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Donald A Sens - One of the best experts on this subject based on the ideXlab platform.
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Comparison of expression patterns of Keratin 6, 7, 16, 17, and 19 within multiple independent isolates of As(+3)- and Cd (+2)-induced bladder cancer : Keratin 6, 7, 16, 17, and 19 in bladder cancer.
Cell Biology and Toxicology, 2011Co-Authors: Seema Somji, Xu Dong Zhou, Aaron Mehus, Mary Ann Sens, Scott H Garrett, Jane R Dunlevy, Yun Zheng, Jennifer L. Larson, Donald A SensAbstract:This laboratory has generated a series of seven cadmium (Cd+2)- and six arsenite (As+3)-transformed urothelial cancer cell lines by exposure of parental UROtsa cells to each agent under similar conditions of exposure. In this study, the seven Cd+2-transformed cell lines were characterized for the expression of Keratin 6, 16, and 17 while the six As+3 cell lines were assessed for the expression of Keratin 7 and 19. The results showed that the series of Cd+2-transformed cell lines and their respective transplants all had expression of Keratin 6, 16, and 17 mRNA and protein. The expression of Keratin 6, 16, and 17 was also correlated with areas of the urothelial tumor cells that had undergone squamous differentiation. The results also showed that four of the six As+3-transformed cell lines had expression of Keratin 7 and 19 mRNA and protein and produced subcutaneous tumors with intense focal staining for Keratin 7 and 19. The other two As+3-transformed cell lines had very low expression of Keratin 7 mRNA and protein and produced subcutaneous tumors having no immunoreactivity for Keratin 7; although Keratin 19 expression was still present. The peritoneal tumors produced by one of these two cell lines regained expression of Keratin 7 protein. The present results, coupled with previous studies, indicate that malignant transformation of UROtsa cells by Cd+2 or As+3 produce similar patterns of Keratin 6, 7, 16, 17, and 19 in the resulting series of cell lines and their respective tumors.
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Comparison of expression patterns of Keratin 6, 7, 16, 17, and 19 within multiple independent isolates of As^+3- and Cd^+2-induced bladder cancer
Cell Biology and Toxicology, 2011Co-Authors: Seema Somji, Xu Dong Zhou, Aaron Mehus, Mary Ann Sens, Scott H Garrett, Jane R Dunlevy, Yun Zheng, Jennifer L. Larson, Donald A SensAbstract:This laboratory has generated a series of seven cadmium (Cd^+2)- and six arsenite (As^+3)-transformed urothelial cancer cell lines by exposure of parental UROtsa cells to each agent under similar conditions of exposure. In this study, the seven Cd^+2-transformed cell lines were characterized for the expression of Keratin 6, 16, and 17 while the six As^+3 cell lines were assessed for the expression of Keratin 7 and 19. The results showed that the series of Cd^+2-transformed cell lines and their respective transplants all had expression of Keratin 6, 16, and 17 mRNA and protein. The expression of Keratin 6, 16, and 17 was also correlated with areas of the urothelial tumor cells that had undergone squamous differentiation. The results also showed that four of the six As^+3-transformed cell lines had expression of Keratin 7 and 19 mRNA and protein and produced subcutaneous tumors with intense focal staining for Keratin 7 and 19. The other two As^+3-transformed cell lines had very low expression of Keratin 7 mRNA and protein and produced subcutaneous tumors having no immunoreactivity for Keratin 7; although Keratin 19 expression was still present. The peritoneal tumors produced by one of these two cell lines regained expression of Keratin 7 protein. The present results, coupled with previous studies, indicate that malignant transformation of UROtsa cells by Cd^+2 or As^+3 produce similar patterns of Keratin 6, 7, 16, 17, and 19 in the resulting series of cell lines and their respective tumors.
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variation of Keratin 7 expression and other phenotypic characteristics of independent isolates of cadmium transformed human urothelial cells urotsa
Chemical Research in Toxicology, 2010Co-Authors: Seema Somji, Xu Dong Zhou, Aaron Mehus, Mary Ann Sens, Scott H Garrett, Krista L Lutz, Jane R Dunlevy, Yun Zheng, Donald A SensAbstract:This laboratory has shown that a human urothelial cell line (UROtsa) transformed by cadmium (Cd 2+ ) produced subcutaneous tumor heterotransplants that resemble human transitional cell carcinoma (TCC). In the present study, additional Cd 2+ transformed cell lines were isolated to determine if independent exposures of the cell line to Cd 2+ would result in malignantly transformed cell lines possessing similar phenotypic properties. Seven independent isolates were isolated and assessed for their doubling times, morphology, ability to heterotransplant subcutaneously and in the peritoneal cavity of nude mice, and for the expression of Keratin 7. The 7 cell lines all displayed an epithelial morphology with no evidence of squamous differentiation. Doubling times were variable among the isolates, being significantly reduced or similar to those of the parental cells. All 7 isolates were able to form subcutaneous tumor heterotransplants with a TCC morphology, and all heterotransplants displayed areas of squamous differentiation of the transitional cells. The degree of squamous differentiation varied among the isolates. In contrast to subcutaneous tumor formation, only 1 isolate of the Cd 2+ transformed cells (UTCd#1) was able to effectively colonize multiple sites within the peritoneal cavity. An analysis of Keratin 7 expression showed no correlation with squamous differentiation for the subcutaneous heterotransplants generated from the 7 cell lines. Keratin 7 was expressed in 6 of the 7 cell lines and their subcutaneous tumor heterotransplants. Keratin 7 was not expressed in the cell line that was able to form tumors within the peritoneal cavity. These results show that individual isolates of Cd 2+ transformed cells have both similarities and differences in their phenotype.
L G Poels - One of the best experts on this subject based on the ideXlab platform.
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the applicability of a Keratin 7 monoclonal antibody in routinely papanicolaou stained cytologic specimens for the differential diagnosis of carcinomas
American Journal of Clinical Pathology, 1994Co-Authors: Janny H Baars, Frank Smedts, C C Van Niekerk, L G Poels, Jacqueline L M De Ruijter, Cornelis A Seldenrijk, Frans C S RamaekersAbstract:The monoclonal antibody OV-TL 12/30, witch detects Keratin 7, was tested for its usefulness in cytologic diagnosis by reincubating previously Papanicolaou-stained slides. For this purpose malignant effusions of 73 patients with histologically confirmed cancers of the colon, ovary, mesothelium, breast, lung, esophagus, pancreas, urinary bladder, stomach, kidney, and prostate were used. All malignant cells from ovarian adenocarcinomas were positive, whereas malignant cells from colonic adenocarcinomas and malignant mesotheliomas were negative. Adenocarcinomas of gastric, renal pancreatic, esophageal, and mammary origin demonstrated variable staining. Transitional cell carcinomas were positive, whereas squamous and small cell lung carcinomas were negative
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ov tl 12 30 Keratin 7 antibody is a marker of glandular differentiation in lung cancer
Histopathology, 1993Co-Authors: F Van De Molengraft, C C Van Niekerk, L G PoelsAbstract:The immunoreactivity of OV-TL 12/30, a monoclonal antibody to Keratin 7 was investigated on paraffin-embedded human lung cancer tissues of 61 patients. A modified AEC-immunoperoxidase method with pepsin pre-digestion was used. In normal lung tissue Keratin 7 was found in bronchial and bronchiolar epithelium, pneumocytes and compound glands. Squamous metaplasia of the bronchial tree was negative. All 24 squamous cell carcinomas were negative irrespective of grade of differentiation. All differentiation grades of 20 adenocarcinomas including bronchioalveolar carcinomas were positive. Since six large cell anaplastic carcinomas did not react with Keratin 7 antibody these tumours are considered to be of squamous cell rather than adenocarcinomatous origin. Small cell anaplastic carcinomas were negative in 10 of 11 cases. Our study demonstrates that this Keratin 7 antibody is useful in differentiating between squamous cell carcinoma and adenocarcinoma of the lung and it may be particularly useful in making the correct diagnosis in small lung biopsy specimens.
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immunohistochemical demonstration of Keratin 7 in routinely fixed paraffin embedded human tissues
The Journal of Pathology, 1991Co-Authors: Catharina C Van Niekerk, Frans C S Ramaekers, Fred Van De Molengraft, L G PoelsAbstract:The immunoreactivity of OV-TL 12/30, a monoclonal anti-Keratin 7 antibody (Mab), was investigated on frozen as well as paraffin-embedded human tissues. Its reactivity patterns were compared with another well-characterized monoclonal antibody to Keratin 7 (RCK 105), and with broadly cross-reacting monclonal (OV-TL 12/5) as well as polyclonal (pKer) Keratin antisera. In frozen sections of normal and malignant human tissues both Keratin 7 Mabs gave similar staining patterns. The immunoreactivity for OV-TL 12/30 and the polyclonal antibody (pKer) in tissue sections fixed in 4 per cent formalin or Bouin solution, was completely restored when pretreated with 0·1 per cent pronase, 0·1 per cent trypsin in phosphate-buffered saline (PBS) or with 0·5 per cent pepsin in 0·01 N HCl. Except for loss of immunoreactivity on human normal stomach surface epithelium and glandular mucous cells, Mab OV-TL 12/30 reacted strongly positive with essentially all those formalin- or Bouin-fixed paraffin-embedded tissues that had been shown to stain in non-fixed, frozen sections. In addition to the good correlation in normal human tissues, a complete correlation between the reactivity on frozen and paraffin-embedded human carcinomas (n = 86) was found as well. While both RCK 105 (anti-Keratin 7) and OV-TL 12/5 (anti-Keratin 5, 7, 14, 19) did not stain on paraffin-embedded sections, the polyclonal control antiserum (pKer) lost immunoreactivity in some cell types (e.g. mucous cells in compound glands, hepatocytes, pancreatic acinar cells, and proximal and distal convoluted tubules of the kidney). Our study shows that the Keratin 7 Mab OV-TL 12/30 is an excellent marker for tumour histopathology since it is reactive in paraffin-embedded formalin-fixed human tissues.
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use of monoclonal antibodies to Keratin 7 in the differential diagnosis of adenocarcinomas
American Journal of Pathology, 1990Co-Authors: F C S Ramaekers, G Schaart, C C Van Niekerk, L G Poels, E Schaafsma, A Huijsmans, H Robben, P VooijsAbstract:Monoclonal antibodies (MAbs) to specific Keratin subtypes were prepared and characterized by immunoblotting and immunohistochemical assays on human cell cultures and normal and malignant human tissues. Chain-specific MAbs to Keratin 7 (RCK 105, OV-TL 12/30) and Keratin 18 (RGE 53, RCK 106, CK18-2), as well as broadly cross-reacting Keratin MAbs (RCK 102, OV-TL 12/5) could be shown to react with different types of human epithelial tissues and were therefore tested for their usefulness in the differential diagnosis of carcinomas. The two broad-spectrum antibodies stained virtually all of the more than 350 carcinomas tested, especially when combined, and distinguished them from most nonepithelial tumors. The Keratin 18 MAbs distinguished adenocarcinomas (which are Keratin 18 positive) from most squamous cell carcinomas (which are generally Keratin 18 negative). The MAbs to Keratin 7 could be shown to recognize specific subtypes of adenocarcinoma and could, for example, distinguish between ovarian carcinomas (Keratin 7 positive) and carcinomas of the gastrointestinal tract (Keratin 7 negative), or between transitional cell carcinomas (Keratin 7 positive) and prostate cancer (Keratin 7 negative). In general, malignancies showed the expected Keratin reactivity pattern as concluded from the Keratin pattern of its cell of origin or its type of differentiation. The use of an extended series of malignancies did, however, also illustrate that exceptions to this rule exist. For example, certain antibodies to Keratin 18 stained tumor areas in squamous cell carcinomas of the lung. Also a certain percentage of tumors, which generally showed no Keratin 7 expression, were positive with RCK 105 or OV-TL 12/30. On the other hand, a certain percentage of tumors, which were generally positive for Keratin 7, did not show a staining reaction with these MAbs. Furthermore subtle differences between reactivity patterns of different MAbs recognizing the same Keratin protein were observed, both in the normal and malignant human tissues, indicating that specific Keratin epitopes may be masked in certain tissues and that unmasking of such epitopes can occur with malignant progression. This phenomenon may be of some use in a further subtyping of carcinomas, especially those of the gastrointestinal tract. Despite these exceptional staining patterns, the Keratin MAbs described above have proved to be useful tools in the characterization of epithelial tumors in routine histopathology and cytopathology, in which they add to a more refined diagnosis of (adeno)carcinomas.
Seema Somji - One of the best experts on this subject based on the ideXlab platform.
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Comparison of expression patterns of Keratin 6, 7, 16, 17, and 19 within multiple independent isolates of As(+3)- and Cd (+2)-induced bladder cancer : Keratin 6, 7, 16, 17, and 19 in bladder cancer.
Cell Biology and Toxicology, 2011Co-Authors: Seema Somji, Xu Dong Zhou, Aaron Mehus, Mary Ann Sens, Scott H Garrett, Jane R Dunlevy, Yun Zheng, Jennifer L. Larson, Donald A SensAbstract:This laboratory has generated a series of seven cadmium (Cd+2)- and six arsenite (As+3)-transformed urothelial cancer cell lines by exposure of parental UROtsa cells to each agent under similar conditions of exposure. In this study, the seven Cd+2-transformed cell lines were characterized for the expression of Keratin 6, 16, and 17 while the six As+3 cell lines were assessed for the expression of Keratin 7 and 19. The results showed that the series of Cd+2-transformed cell lines and their respective transplants all had expression of Keratin 6, 16, and 17 mRNA and protein. The expression of Keratin 6, 16, and 17 was also correlated with areas of the urothelial tumor cells that had undergone squamous differentiation. The results also showed that four of the six As+3-transformed cell lines had expression of Keratin 7 and 19 mRNA and protein and produced subcutaneous tumors with intense focal staining for Keratin 7 and 19. The other two As+3-transformed cell lines had very low expression of Keratin 7 mRNA and protein and produced subcutaneous tumors having no immunoreactivity for Keratin 7; although Keratin 19 expression was still present. The peritoneal tumors produced by one of these two cell lines regained expression of Keratin 7 protein. The present results, coupled with previous studies, indicate that malignant transformation of UROtsa cells by Cd+2 or As+3 produce similar patterns of Keratin 6, 7, 16, 17, and 19 in the resulting series of cell lines and their respective tumors.
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Comparison of expression patterns of Keratin 6, 7, 16, 17, and 19 within multiple independent isolates of As^+3- and Cd^+2-induced bladder cancer
Cell Biology and Toxicology, 2011Co-Authors: Seema Somji, Xu Dong Zhou, Aaron Mehus, Mary Ann Sens, Scott H Garrett, Jane R Dunlevy, Yun Zheng, Jennifer L. Larson, Donald A SensAbstract:This laboratory has generated a series of seven cadmium (Cd^+2)- and six arsenite (As^+3)-transformed urothelial cancer cell lines by exposure of parental UROtsa cells to each agent under similar conditions of exposure. In this study, the seven Cd^+2-transformed cell lines were characterized for the expression of Keratin 6, 16, and 17 while the six As^+3 cell lines were assessed for the expression of Keratin 7 and 19. The results showed that the series of Cd^+2-transformed cell lines and their respective transplants all had expression of Keratin 6, 16, and 17 mRNA and protein. The expression of Keratin 6, 16, and 17 was also correlated with areas of the urothelial tumor cells that had undergone squamous differentiation. The results also showed that four of the six As^+3-transformed cell lines had expression of Keratin 7 and 19 mRNA and protein and produced subcutaneous tumors with intense focal staining for Keratin 7 and 19. The other two As^+3-transformed cell lines had very low expression of Keratin 7 mRNA and protein and produced subcutaneous tumors having no immunoreactivity for Keratin 7; although Keratin 19 expression was still present. The peritoneal tumors produced by one of these two cell lines regained expression of Keratin 7 protein. The present results, coupled with previous studies, indicate that malignant transformation of UROtsa cells by Cd^+2 or As^+3 produce similar patterns of Keratin 6, 7, 16, 17, and 19 in the resulting series of cell lines and their respective tumors.
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variation of Keratin 7 expression and other phenotypic characteristics of independent isolates of cadmium transformed human urothelial cells urotsa
Chemical Research in Toxicology, 2010Co-Authors: Seema Somji, Xu Dong Zhou, Aaron Mehus, Mary Ann Sens, Scott H Garrett, Krista L Lutz, Jane R Dunlevy, Yun Zheng, Donald A SensAbstract:This laboratory has shown that a human urothelial cell line (UROtsa) transformed by cadmium (Cd 2+ ) produced subcutaneous tumor heterotransplants that resemble human transitional cell carcinoma (TCC). In the present study, additional Cd 2+ transformed cell lines were isolated to determine if independent exposures of the cell line to Cd 2+ would result in malignantly transformed cell lines possessing similar phenotypic properties. Seven independent isolates were isolated and assessed for their doubling times, morphology, ability to heterotransplant subcutaneously and in the peritoneal cavity of nude mice, and for the expression of Keratin 7. The 7 cell lines all displayed an epithelial morphology with no evidence of squamous differentiation. Doubling times were variable among the isolates, being significantly reduced or similar to those of the parental cells. All 7 isolates were able to form subcutaneous tumor heterotransplants with a TCC morphology, and all heterotransplants displayed areas of squamous differentiation of the transitional cells. The degree of squamous differentiation varied among the isolates. In contrast to subcutaneous tumor formation, only 1 isolate of the Cd 2+ transformed cells (UTCd#1) was able to effectively colonize multiple sites within the peritoneal cavity. An analysis of Keratin 7 expression showed no correlation with squamous differentiation for the subcutaneous heterotransplants generated from the 7 cell lines. Keratin 7 was expressed in 6 of the 7 cell lines and their subcutaneous tumor heterotransplants. Keratin 7 was not expressed in the cell line that was able to form tumors within the peritoneal cavity. These results show that individual isolates of Cd 2+ transformed cells have both similarities and differences in their phenotype.
Nelson G. Ordóñez - One of the best experts on this subject based on the ideXlab platform.
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Mesothelioma with signet-ring cell features: report of 23 cases
Modern Pathology, 2012Co-Authors: Nelson G. OrdóñezAbstract:Signet-ring cell mesothelioma is uncommon and only two case reports have been published on this mesothelioma variant, both of which were initially misdiagnosed as signet-ring cell carcinoma. Herein are reported 23 signet-ring cell mesotheliomas that were investigated by immunohistochemistry, 12 of which were also studied by electron microscopy. Twenty-one of the cases originated in the pleura and two in the peritoneum. For comparison purposes and in order to determine the value of these techniques in the differential diagnosis of these tumors, seven cases of signet-ring cell lung adenocarcinoma were also studied. All signet-ring cell mesotheliomas were positive for calretinin, Keratin 5/6, Keratin 7, and mesothelin, 93% for podoplanin, and 91% for WT1; whereas, none reacted for MOC-31, CEA, TAG-72, CD15, TTF-1, napsin A, or CDX2. Among signet-ring cell lung adenocarcinomas, 100% were positive for Keratin 7, CEA, and napsin A, 86% each for TTF-1 and TAG-72, 71% for CD15, and 14% for mesothelin, while all were negative for calretinin, Keratin 5/6, WT1, podoplanin, and CDX2. After analyzing the results, it is concluded that the panels of markers used in the differential diagnosis of this mesothelioma variant should include those markers that are usually expressed in mesotheliomas (eg, calretinin, Keratin 5/6, WT1, and podoplanin), broad-spectrum carcinoma markers that are frequently expressed in adenocarcinomas regardless of their site of origin (eg, MOC-31 and CEA), and organ-associated markers (eg, TTF-1 and napsin A for lung), which allow the site of origin of a metastatic adenocarcinoma to be established. Electron microscopy can be very useful as it permits the identification of characteristic ultrastructural mesothelioma and adenocarcinoma markers, and it also allows a better understanding of the morphologic features seen on routine light microscopy. Pathologists should be aware of this mesothelioma subtype as it can potentially be confused with other tumors that exhibit signet-ring features.
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Mesotheliomas with small cell features: report of eight cases
Modern Pathology, 2012Co-Authors: Nelson G. OrdóñezAbstract:Mesotheliomas with small cell morphology are rare and only one study of such cases has been published. As a result of their rare occurrence, some investigators have cast doubt on the existence of such a histologic variant of mesothelioma. This investigator reports a series of eight cases of epithelioid mesothelioma with small cell features, all of which originated in the pleura. Seven of the patients were men and one was a woman. Four patients had a history of asbestos exposure. Histologically, four of the mesotheliomas were epithelioid and four biphasic. The proportion of small cells seen in these cases constituted 80 to 100% of the tumor included in the biopsy material and 15 to 20% of the tumor present in the pneumonectomy specimens. Immunoreactivity for calretinin, Keratin 5/6, Keratin 7, pan-Keratin, WT1, podoplanin, and mesothelin was seen in all cases tested for these markers. All of the cases were negative for MOC-31, Ber-EP4, CEA, CD15, TAG-72, TTF-1, chromogranin A, synaptophysin, CD99, and desmin. The mean survival of the six patients for whom this information was available was 8.2 months. It is important for pathologists to be aware that mesotheliomas can present small cell features and, because of this, they can be confused with other malignancies that can exhibit similar morphology. The value of immunohistochemistry in the differential diagnosis of these tumors is discussed.
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Mesothelioma with rhabdoid features: an ultrastructural and immunohistochemical study of 10 cases
Modern Pathology, 2006Co-Authors: Nelson G. OrdóñezAbstract:Mesotheliomas with rhabdoid morphology are rare and only two individual case reports have been documented in the literature. This author reports a series of 10 cases of mesotheliomas with rhabdoid features, nine of which originated in the pleura and one in the peritoneum. Eight of the patients were men and two were women. Six patients had a history of asbestos exposure. Histologically, seven of the mesotheliomas were epithelioid, two sarcomatoid, and one biphasic. The proportion of the rhabdoid cells seen in these cases constituted 15–75% of the individual tumors. Cytoplasmic staining in the rhabdoid cells was seen for pan-Keratin and vimentin in all 10 cases, for Keratin 7 in eight of eight, for calretinin in nine of 10, and for Keratin 5/6 in seven of nine. Nuclear positivity for WT1 was observed in the rhabdoid cells of four of seven cases and membranous reactivity for mesothelin in four of six, and for podoplanin in two of six. Only one case showed desmin positivity in sparse cells in the nonrhabdoid component of the tumor. All of the cases were negative for CEA, MOC-31, TAG-72, CD15, CD34, bcl2, muscle-specific actin, and TTF-1. Ultrastructural studies revealed paranuclear collections of intermediate filaments, but no evidence of rhabdomyoblastic differentiation was seen. The mean survival of five of the six patients for whom this information was available was 3.8 months. The remaining patient had a survival time of 1 year. It is important for pathologists to be aware that mesotheliomas can present rhabdoid features, not only because they can be confused with other malignancies that can exhibit a similar morphology, but also because of their apparently unusually aggressive behavior. The value of immunohistochemistry and electron microscopy in the differential diagnosis of these tumors is discussed.
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The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study
Modern Pathology, 2006Co-Authors: Nelson G. OrdóñezAbstract:As both mesotheliomas and squamous carcinomas can present a wide variety of morphological patterns, they can on occasion be confused. Recently, some groups of investigators have called attention to the difficulties that sometimes exist in distinguishing between these malignancies and the need to define a panel of markers that can assist in reaching the correct diagnosis. The aim of the present study is to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and squamous carcinoma of the lung. A total of 30 epithelioid pleural mesotheliomas exhibiting a solid or predominantly solid pattern, and 30 nonKeratinizing squamous carcinomas of the lung were investigated for the expression of the following markers: podoplanin, calretinin, mesothelin, WT1, Keratin 5/6, Keratin 7, p63, carcinoembryonic antigen (CEA), MOC-31, Ber-EP4, B72.3, BG-8 (Lewisy), leu-M1 (CD15), and thyroid transcription factor-1 (TTF-1). All 30 (100%) of the mesotheliomas reacted for calretinin, mesothelin and Keratin 7, 93% each for podoplanin, WT1 and Keratin 5/6, 13% for Ber-EP4, 7% each for p63, MOC-31 and BG-8, and 0% for B72.3, CEA, leu-M1 and TTF-1. All 30 (100%) of the squamous carcinomas were positive for p63 and Keratin 5/6, 97% for MOC-31, 87% for Ber-EP4, 80% for BG-8, 77% for CEA, 57% for Keratin 7, 40% for calretinin and B72.3, 30% for leu-M1, 27% for mesothelin, 15% for podoplanin, and 0% for WT 1 and TTF-1. After analyzing the results, it is concluded that from a practical point-of-view, a combination of two positive mesothelioma markers (WT1 and calretinin or mesothelin) with two negative mesothelioma markers (p63 and MOC-31) would allow the differential diagnosis to be established between epithelioid mesotheliomas and squamous carcinomas of the lung in nearly all instances.
Mary Ann Sens - One of the best experts on this subject based on the ideXlab platform.
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Comparison of expression patterns of Keratin 6, 7, 16, 17, and 19 within multiple independent isolates of As(+3)- and Cd (+2)-induced bladder cancer : Keratin 6, 7, 16, 17, and 19 in bladder cancer.
Cell Biology and Toxicology, 2011Co-Authors: Seema Somji, Xu Dong Zhou, Aaron Mehus, Mary Ann Sens, Scott H Garrett, Jane R Dunlevy, Yun Zheng, Jennifer L. Larson, Donald A SensAbstract:This laboratory has generated a series of seven cadmium (Cd+2)- and six arsenite (As+3)-transformed urothelial cancer cell lines by exposure of parental UROtsa cells to each agent under similar conditions of exposure. In this study, the seven Cd+2-transformed cell lines were characterized for the expression of Keratin 6, 16, and 17 while the six As+3 cell lines were assessed for the expression of Keratin 7 and 19. The results showed that the series of Cd+2-transformed cell lines and their respective transplants all had expression of Keratin 6, 16, and 17 mRNA and protein. The expression of Keratin 6, 16, and 17 was also correlated with areas of the urothelial tumor cells that had undergone squamous differentiation. The results also showed that four of the six As+3-transformed cell lines had expression of Keratin 7 and 19 mRNA and protein and produced subcutaneous tumors with intense focal staining for Keratin 7 and 19. The other two As+3-transformed cell lines had very low expression of Keratin 7 mRNA and protein and produced subcutaneous tumors having no immunoreactivity for Keratin 7; although Keratin 19 expression was still present. The peritoneal tumors produced by one of these two cell lines regained expression of Keratin 7 protein. The present results, coupled with previous studies, indicate that malignant transformation of UROtsa cells by Cd+2 or As+3 produce similar patterns of Keratin 6, 7, 16, 17, and 19 in the resulting series of cell lines and their respective tumors.
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Comparison of expression patterns of Keratin 6, 7, 16, 17, and 19 within multiple independent isolates of As^+3- and Cd^+2-induced bladder cancer
Cell Biology and Toxicology, 2011Co-Authors: Seema Somji, Xu Dong Zhou, Aaron Mehus, Mary Ann Sens, Scott H Garrett, Jane R Dunlevy, Yun Zheng, Jennifer L. Larson, Donald A SensAbstract:This laboratory has generated a series of seven cadmium (Cd^+2)- and six arsenite (As^+3)-transformed urothelial cancer cell lines by exposure of parental UROtsa cells to each agent under similar conditions of exposure. In this study, the seven Cd^+2-transformed cell lines were characterized for the expression of Keratin 6, 16, and 17 while the six As^+3 cell lines were assessed for the expression of Keratin 7 and 19. The results showed that the series of Cd^+2-transformed cell lines and their respective transplants all had expression of Keratin 6, 16, and 17 mRNA and protein. The expression of Keratin 6, 16, and 17 was also correlated with areas of the urothelial tumor cells that had undergone squamous differentiation. The results also showed that four of the six As^+3-transformed cell lines had expression of Keratin 7 and 19 mRNA and protein and produced subcutaneous tumors with intense focal staining for Keratin 7 and 19. The other two As^+3-transformed cell lines had very low expression of Keratin 7 mRNA and protein and produced subcutaneous tumors having no immunoreactivity for Keratin 7; although Keratin 19 expression was still present. The peritoneal tumors produced by one of these two cell lines regained expression of Keratin 7 protein. The present results, coupled with previous studies, indicate that malignant transformation of UROtsa cells by Cd^+2 or As^+3 produce similar patterns of Keratin 6, 7, 16, 17, and 19 in the resulting series of cell lines and their respective tumors.
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variation of Keratin 7 expression and other phenotypic characteristics of independent isolates of cadmium transformed human urothelial cells urotsa
Chemical Research in Toxicology, 2010Co-Authors: Seema Somji, Xu Dong Zhou, Aaron Mehus, Mary Ann Sens, Scott H Garrett, Krista L Lutz, Jane R Dunlevy, Yun Zheng, Donald A SensAbstract:This laboratory has shown that a human urothelial cell line (UROtsa) transformed by cadmium (Cd 2+ ) produced subcutaneous tumor heterotransplants that resemble human transitional cell carcinoma (TCC). In the present study, additional Cd 2+ transformed cell lines were isolated to determine if independent exposures of the cell line to Cd 2+ would result in malignantly transformed cell lines possessing similar phenotypic properties. Seven independent isolates were isolated and assessed for their doubling times, morphology, ability to heterotransplant subcutaneously and in the peritoneal cavity of nude mice, and for the expression of Keratin 7. The 7 cell lines all displayed an epithelial morphology with no evidence of squamous differentiation. Doubling times were variable among the isolates, being significantly reduced or similar to those of the parental cells. All 7 isolates were able to form subcutaneous tumor heterotransplants with a TCC morphology, and all heterotransplants displayed areas of squamous differentiation of the transitional cells. The degree of squamous differentiation varied among the isolates. In contrast to subcutaneous tumor formation, only 1 isolate of the Cd 2+ transformed cells (UTCd#1) was able to effectively colonize multiple sites within the peritoneal cavity. An analysis of Keratin 7 expression showed no correlation with squamous differentiation for the subcutaneous heterotransplants generated from the 7 cell lines. Keratin 7 was expressed in 6 of the 7 cell lines and their subcutaneous tumor heterotransplants. Keratin 7 was not expressed in the cell line that was able to form tumors within the peritoneal cavity. These results show that individual isolates of Cd 2+ transformed cells have both similarities and differences in their phenotype.
