost entirely of clear cells that closely mimicked metastatic renal cell carcinoma. They were interpreted as atypical bile duct adenomas and occurred in two males and one female whose ages ranged from 25 to 64 years. All three tumors were incidental findings and measured from 0.8 to 1.1 cm. The clear neoplastic cells showed mild nuclear atypia and no mitotic activity. They were arranged in tubules and nests that focally infiltrated the hepatic parenchyma. For comparison, a case of clear cell cholangiocarcinoma and 13 conventional bile duct adenomas were examined. The clear cell cholangiocarcinoma was larger (6.0 cm) and had the tubular pattern of conventional cholangiocarcinoma and an abundant desmoplastic stroma. The clear cells of this tumor exhibited greater nuclear atypia and increased mitotic activity. All three atypical bile duct adenomas expressed cytokeratin (CK) 7, p53 protein, epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA); they were negative for CK20, vimentin, Hep Par 1, chromogranin, and prostatic specific antigen (PSA) and exhibited less than 10% of Ki-67-positive nuclei. One atypical bile duct adenoma displayed luminal immunoreactivity for villin. With the exception of Ki-67 reactivity, the 13 conventional bile duct adenomas and the clear cell cholangiocarcinoma had essentially a similar immunohistochemical profile as that of the atypical clear cell bile duct adenomas. The absence of an extrahepatic primary tumor, the histologic features, the immunohistochemical profile, and the fact that all patients are symptom-free 2 months to 18 years after wedge liver biopsy support the interpretation of atypical clear cell bile duct adenoma. The differential diagnosis with clear cell hepatocellular carcinoma and metastatic clear cell carcinomas is discussed.
 ...
PMID:Atypical bile duct adenoma, clear cell type: a previously undescribed tumor of the liver. 1142 Apr 69

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.
 ...
PMID:cDNA arrays and immunohistochemistry identification of CD10/CALLA expression in hepatocellular carcinoma. 1158 69

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.
 ...
PMID:Hepatocyte antigen as a marker of hepatocellular carcinoma: an immunohistochemical comparison to carcinoembryonic antigen, CD10, and alpha-fetoprotein. 1217 84

Combined hepatocellular-cholangiocarcinoma (CHC) forms a small but significant proportion of primary liver carcinomas. However, its diagnostic features are not well established, and this has possibly contributed to the variability in its reported clinical outcome in the literature. Many such tumors with features intermediate between hepatocellular carcinoma and cholangiocarcinoma (CC) may have been considered CC in the past based on positivity for "biliary differentiation" cytokeratins and the lack of availability of highly sensitive and specific hepatocellular markers. The utility of in situ hybridization for albumin mRNA, a recently available sensitive and specific hepatocellular marker, has not been reported in CHC. We investigated 27 CHCs with regard to their histomorphologic spectrum and association of these morphologies with immunohistochemical staining for different cytokeratins (CK7, CK19, and CK20; AE1; Cam 5.2), epithelial membrane antigen, polyclonal carcinoembryonic antigen and alpha-fetoprotein, and in situ hybridization for albumin mRNA. All 27 tumors contained areas morphologically intermediate between hepatocellular carcinoma and CC (transitional-type tumors), and in each case such areas formed at least 25% of the tumor. Nine (33%) tumors showed areas with "antler-like" morphology, a feature not previously described in CHC. Twenty-two of 23 tumors (96%) showed positive signals on in situ hybridization for albumin mRNA. Positivity for both hepatocellular (albumin mRNA) and biliary (keratin immunohistochemical profile) markers confirmed the light microscopic impression of biphenotypic differentiation in these tumors. Immunohistochemical positivity for all cytokeratins (except CK7) and epithelial membrane antigen, as well as the expression of albumin mRNA by in situ hybridization, did not show significant differences between hepatocellular carcinoma and CC-like areas. Based on the cytokeratin profile and results on polyclonal carcinoembryonic antigen/alpha-fetoprotein alone, many such tumors would be classified as CC. However, the positivity for albumin mRNA by in situ hybridization proves that such an interpretation would not have been accurate. Clinically, CHCs showed many differences from pure hepatocellular carcinoma, including the absence of cirrhosis (0 of 27), rarity of serum hepatitis B or C marker positivity (4 of 27), and normal to only mildly elevated serum alpha-fetoprotein levels (median 187 ng/mL). The tumor followed an aggressive clinical course, with overall 3-and 5-year survival rates of 30% and 18%, and in the resected cases of 38% and 24%, respectively.
 ...
PMID:Combined hepatocellular-cholangiocarcinoma: a histopathologic, immunohistochemical, and in situ hybridization study. 1217 85

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.
 ...
PMID:Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma. 1251 85

Hepatoid adenocarcinoma (HAC) is a special type of extrahepatic adenocarcinoma, which has a striking morphologic similarity to hepatocellular carcinoma. Seven HACs arising in the stomach and one in the lung, all with liver metastasis, were studied. They shared clinical features, such as old age, high serum alpha-fetoprotein level, aggressive behavior, and hepatic tumor in absence of risk factors for hepatocellular carcinoma (HCC). Morphologically, tumors were characterized by an admixture of tubulo-and/or papillary adenocarcinoma with hepatoid foci. In six cases, liver metastases showed an exclusive hepatoid differentiation, virtually indistinguishable from HCC with solid growth pattern. As HAC and HCC cannot be differentiated on the basis of morphology alone, differences in immunohistochemical reaction patterns would be of considerable diagnostic help. Immunostaining for CK7, CK8, CK18, CK19, CK20, alpha-fetoprotein, p-CEA, and HepPar1 revealed that hepatoid areas of both primary and metastatic HAC have a specific immunoprofile, distinctive of this entity. On the one hand, positivity of virtually all HACs for alpha-fetoprotein, CK8, CK18, and the membranous, canalicular staining for polyclonal carcinoembryonic antigen underline its hepatoid nature. On the other hand, positive staining for CK19 and CK20 and frequent negativity for HepPar1 in both primary tumors and their metastases were distinctive features of HAC. Furthermore, HAC differs from combined hepatocellular cholangiocarcinoma, being negative for CK7. In addition, for comparison of immunohistochemical results, we stained with the same antibody panel a tissue microarray of 121 HCCs. Comparative genomic hybridization study of three HAC supports their hepatoid differentiation as aberrations found in HAC are common in HCC (4q-, 8p-), and hepatoblastoma (Xq+), respectively.
 ...
PMID:Hepatoid adenocarcinoma with liver metastasis mimicking hepatocellular carcinoma: an immunohistochemical and molecular study of eight cases. 1450 91

Combined hepatocellular-cholangiocarcinoma is a rare form of primary liver cancer, featuring both hepatocellular and biliary epithelial differentiations. An intrahepatic tumor may be considered as a metastatic lesion. It has been suggested in the literature that the likelihood of metastasis in the cirrhotic liver is lower than that in the non-cirrhotic liver. A rare case of combined hepatocellular-cholangiocarcinoma and second primary colon adenocarcinoma in a 67-year-old male patient with liver cirrhosis is presented. Histologically, the intrahepatic mass was composed of a spindle cell sarcomatous component; a hepatocellular carcinoma component; and a cholangiocarcinoma component. There were focal transitional regions among the different components. Immunohistochemically, the cholangiocarcinoma component of the intrahepatic mass showed positive reactions for CK-7 but negative reactions for CK-20. The adenocarcinoma of the colon showed positive reactions for CK-20 but negative reactions for CK-7.
 ...
PMID:[A case of combined hepatocellular-cholangiocarcinoma with sarcomatous transformation and second primary colon cancer]. 1521 48


1 2 3 4 5 Next >>