Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fresh, superficial transitional cell carcinomas (TCCs) of low-grade atypia (3 grade I, Ta; 6 grade II, Ta), as well as primary cultures derived from them were labeled with [35S]methionine for 16 h, between 2 and 6 days after inoculation. Whole protein extracts were subjected to IEF (isoelectric focusing) two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) followed by autoradiography. Proteins were identified by a combination of proteomic technologies that included microsequencing, mass spectrometry, 2-D PAGE immunoblotting and comparison with the bladder TCC protein database available on the internet (http://biobase.dk/cgi-bin/celis). Comparison of the IEF 2-D gel protein profiles of fresh tumors and their primary cultures showed that the overall expression profiles were strikingly similar, although differing significantly in the levels of several proteins whose rate of synthesis was differentially regulated in at least 85% of the tumor/culture pairs as a result of the short-term culturing. Most of the proteins affected by culturing were upregulated and among them we identified components of the cytoskeleton (keratin 18, gelsolin and tropomyosin 3), a molecular chaperone (hsp 28), aldose reductase, GST pi, metastasin, synuclein, the calreticulin precursor and three polypeptides of unknown identity. Only four major proteins were downregulated, and these included two fatty acid-binding proteins (FABP:FABP5 and A-FABP) which are thought to play a role in growth control, the differentiation-associated keratin 20, and the calcium-binding protein annexin V. Proteins that were differentially regulated in only some of the cultured tumors included alpha-enolase, triosphosphate isomerase, members of the 14-3-3 family, hnRNPs F and H, PGDH, hsp (heat-shock protein) 60, BIP, the interleukin-1 receptor antagonist, the nucleolar protein B23, as well as several proteins of yet unknown identity. The suitability of in vitro bladder tumor culture models to study complex biological phenomena such as malignancy and invasion is discussed.
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PMID:Short-term culturing of low-grade superficial bladder transitional cell carcinomas leads to changes in the expression levels of several proteins involved in key cellular activities. 1019 43

Adenoid cystic carcinomas (ACCs) and adenoid basal carcinomas (ABCs) are rare neoplasms of the uterine cervix that are currently regarded as distinct clinicopathologic entities. Accurate distinction between ABCs and ACCs is of clinical importance because of differences in their biological behavior. This study compares the morphologic, mucin, and immunohistochemical profiles of 18 cervical ACCs, 8 ABCs, and 1 combined ABC-ACC. Serial sections from the 27 cases were stained with hematoxylin and eosin, periodic acid-Schiff-diastase, mucicarmine, and alcian blue and subjected to a panel of immunoperoxidase markers, namely, MNF116, CAM 5.2, CK7, CK20, epithelial membrane antigen, carcinoembryonic antigen (CEA), S-100, HHF 35, laminin, and type IV collagen. One ACC was also examined ultrastructurally. Almost all patients were postmenopausal black women. The distinction between ABC and ACC was best made morphologically. Divergent epithelial differentiation was seen in 18 cases (11 ACCs, 6 ABCs, and 1 ABC-ACC). Six cases with intact surface epithelium showed a high grade squamous intraepithelial lesion. There was no significant difference in mucin staining. Both tumor types had a similar immunohistochemical profile, apart from type IV collagen and laminin staining, which occurred exclusively in relation to the extracellular basement membranelike material in the ACC. Eleven ACCs and three ABCs were S-100-positive, including the respective ACC and ABC components of the combined ABC-ACC. Eight of the S-100-positive neoplasms with ACC morphology also stained with HHF 35, suggesting myoepithelial differentiation. The latter was confirmed in one ACC examined ultrastructurally. The similar clinical profiles, apart from the different biological behavior, capacity for divergent differentiation, and the occurrence of ABC areas in some ACCs and vice versa suggest that these tumors may share a common histogenesis, forming part of a morphologic and biologic spectrum of basaloid cervical neoplasms of putative "reserve cell" origin. Circumstantial evidence suggests that ABC may be a precursor of cervical ACC.
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PMID:Adenoid cystic and adenoid basal carcinoma of the uterine cervix: comparative morphologic, mucin, and immunohistochemical profile of two rare neoplasms of putative 'reserve cell' origin. 1019 75

Although rare, renal cell carcinoma (RCC) can metastasize to the bladder. When this occurs, it might complicate diagnosis. Morphologically, RCC can be confused with transitional cell carcinomas (TCCs), especially those exhibiting clear cell features, and also with other bladder tumors, such as paragangliomas and metastatic melanomas. We report seven cases of RCC metastatic to the bladder that occurred in 6 men and 1 woman who were 35 to 69 years old. The most common presenting symptom was the reappearance of hematuria, which developed from 2 to 131 months (mean, 41.3 mo) after the removal of the primary RCC. In all of the patients, the metastatic RCC involved multiple organs; no case had an isolated metastasis to the bladder. The prognosis was poor, and five patients died of disease between 4 and 24 months (mean, 12.8 mo) after diagnosis of the metastasis to the bladder. The remaining two patients were lost to follow-up. All of the tumors were conventional clear or "granular" cell RCCs, with nuclear grades of 2 or 3. In five patients, metastases were confined to the lamina propria, but in two patients, tumors involved the muscularis propria as well. A comparative immunohistochemical study showed that metastatic RCCs were positive for CAM5.2, vimentin, and Leu-M1, and negative for cytokeratin 20, cytokeratin 7, 34betaE12, carcinoembryonic antigen, S-100 protein, HMB45, and chromogranin. Classic and clear cell TCCs were positive for all of the cytokeratins and carcinoembryonic antigen and negative for vimentin. Paragangliomas were positive for chromogranin and showed scattered positivity for the S-100 protein in the sustentacular cells. Metastatic melanomas were positive for S-100 protein and HMB45. The histologic appearance of RCC, particularly the delicate fibrovascular stroma with abundant sinusoidal vessels, is a feature that can be used to recognize the tumor. When there is difficulty diagnosing metastatic RCC, TCC, or other tumors in the bladder, the immunohistochemical findings can assist in the differential diagnosis.
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PMID:Metastatic renal cell carcinoma to the bladder: a clinicopathologic and immunohistochemical study. 1022 98

Dimethylbenzanthracene (DMBA) induces pancreatic adenocarcinomas in rats 9 months after carcinogen exposure, with precursor lesions (tubular complexes) developing 1 month after initiation of treatment. Because previous studies have suggested an acinar cell of origin for these tumors, we investigated the expression pattern of ductal, acinar, and islet cell markers in these cancers to gain insight into their phenotype and cell of origin. Pancreatic neoplasms were induced in rats by implantation of DMBA into the head of the pancreas. Lesions studied included 10 early tubular complexes (DMBA for 2 weeks), 8 tubular complexes (DMBA for 1 month), and 10 adenocarcinomas (DMBA for 9 months). Normal rat pancreas served as a control. For comparison, 5 human ductal adenocarcinomas were also evaluated. Immunohistochemistry with ductal (keratin, cytokeratin 19, cytokeratin 20), acinar (chymotrypsin), and islet (chromogranin A) cell markers was performed to analyze the tissues. Rat tubular complexes and adenocarcinomas revealed strong expression of keratin, cytokeratin 19, and cytokeratin 20 in the cytoplasm of all neoplastic cells, absence of chymotrypsin, and rare immunoreactivity to chromogranin A. Human adenocarcinomas showed strong expression of keratin and cytokeratin 19 in all neoplastic cells, expression of cytokeratin 20 in 5-20% of cells, and absence of chymotrypsin and chromogranin A. Pancreatic adenocarcinomas induced by DMBA in rats express markers consistent with a ductal phenotype, as observed in human tumors. Ductal marker expression in early tumor stages suggests a ductal cell of origin.
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PMID:Immunohistochemical characterization of pancreatic tumors induced by dimethylbenzanthracene in rats. 1023 60

Cutaneous lymphadenoma is an uncommon basaloid epithelial tumor of uncertain histogenesis, most recently classified as a variant of trichoblastoma. Because characteristic immunohistochemical findings have been reported in trichoblastomas, we evaluated the staining patterns of five cutaneous lymphadenomas and compared the results to those of ten trichoblastomas and ten nodular basal cell carcinomas (BCCs), using antibodies to cytokeratin 20 (CK20), bcl-2, and CD34. In addition, because lymphadenomas contain intraepithelial S100-positive putative Langerhans cells, we compared staining of all tumor groups for S100 protein and CD1a. We also attempted to corroborate recent reports of CD30-positive activated lymphocytes in lymphadenomas. We identified CK20-positive Merkel cells in 3/5 lymphadenomas, 7/10 trichoblastomas, and none of the BCCs. Staining for bcl-2 accentuated the peripheral epithelial layer in all lymphadenomas and in 3/10 trichoblastomas, while the remaining trichoblastomas and all BCCs stained diffusely. There was stromal staining with CD34 in two lymphadenoma, 4 trichoblastomas, and 3 BCCs. All lymphadenomas featured numerous intraepithelial S100-positive cells which were also positive for CD1a in three cases tested. In addition, 8/10 trichoblastomas and 2/10 BCCs contained modest numbers of cells labelling for S100 and CD1a. Two of three lymphadenomas contained rare single cells resembling histiocytes faintly positive for CD30, and similar cells labelled for CD68. We conclude that the similar staining patterns of lymphadenomas and trichoblastomas support the classification of lymphadenoma as a variant of trichoblastoma. Staining with CD34 does not reliably distinguish between these tumors and BCCs. Lymphadenomas, trichoblastomas, and BCCs may all contain Langerhans' cells. The relationship between these cells and the striking lymphoid infiltrates seen in lymphadenomas is not clear. In our cases, the CD30-positive cells in lymphadenomas appear to represent histiocytes rather than activated lymphocytes.
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PMID:Immunohistochemical comparison of cutaneous lymphadenoma, trichoblastoma, and basal cell carcinoma: support for classification of lymphadenoma as a variant of trichoblastoma. 1023 76

Four children who developed oncocytoid renal cell carcinoma (RCC) after neuroblastoma are reported. One patient had multiple, bilateral RCCs. The mean age at time of diagnosis of RCC was 8.8 years (range, 5-13 years). The mean interval between neuroblastoma and RCC was 7.15 years (range, 3.1-11.5 years). The histologic findings of these RCCs did not fit within the spectrum of known renal epithelial neoplasms. Most of the neoplastic cells in all cases had eosinophilic, oncocytoid cytoplasm and were arranged in solid and papillary growth patterns. A subset of cells with reticular cytoplasm was also present. Immunohistochemical studies demonstrated keratins 8 and 18 in all neoplasms and keratin 20 in two cases. DNA ploidy analysis revealed that two of three neoplasms assessed were aneuploid. Cytogenetic studies revealed 45, XX, add or dup (7)(q32q36) in one neoplasm, and 83-89, XXXX, -1 ,-3, del (3)(q11.1q2?1), der(4)t(4;?22) (q32;q11.2), -14, -22 in a second tumor. Microsatellite polymerase chain reaction analysis detected no abnormalities in one neoplasm and allelic imbalance of chromosomes 2p31-32.2, 8p22, 9p22-24, 13q22, 20q13, and 22q11 in a second tumor. In case 4, two different RCCs excised 6 months apart were analyzed. The initial neoplasm showed allelic imbalance of chromosomes 2q31-32.2, 5q22, 5q31, 10p13-14, 13q22, 14q31, and 20q13. The subsequent neoplasm showed allelic imbalance of chromosomes 3p21.3, 14q31, and 20q13. The common presence of 14q31 and 20q13 abnormalities suggests that these two neoplasms were genetically related. In aggregate, these findings are distinctive, are not found in known types of RCC, and support the morphologic impression that oncocytoid RCC after neuroblastoma is a distinct clinicopathologic entity.
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PMID:Oncocytoid renal cell carcinoma after neuroblastoma: a report of four cases of a distinct clinicopathologic entity. 1040 99

Wolffian adnexal tumor (WAT) is a rare neoplasm believed to originate from wolffian remnants on the basis of its location in areas where these remnants are abundant. To study its histogenesis, the immunoprofile of 25 WATs was compared with that of 10 cervical and vaginal mesonephric remnants and 12 rete ovarii. WATs were unilaterally located in the broad ligament (n = 10), mesosalpinx (n = 9), ovarian hilus (n = 5), and pelvis, not otherwise specified (n = 1). They showed varying morphologies with solid (spindle cells), tubular (lined by columnar cells), retiform and multicystic (spaces lined by cuboidal and attenuated cells) patterns. WATs were immunoreactive for pan-cytokeratin (AE1/3, CK1) (100%), CAM 5.2 (100%), cytokeratin 7 (CK7) (88%, focal staining), keratin 903 (17%), epithelial membrane antigen (EMA) (12%), estrogen receptor (28%), progesterone receptor (24%), androgen receptor (78%), inhibin (68%), calretinin (91%), and vimentin (100%). No immunostaining was detected with monoclonal carcinoembryonic antigen and cytokeratin 20. The pattern of staining was nearly identical to that of the rete ovarii and differed somewhat from mesonephric remnants, which were diffusely immunoreactive for CK7, immunopositive for EMA (apical staining), and nonreactive for inhibin. Our findings provide immunohistochemical support for the derivation of WATs from wolffian remnants, in particular from the rete ovarii. Because of immunoreactivity for inhibin and calretinin in a significant number of WATs, our results further show that these immunostains alone do not allow absolute distinction of WATs from sex cord-stromal tumors and adenomatoid tumors, respectively, with which they may be confused.
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PMID:Wolffian adnexal tumor, so-called female adnexal tumor of probable Wolffian origin (FATWO): immunohistochemical evidence in support of a Wolffian origin. 1041 6

Tumor progression after curative resection of colorectal cancer is caused by tumor cell dissemination, currently undetected by standard clinical staging techniques. The detection of disseminated tumor cells could help to identify a patient subgroup at risk for disease relapse who could benefit from adjuvant therapy. In addition, the significance of lymphogenic compared with hematogenic colorectal cancer cell dissemination is unknown. However, this knowledge would strongly influence the development of future therapeutic regimes. The purpose of this study was to determine the extent of colorectal cancer cell dissemination in lymph nodes compared with blood and bone marrow. Using a CK 20-reverse transcription (RT)-PCR assay, we examined 279 lymph nodes, blood, and bone marrow samples from 20 patients with colorectal cancer. Of 16 patients (11 patients stage I, 5 patients stage II) with histopathologically tumor-free lymph nodes: 14 patients (10 patients stage I, 4 patients stage II) were found to have tumor cells in paracolonic lymph nodes; 12 patients (8 patients stage I, 4 patients stage II) were found to have tumor cells in the lymph nodes along the mesentery vessels; and, remarkably, 6 patients (4 patients stage I, 2 patients stage II) were found to have tumor cells in the apical lymph nodes. In contrast, tumor cells were detected in only two blood and three bone marrow samples of these patients. Thus, lymphogenic tumor cell dissemination is a very common and early event in colorectal cancer, preceding hematogenic tumor cell dissemination. In addition, our data strongly suggest that the detection of tumor cells in the apical lymph node by CK 20-RT-PCR has prognostic relevance. Our results underline the therapeutic importance of meticulous lymph node dissection and demonstrate that the detection of lymphogenic or hematogenic tumor cell dissemination by CK 20-RT-PCR will significantly improve current tumor staging protocols.
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PMID:Detection of disseminated colorectal cancer cells in lymph nodes, blood and bone marrow. 1043 88

The suitability of CK20 mRNA expression as a marker for the detection of minimum residual disease in patients with cancer of epithelial origin was evaluated. A sensitive nested RT-PCR assay with multiple replicates was optimised to detect a minimum number of circulating tumor cells expressing cytokeratin 20 (CK20) mRNA. Using this optimal procedure, we examined CK20 mRNA expression in ten epithelial and seven leukemic cell lines, in eight bladder tumors, in peripheral blood samples from 18 tumor patients and from 29 healthy controls and in 8 bone marrow samples from healthy donors. CK20 mRNA was found in 13 of 18 (72%) blood samples from patients with cancer of epithelial origin and in all the epithelial tumor cells tested. However, CK20 mRNA was also detected in 21 of 29 (72%) bloods, in 8 of 8 bone marrow samples from healthy donors and in 4 of 7 leukemic cell lines. These results highlight a requirement for either determination of threshold levels of CK20 normal expression or the development of quantitative techniques to distinguish between a tumor-specific CK20 gene expression and a low level background transcription of this marker. These results would also advise caution in using CK20 as a tumor specific marker in clinical investigations.
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PMID:CK20 gene expression: technical limits for the detection of circulating tumor cells. 1047 Jan 50

More than half of all patients with invasive urothelial cancer subsequently develop metastatic disease even after radical resection of the primary cancer. In these patients, neoplastic cells may be disseminated prior to or during the operation. A nested reverse transcriptase-polymerase chain reaction (nested RT-PCR) assay which amplifies cytokeratin (CK) 20 transcripts was used to detect cancer cells in the peripheral blood of urothelial patients. This assay was able to detect 10 bladder cancer cell line cells in a sample of ten million peripheral-blood mononuclear (PBMN) cells. CK 20-specific signals were detected in 9 (22.5%) of 40 PBMN cell samples prepared from 40 urothelial cancer patients in relation to the tumor stage, including 0/13 patients with a superficial tumor, 4/21 (19%) with a regionally invasive tumor and 5/6 (83%) with a metastatic tumor (P = 0.0002 in chi 2 test). No signals were detected in any of 25 healthy donor PBMN cell samples. The present results indicate that the CK 20 RT-PCR assay is applicable for detection of urothelial cancer cells in the peripheral blood. The assay also confirms that hematogenic dissemination occurs in invasive urothelial cancers but rarely in superficial ones.
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PMID:Detection of disseminated urothelial cancer cells in peripheral venous blood by a cytokeratin 20-specific nested reverse transcriptase-polymerase chain reaction. 1047 Feb 88


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