Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that necrotic tumors retain their immunoreactivity for a range of cytokeratin antibodies. Some thyroid tumors undergo extensive necrosis after fine-needle aspiration (FNA) procedures. We evaluated the sensitivity of antibodies on necrotic thyroid tumors by examining a series of thyroid tumors consisting of 10 Hurthle cell neoplasms, 8 carcinomas, and 2 follicular adenomas (12 with post-FNA necrosis). These were stained with antibodies to AE1/3, PANCK, thyroglobulin and S100. Four of the cases of papillary carcinoma were also stained with antibodies to CK19. As a control for the specificity of thyroglobulin immunoreactivity in necrotic tissue, we also stained 11 nonthyroid tumors with extensive necrosis (7 carcinomas, 1 lymphoma, 2 melanomas, 1 sarcoma) for thyroglobulin. Six of 8 thyroid carcinomas were positive for AE1/3 and PANCK; AE1/3 reactivity was retained in necrotic areas of 4 of 6. AE 1/3 was positive in necrotic portions of 5 of 10 Hurthle cell lesions, whereas PANCKwas negative in all but 1. Thyroglobulin reactivity was present in 18 of 20 cases, and was preserved in necrotic portions of 5 of 6 carcinomas, as well as 8 of 10 Hurthle cell neoplasms. S100 cytoplasmic reactivity was present in 4 Hurthle cell neoplasms and 1 papillary carcinoma; this staining was lost in necrotic areas. No staining by thyroglobulin was observed in the viable or necrotic areas of nonthyroid neoplasms. The preservation of cytokeratin reactivity, measured by AE1/3, in thyroid neoplasms is a diagnostically useful feature in spontaneous and post-FNA infarction. PANCK is not a well-preserved marker in necrotic thyroid tissue. This difference may be due to detection of keratin 19 by AE1/3. Thyroglobulin is preserved in some necrotic thyroid carcinomas and in Hurthle cell lesions. Preservation of thyroglobulin reactivity in necrotic tissue is specific in that no staining was observed in nonthyroid neoplasms. These results suggest that thyroglobulin is useful in demonstrating thyroid lineage of both primary and metastatic necrotic tumor masses.
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PMID:Utility of immunohistochemistry in the evaluation of necrotic thyroid tumors. 1057 20

Furan cholangiocarcinogenesis in rat liver is proving to be a unique and useful animal model for investigating important aspects of the cellular and molecular pathogenesis of cholangiocarcinoma potentially relevant to the human disease. We now describe the first culture model of rat cholangiocarcinoma cells derived from a transplantable cholangiocarcinoma originally induced in the liver of a furan-treated rat. An epithelial cell isolate highly enriched in viable cholangiocarcinoma cells was consistently obtained from transplantable cholangiocarcinoma tissue utilizing a similar procedure to that recently developed by us to establish a new rat hyperplastic bile ductular epithelial cell culture model characterized by the appearance of polarized bile ducts in vitro. Primary cholangiocarcinoma cell cultures could be readily established with these isolated cells and, in addition, we established from one such culture a novel rat cholangiocarcinoma cell line designated C611B. Cultured C611B cholangiocarcinoma cells retained a number of important characteristic features of the carcinoma cells of the parent tumor, including marked expression of the tyrosine kinase growth factor receptor proteins c-Met and c-Neu. Under basal culture conditions, the C611B cell line exhibited a cell doubling time of approximately 24 h and was aneuploid, with a predominant chromosomal count of 43. Moreover, C611B cells on collagen gels were 100% tumorigenic when transplanted into inguinal fat pads of syngeneic rats. All tumors formed at the transplantation site were cytokeratin 19-positive, mucin-producing tubular adenocarcinomas whose histological and phenotypic features closely resembled those of the furan-induced parent transplantable rat cholangiocarcinoma. Based on our findings, we believe that this novel rat cholangiocarcinoma cell culture model can serve as a valuable resource for investigating aberrant growth properties and tumor progression in biliary cancer.
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PMID:Establishment of a novel rat cholangiocarcinoma cell culture model. 1059 Feb 29

Immunocytochemistry has indicated that, in the liver, the bcl-2 gene is generally expressed in bile duct cells and tumors of biliary origin. Both in situ hybridization and immunocytochemistry were used to analyze the expression of bcl-2 messenger RNA (mRNA) and its protein product (Bcl-2) in the tissue of 50 pure primary liver tumor (PLT) specimens including 40 hepatocellular carcinoma (HCC) specimens and 10 cholangiocellular carcinoma (CC) specimens. The phenotype of the tumors expressing bcl-2 was confirmed by immunocytochemical assessment of the cytokeratin (CK) profile (CK8, CK18, CK7, and CK19). Whereas positive immunoreaction with the anti-Bcl-2 MoAb was revealed in only 8 (20%) of 40 HCC specimens and 1 (10%) of 10 CC specimens, high contents of bcl-2 mRNA were found in 26 (65%) of 40 HCC specimens and 9 (90%) of 10 CC specimens. Regarding the CK profile, only 25 (62%) of 40 HCC specimens showed pure hepatocytic lineage (CKs 8-18), whereas among the remaining 15 HCC specimens, positivity for either CK7 (12 specimens) or CK19 (5 specimens) was observed. All 10 CC specimens stained with CKs 8-18-19, and 8 of 10 stained with CK 7 as well. These results indicate that PLTs display a greater expression of bcl-2 mRNA than of the Bcl-2 protein. Furthermore, CK profile assessment confirmed that bcl-2 expression is not confined to liver tumors of biliary origin. In the absence of a well-demonstrated post-transcriptional control of the gene, the authors propose the detection of bcl-2 mRNA by in situ hybridization as a possible alternative method for assessing the expression of bcl-2 mRNA in PLT.
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PMID:High levels of BCL-2 messenger RNA detected by in situ hybridization in human hepatocellular and cholangiocellular carcinomas. 1061 75

We describe herein a case of a mixed ductal-endocrine pancreatic carcinoma. Rare cases of mixed pancreatic tumors have been described, with endocrine and exocrine components each making up a significant proportion of the neoplasm; to our knowledge, only one case has been reported with a mixed liver metastasis. In our case, ductal and endocrine cells were intimately admixed in the primary tumor and in a peripancreatic lymph node metastasis, diagnosed by standard light microscopy and double immunostaining for cytokeratin 19 and synaptophysin. The endocrine component was immunoreactive for somatostatin. Tumors with admixed endocrine and exocrine components support the hypothesis of a common endodermal histogenesis for the ductal and endocrine cells in the human pancreas.
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PMID:Mixed ductal-endocrine carcinoma of the pancreas: a possible pathogenic mechanism for arrhythmogenic right ventricular cardiomyopathy. 1065 40

Exposure of cells derived from human mammary carcinoma cell line, MaTu, to daunorubicin started a selection process which reproducibly gave rise to sublines with different phenotypes. One subline exhibited a fibroblast-like morphology (MaTu/c7), while others retained the epitheloid phenotype of the parental cells (MaTu/p). Among the latter was clone 8 (MaTu/c8) which displayed piling-up structures not seen in MaTu/p cells. Striking differences were detected on immunocytochemistry using the anti-cytokeratin 19 antibody A53-B/A2 which positively reacted with cells from MaTu/c7, but not with those of MaTu/c8 and MaTu/p. In contrast, the anti-blood group H 2 antibody A46-B/B10 positively stained cells from MaTu/c8 and MaTu/p, but not those of MaTu/c7. Assays for tumorigenicity in nude mice demonstrated that MaTu/c7 is far less tumorigenic than MaTu/p, while MaTu/c8 showed a pattern distinguishing it from MaTu/p cells. Cross-resistance assays showed decreasing drug resistance in the order MaTu/c8 > MaTu/c7 > MaTu/p. These data suggest drug-induced differentiation with reversion of the neoplastic phenotype in MaTu/c7 and some form of malignant progression in MaTu/c8. This model system may be helpful for understanding cancer development, especially its relation to differentiation.
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PMID:Reverse transformation of human mammary carcinoma cells. 1069 20

The aim of this study was to analyze plasma DNA from primary and metastatic breast cancer cases for tumor-specific alterations and to compare these findings with immunocytochemistry and estimation of cytokeratin 19 (CK19) mRNA for detection of micrometastases. DNA was extracted from plasma, lymphocytes, and microdissected tumor tissue sections obtained from 71 patients with breast cancer and 9 controls. DNA samples were analyzed for loss of heterozygosity (LOH) and/or microsatellite instability (MI) by PCR with two polymorphic markers (DM-1 and D16S400). Reverse transcription-quantitative PCR (QPCR) and immunocytochemistry were used for detection of CK19 mRNA and protein. Breast cancer plasma DNA displayed frequent LOH (31.3%) and MI (11.6%) supported by the same alteration in microdissected tumor DNA. Most notably, 10 of the 39 patients with primary breast cancer showed LOH (n = 6) or MI (n = 4). We compared plasma tumor DNA, plasma and bone marrow QPCR, and blood and bone marrow immunocytochemistry in 32 of the patients with primary cancer. Of these, only one patient had immunocytochemically detectable carcinoma cells in the blood, and three showed abnormally high levels of plasma CK19 mRNA. All four of these patients had plasma DNA alterations. We then compared bone marrow findings: of the 10 primary breast cancers that showed LOH or MI, 6 had elevated CK19 mRNA and 5 had immunocytochemically positive cells. Tumor DNA is readily detectable in plasma of primary and metastatic breast cancer patients, and plasma DNA alterations (LOH and MI) reflect those seen in the tumor. The application of microsatellite analyses to plasma DNA may be useful in assessing tumor burden in breast cancer patients, particularly when combined with QPCR, and is preferable for patients with breast cancer, for whom sequential bone marrow aspiration is undesirable.
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PMID:Microsatellite alterations plasma DNA of primary breast cancer patients. 1074 42

Based on the important role of CD44 splice variants in colorectal cancer progression and metastasis, we evaluated the use of CD44v6 expression to detect and assess the metastatic potential of colorectal tumour cells circulating in peripheral blood. A nested amplification was designed that allowed to detect 10-100 colon cancer cells. This assay was applied to blood samples from healthy donors. Strong signals were detected in all cases, indicating that it cannot be used to detect colorectal carcinoma cells in whole blood. We then included an enrichment step based on the use of an anti-epithelial cells monoclonal antibody (BerEP4) coupled to magnetic beads. The CD44v6 reverse transcription polymerase chain reaction (RT PCR) assay was performed on cDNA synthesized from blood samples treated with these beads. We analysed 18 samples from 12 patients with a gastrointestinal disease, and 36 samples from ten patients with a colorectal cancer. None of the patients used as negative controls were found to contain epithelial cells in their blood as determined by cytokeratin 19 RT-PCR. By contrast, CD44 transcripts containing exon v6 were detected in nine out of the 18 samples tested (50%). For the colorectal cancer patients, six out of the seven samples (85.7%) that were cytokeratin 19-positive were CD44v6-negative, whereas ten samples out of the 29 not containing epithelial cells were CD44v6-positive (34.5%). This is probably due to the persistence of CD8+ leucocytes in the enriched preparations, as determined by PCR analysis of the CD8 alpha-chain. We conclude that detection of CD44v6 transcripts using a sensitive nested RT-PCR assay has no potential value to detect and characterize colorectal cancer micrometastases from blood, even following an initial enrichment step.
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PMID:Limitations of CD44v6 amplification for the detection of tumour cells in the blood of colorectal cancer patients. 1075 2

The aim of this study was to evaluate the relationship between renal function and the blood level of some tumor markers that are low molecular weight proteins, that is, tumor-associated trypsin inhibitor (TATI), squamous cells carcinoma antigen (SCC), cytokeratin 19 fragments (CYFRA 21-1), tissue polypeptide antigen (TPA), and M3-specific epitope of tissue polypeptide antigen (TPS). In 41 adult patients without evidence of neoplastic disease, glomerular filtration rate (GFR) and the blood levels of creatinine and of the tumor markers were determined. The decrease in GFR was accompanied by an increase in serum levels of TATI, SCC, CYFRA 21-1, and TPA. The serum level of tumor markers increased particularly when GFR fell below 40 ml/min. On the basis of these results, the renal function must be taken into account for the clinical evaluation of the studied tumor markers.
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PMID:Renal function and serum concentration of five tumor markers (TATI, SCC, CYFRA 21-1, TPA, and TPS) in patients without evidence of neoplasia. 1075 27

Recently, cholangiocellular carcinoma (CCC) was successfully induced in the hamster by infecting with Clonorchis sinensis following hepatocarcinogen treatment and has been proposed as a suitable model to study the pathogenesis of human CCC. In this hamster model, oval cells are suggested to be cells of origin of CCC. More direct analysis of histogenesis of CCC would become possible if large numbers of highly purified oval cells of hamster origin are obtained. In this study, we describe successful isolation of highly purified oval cells from hamsters. Oval cells were induced by diethylnitrosamine and 2-acetylaminofluorene treatment under choline deficient diet and isolated by centrifugal elutriation method. This isolated cells were highly homogenous in size (10.9+/-1.1 microm in diameter) and had a high nuclear to cytoplasmic ratio, an oval-shaped nucleus and a few cytoplasmic organelles. Immunocytochemically, 85.4+/-1.6%, 75.1+/-2.0%, 62+/-1.5% and 25.6+/-2.7% of the isolated cells were positive for cytokeratin 19, OV-6, albumin and alpha-fetoprotein, respectively, indicating that these cells had phenotypic characteristics of both hepatocytes and bile duct epithelium. The isolated cells were therefore considered to be hamster oval cells.
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PMID:Isolation of liver oval cells from hamsters treated with diethylnitrosamine and 2-acetyl aminofluorene. 1077 May 96

The epidermal growth factor receptor (EGFR) is overexpressed in 50-70% of human primary breast, lung, and colon carcinomas, whereas it is not usually expressed in hematopoietic cells. We developed a novel reverse transcription-PCR (RT-PCR)-Southern blot assay for the detection of circulating, EGFR mRNA-expressing tumor cells in carcinoma patients. The assay was set up by increasing the amount of cDNA step by step in the PCR reaction. The highest sensitivity and specificity were found when using 800 ng of cDNA in the PCR reaction. Peripheral blood samples from 91 patients with either colon (38), lung (30), or breast (23) carcinomas and from 38 healthy volunteers were analyzed. EGFR transcripts were found in 44 of 75 (59%) patients with metastatic carcinoma and in 4 of 38 (10.5%) healthy donors (P < 0.001; chi2 test). The expression of EGFR, cytokeratin 19, and carcinoembryonic antigen mRNA in blood samples from patients with metastatic colon carcinoma was compared. EGFR, cytokeratin 19, and carcinoembryonic antigen transcripts were found in 8 of 11 (73%), 3 of 11 (27%), and 5 of 11 (45%) patients, respectively. Furthermore, two of seven (29%) Dukes' B and five of nine (55%) Dukes' C colon carcinoma patients were found to express EGFR mRNA in the peripheral blood. All patients that expressed EGFR transcripts in the peripheral blood were found to express the EGFR protein in the corresponding primary carcinoma, as assessed by immunohistochemistry. These data suggest that the EGFR assay that we developed is a highly specific and sensitive technique to detect circulating tumor cells in patients affected by different carcinoma types.
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PMID:Detection of circulating tumor cells in carcinoma patients by a novel epidermal growth factor receptor reverse transcription-PCR assay. 1077 75


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