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)

Parathyroid hormone-related peptide is the major factor responsible for hypercalcemia of malignancy. There is increasing evidence that parathyroid hormone-related peptide also plays an important role in the growth and differentiation of both neoplastic and non-neoplastic cells. Recently we found that reactive human bile ductules and cholangiocarcinomas, but not normal bile ducts, human hepatocytes nor hepatocellular carcinomas, express parathyroid hormone-related peptide and we speculated that parathyroid hormone-related peptide may function as a growth and differentiation factor for bile ductular epithelial cells. Using a specific polyclonal antibody for immunostaining and a digoxigenin-random prime-labeled probe for in situ hybridization assay, we found that only cell lines with a bile duct phenotype expressed parathyroid hormone-related peptide and its mRNA. HepG2 cells with hepatocellular phenotype (CK19-, CK7-, CK8+, CK18+, albumin+) do not express parathyroid hormone-related peptide. However, A16 (HepG2 derived cell line) expressing bile duct marker CK19, also expressed parathyroid hormone-related peptide, while hepatocyte markers CK8, CK18, CALLA and albumin were negative. In addition, the H1 cell line (adult human hepatocytes immortalized in our laboratory by SV40 DNA transfection, passaged at least 40 times and cultured for 13 months) expressed bile duct marker CK7 and parathyroid hormone-related peptide, while hepatocyte markers CK8, CK18, CALLA and albumin were negative. Previous studies demonstrated that parathyroid hormone-related peptide gene expression in keratinocytes can be modulated by serum, growth factors and cycloheximide although there is a species and cellular specificity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parathyroid hormone-related peptide is expressed and rapidly inducible in human liver cell cultures that have a bile duct phenotype. 749 87

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

Recent years have witnessed significant developments in the use of immunohistochemistry in diagnostic gynaecological pathology. This review details the most significant of these. In ovarian pathology, differential cytokeratin staining (CK7 and 20) assists in distinguishing between a primary ovarian adenocarcinoma and a metastatic adenocarcinoma, especially of colorectal origin. The development of markers characteristic of ovarian sex cord-stromal tumours (especially alpha-inhibin) facilitates diagnosis of these neoplasms which is often difficult by morphology alone due to the wide differential diagnosis. In the uterus, the distinction between a primary endometrial and endocervical adenocarcinoma may be facilitated by use of a small panel of antibodies, including CEA, ER and vimentin. Newly developed antibodies such as CD10 and h-caldesmon may be of use in the diagnosis of uterine mesenchymal lesions, especially in the distinction between endometrial stromal and smooth muscle lesions. Proliferation markers, such as MIB1, are of value in the cervix in the diagnosis of preinvasive squamous and glandular lesions. Recent studies have shown that cervical adenoma malignum exhibits a gastric phenotype. Advances have also been made in trophoblastic disease with the development of antibodies reactive against trophoblast such as alpha-inhibin, mel-Cam and p57. A newly developed monoclonal antibody HMGIC which is expressed in vulvovaginal aggressive angiomyxoma may prove to be of value in the often difficult distinction of this lesion from its histological mimics.
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PMID:Recent advances in immunohistochemistry in gynaecological pathology. 1194 15

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

To distinguish common epithelial tumors arising in the kidney may have significant implications, in terms of molecular ontogeny and prognosis. It is important to investigate the distribution of immunoexpression of commonly used markers among renal neoplasms and to develop a useful panel as an adjunct to histologic examination, which could lead to the accurate diagnosis of both primary and metastatic tumors. Immunohistochemical stains for CD10, vimentin (VIM), E-cadherin (E-CD), cytokeratins (CK) 7, 8, 19, and 20, high molecular weight keratin (HCK), and peanut lectin agglutinin (PL) (Arachis hypogaea) were performed on 45 (96 for CK7, CK20) conventional (CC), 20 papillary (PC), and 6 (24 for CK7, CK20) chromophobe renal carcinomas (CPC); 12 oncocytomas (OC); 5 collecting duct carcinomas (CDC), and 25 urothelial carcinomas of the renal pelvis (UC). Reactivity for CD10 was evaluated on the basis of the presence of cell surface staining; that for all CKs, cytoplasmic/membranous staining; and that for PL, luminal staining. Both CD10 and VIM were predominantly expressed in CC and PC; E-CD in CPC, OC, and UC; CK7 in PC, CPC, and UC; CK8 and CK19 in CDC and UC; CK20 in UC; HCK in CDC and UC; and PL in CDC. CC and OC were predominantly CK7-/CK20-; PC, CK7+/20-; CPC, CK7+/CK20- or CK7-/CK20-; and UC, CK7+/CK20- or CK7+/CK20+. CDC showed slight predominance of CK7-/20- over CK7+/CK20-. CC was most frequently CD10+/CK7-/HCK-/PL-; PC, CD10+/CK7+/HCK-/PL-; CPC, CD10-/CK7+/HCK-/PL-; OC, CD10-/CK7-/HCK-/ PL-; CDC, CD10-/CK7+/HCK-/PL+ or CD10-/CK7-/ HCK+/PL+; and UC, CD10-/CK7+/HCK+/PL-. Discriminant analysis suggested that CD10/CK7/HCK/PL may be a useful primary immunopanel for distinguishing among CC, PC, CDC, and UC.
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PMID:Immunohistochemical profile of common epithelial neoplasms arising in the kidney. 1261 43

The diagnosis of primary clear cell carcinoma of the ovary or kidney is usually straightforward. However, problems in ascertaining the site of the primary tumor may arise when there is widespread metastatic disease or when clear cell carcinoma is present in both the ovary and kidney. In this study, the value of a panel of antibodies in distinguishing between an ovarian and renal clear cell carcinoma was evaluated. The panel comprised cytokeratin (CK)7 and 20, vimentin, estrogen receptor (ER), CD10, and renal cell carcinoma (RCC) marker. Ovarian clear cell carcinomas (n=14) were positive with CK7 (14/14), vimentin (6/14), ER (2/14), and RCC marker (2/14). All were negative with CD10 and CK20. Renal clear cell carcinomas (n=14) were positive with CD10 (14/14), RCC marker (14/14), vimentin (7/14), CK7 (2/14), and CK20 (1/14). All were negative with ER. This panel allows clear cell carcinomas of the ovary and kidney to be distinguished with a high degree of certainty and is a useful adjunct to histologic examination. Primary ovarian clear cell carcinomas are characterized by CK7 positivity, whereas primary renal neoplasms are characterized by positivity for CD10 and RCC marker and negative staining with CK7.
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PMID:A panel of immunohistochemical stains assists in the distinction between ovarian and renal clear cell carcinoma. 1281 95

Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are unusual neoplasms with histologic features that resemble those within ovarian Sertoli and granulosa cell tumors. We report the case of a 24-year-old woman with a UTROSCT presenting as a cervical mass, which on initial evaluation was thought to represent cervical adenocarcinoma. The patient's cervical biopsy specimen contained epithelioid cells arranged in tubules and anastomosing cords, without significant cellular atypia or mitotic activity. Because this morphology elicited a broad differential diagnosis, immunohistochemical studies were performed. The tumor was found to be diffusely positive for cytokeratin cocktail, calretinin, and desmin, focally positive for CK7 and SMA, and negative for EMA, CEA, inhibin, CD10, CK20, chromogranin, and synaptophysin. Ultrastructural examination revealed occasional gland-like lumens with cells joined by desmosomes and a continuous basal lamina. UTROSCTs have features that may cause them to be confused with more common tumors, especially in limited biopsy samples, and should be included in the differential diagnosis when a gland-forming neoplasm with an unusual appearance is identified in a cervical or endometrial biopsy specimen.
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PMID:Uterine tumor resembling ovarian sex-cord tumor: report of a case mimicking cervical adenocarcinoma. 1281

We present a case of benign mixed tumor of the vagina with its typical clinicopathologic and expanded immunohistochemical features. The strong coexpression of the mesenchymal spindle cell component with epithelial markers such as CK7, together with strong CD10, Bcl2, and estrogen and progesterone receptors favors a mullerian derived tumor. The tumor is best labeled as benign mixed mullerian tumor as originally designated.
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PMID:Benign mixed tumor of the vagina: case report with expanded immunohistochemical profile. 1291 36

Mammary small cell carcinoma (SmCC) is a very rare neoplasm with a poor prognosis compared with other invasive carcinomas. We studied the histological and immunohistochemical profiles of two cases of mammary SmCC, and compared them with those of five cases of carcinoma with endocrine features (CEF) and five cases of invasive ductal carcinoma (IDC), to elucidate the correct diagnosis of mammary SmCC. Immunohistochemical analysis was performed with antibodies against cytokeratins (CKAE1/AE3, CK34betaE12, CKCAM5.2, CK7, CK8, CK19, CK20), epithelial membrane antigen (EMA), vimentin, CD10, neural cell adhesion molecule (NCAM; CD56), neuron-specific enolase (NSE), chromogranin A, S-100 protein, carcino-embryonic antigen (CEA), E-cadherin, N-cadherin, thyroid transcription factor-1 (TTF-1), p53, estrogen (ER), progesterone (PR), HER2/neu, bcl-2, synaptophysin, calcitonin and Leu7. SmCCs were diffusely and strongly positive for NCAM in comparison with CEFs and IDCs. SmCCs were negative for vimentin, whereas CEFs and IDCs were positive. Neuro-endocrine carcinomas, including SmCCs and CEFs, were diffusely and strongly positive for NSE, compared with IDCs. Moreover, neuroendocrine carcinomas were negative for CK34betaE12, CK20 and CD10, whereas IDCs were positive. Our study suggests that NCAM and vimentin are useful markers for the diagnosis of mammary SmCC. CK34betaE12, NSE, CD10, CK20 and chromogranin A appear to be useful for differentiating neuroendocrine carcinoma from IDCs.
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PMID:Comparative study of primary mammary small cell carcinoma, carcinoma with endocrine features and invasive ductal carcinoma. 1501 Aug 80


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