Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

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

We report a case of a retiform Sertoli-Leydig cell tumor of intermediate differentiation presenting as a uterine intracavity polypoid mass in a 63-year-old woman. In contrast to sertoliform endometrioid carcinoma and to hitherto reported uterine tumors resembling ovarian sex cord tumors (UTROSCTs), which are primarily characterized by tubular glands and solid tubules, this tumor, which most likely represents a UTROSCT, showed a large spectrum of histologic features typical of a genuine retiform Sertoli-Leydig cell tumor. The diagnosis was confirmed by a battery of immunohistochemical stains, which also served as a tool for differential diagnosis with other neoplasms. The tumor cells were positive for broad spectrum keratin (CK) CK18, vimentin, calretinin, and progesterone receptor. Only a few isolated cells stained for inhibin. The tumor cells were negative for CK7, CK5/6, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), thrombomodulin, 013 (CD99), melan A, alpha-fetoprotein (AFP), placental alkaline phosphatase (PLAP), alpha-1-antitrypsin, estrogen receptor, S100, neurone specific enolase (NSE), chromogranin, synaptophysin, desmin, caldesmon, and CD10. Divergent differentiation of uterine cells seems to be the most likely pathogenetic mechanism. To the best of our knowledge, no UTROSCT showing such a variety of histologic features indicative of a true sex cord tumor has been reported before.
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PMID:Uterine retiform sertoli-leydig cell tumor: report of a case providing additional evidence that uterine tumors resembling ovarian sex cord tumors have a histologic and immunohistochemical phenotype of genuine sex cord tumors. 1617 78

The differential diagnoses of hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and adrenocortical carcinoma (ACC) are sometimes difficult due to their overlapping histologic features. Immunohistochemistry is a helpful adjunct in supporting the histologic diagnosis. In this study, the authors used the tissue array technique to systemically analyze the efficacy of different immunohistochemical panels in discerning these neoplasms. Immunohistochemical stains were performed on a total of 895 tumors (including 170 HCCs, 176 RCCs, and 40 ACCs) using monoclonal antibodies against hepatocyte antigen (HPA), CD10, RCC marker, vimentin, alpha-inhibin, keratins (KL-1, CAM 5.2, 7, and 20), epithelial membrane antigen, and polyclonal antibodies against carcinoembryonic antigen (pCEA) and alpha-fetoprotein, and antibodies Melan-A (A103), MOC31, and BG8. HPA immunostain alone detected 85.9% of HCCs, and the addition of canalicular pattern of pCEA and CD10 immunostains raised the sensitivity to 94.7%. RCC marker was positive in 54.5% of RCCs but was negative in all non-RCC tumors. Using positive CD10 and negative HPA and pCEA together with RCC marker increased the sensitivity to 74.4%. Immunoreactivity for alpha-inhibin and A103 could be detected in 67.5% and 55% of ACCs, respectively. When the two antibodies were combined, 82.5% of ACCs were labeled. Proper selection of immunohistochemical stains aid in the differential diagnosis of the three neoplasms. Using the tissue array technique, the authors also showed an effective model for comprehensive antibody testing.
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PMID:Differential immunoprofiles of hepatocellular carcinoma, renal cell carcinoma, and adrenocortical carcinoma: a systemic immunohistochemical survey using tissue array technique. 1628 Jun 64

Intrahepatic cholangiocarcinomas are second most common primary tumors of the liver. They are usually seen in 6th to 7th decades of life and at an advanced stage leading to poor prognosis. Their occurrence in the young age group is rare. Histopathological features of this tumor are well documented but literature regarding cytomorphological features on FNA is limited. We describe the cytological features of this tumor in a young woman presenting primarily with a rib metastasis. FNA smears from hard lump in the right chest wall and liver mass showed small round tumor cells arranged in the form of sheets, clusters and occasional tubules. The cells showed mild pleomorphism and bland nuclear morphology. Intimately admixed with tumor cells were spindle shaped fibroblastic cells. Serum alpha-fetoprotein level was within normal limit. Special stain for bile and immunocytochemical staining for NSE, chromogranin and CALLA were all negative. Cholangiocarcinoma was diagnosed based on cytological findings and special stains and this diagnosis was histologically confirmed on biopsy.
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PMID:Cytological diagnosis of cholangiocarcinoma with rib metastasis in a young female--a case report. 1629 44

Hepatocellular carcinoma (HCC) is known for its histomorphologic heterogeneity. Immunohistochemistry (IHC) can help in the comparative morphologic evaluation of HCC, its variants and their mimics. Some of these diagnostic challenges can be attributed to (i) the variety of neoplasms that can arise from the hepatic stem cell lineage; (ii) the spectrum of well-differentiated hepatocellular nodular lesions; (iii) the liver being a target for metastases with some of these histologic entities mimicking variants of HCC or actually arising in the liver; and (iv) the limitations of serum alpha-fetoprotein (AFP). The role of IHC is in the distinction of benign hepatocellular nodules from reactive hepatocytes; WD-HCC from benign hepatocellular nodules; poorly differentiated HCC from cholangiocarcinoma and metastases; and determination of histogenesis of malignant tumor; and of primary site of origin of malignant tumor. A panel of antibodies has more discriminant value. AFP expression usually indicates malignancy in a hepatocellular nodule and hepatocytic histogenesis of a malignancy. Polyclonal carcinoembryonic antigen (pCEA) and CD10 stain bile canaliculi in better-differentiated HCC. HepPar1 is generally accepted as a hepatocytic marker. However, not all HCC stain uniformly and not all HepPar1-positive tumors are of hepatocytic origin or arise in the liver. Mature hepatocytes and hepatocellular nodules stain with CAM 5.2, CK 8, and 18 but not with CK 7, 19, 20, or AE1/AE3. Biliary epithelium expresses CK 7 and 19. CD 34 highlights sinusoidal capillarization. AFP, pCEA/CD10, and CD34 are useful for ascertainment of malignancy in hepatocellular nodules; HepPar1 and cytokeratins to be included if histogenesis is the issue. IHC results should be interpreted in the larger context of the case.
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PMID:Diagnostic utility of immunohistochemistry in hepatocellular carcinoma, its variants and their mimics. 1693 16

Hepatocellular carcinoma (HCC) may present in various ways, but only very rarely with symptoms of distant metastases or evolve from ectopic liver tissue. This report describes a case of a 62-year-old white man who was admitted for hemoptysis and a large left chest wall mass that was growing for about a year. The patient underwent Fine-needle aspiration (FNA) of the mass that revealed poorly differentiated large-cell carcinoma. A lung primary was suspected initially; however, further workup of this patient showed an elevated serum alpha-fetoprotein (AFP) level of 16,425 ng/ml. A computerized tomography (CT) scan of the abdomen showed cirrhotic liver, evidence of esophageal varices, but no evidence of a liver mass. The FNA findings were reviewed and ancillary studies were performed, including pan cytokeratin (AE1/3), Hepatocyte Paraffin 1 (HepPar-1), AFP, CD10, CD34, and polyclonal CEA. The results confirmed the diagnoses of HCC probably from occult primary or from ectopic liver tissue. The former was suggested, since serum AFP was dropped to 6,640 ng/ml following resection of the tumor. We concluded that HCC should be considered in the list of differential diagnosis of chest wall mass. HCC may present as metastatic disease from a clinically and radiologically unrecognized liver mass. FNA, coupled with ancillary studies, provides a rapid and accurate diagnostic tool in challenging cases.
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PMID:Cytomorphology of a solitary left chest wall mass: an unusual presentation from unknown primary hepatocellular carcinoma. 1770 51

Endometriosis is a frequent benign gynecological disease; nonetheless, it can demonstrate some aspects that resemble malignant disease. Malignant transformation of endometriosis occurs mainly in the ovary. A rare case of transition between typical endometriosis and clear cell carcinoma with immunohistochemical study is presented. The patient, a 30-year-old Caucasian woman (para 0), was diagnosed with endometriosis ten years before. Six months later she developed a left cystic ovarian tumor (58 cm3) that persisted after two ultrasounds in a four-month period. Tumor markers were normal (CA125, CA 15.3, CA 19.9, alpha-fetoprotein, carcinoembrionary antigen A1). There was no ascites. The left ovarian mass was removed by laparotomy and endometriosis in continuity with carcinoma positive for cytokeratin 7 and estrogen receptor was revealed. CD10 was positive in the stromal cells of the endometriosis. Clear cell carcinoma grade 3 was diagnosed. In conclusion, although a rare event, the association of typical endometriosis and clear cell carcinoma of the ovary should be kept in mind, mainly in patients with a persistent ovarian cyst.
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PMID:Ovarian clear cell carcinoma associated with endometriosis: a case report with immunohistochemical study. 1796 22


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