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Normand Marceau - One of the best experts on this subject based on the ideXlab platform.
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down regulation of Cytokeratin 14 gene expression by the polyoma virus middle t antigen is dependent on c src association but independent of full transformation in rat liver nonparenchymal epithelial cells
Cell Growth & Differentiation, 1996Co-Authors: Isabelle Royal, Leda Raptis, Brian Druker, Normand MarceauAbstract:Polyoma virus middle T antigen (mT) transforms the T51B cell line and induces the loss of the Cytokeratin 8 and 14 pair (CK8/CK14) present in these rat nonparenchymal liver epithelial cells (LECs), because of the selective down-regulation of CK14 gene expression. To identify the initial steps of the mT-induced signaling pathway(s) leading to this inhibition, T51B cells were transfected with vectors encoding the NG59, dl23, and 248M mT mutants, which are known to interact in a differential manner with c-Src, P13-kinase, and Shc. Immunofluorescence microscopy and Northern blot analysis showed a loss of Cytokeratins in dl23 or 248M but not in NG59 mT mutant-containing cells. An in vitro kinase assay demonstrated that only the dl23 and 248M mT mutants could associate with c-Src. This c-Src-mediated action of mT on CK14 gene expression was further confirmed by adding the v-src gene product in T51B cells. The assessment of the transforming capacity of the mT mutants demonstrated that the NG59 and dl23 mT mutants were nontransformant, whereas the 248M mT mutant expressed an appreciable transforming activity. These results show that the down-regulation of CK14 gene expression by mT in the LEC line T51B is dependent on the association with the c-Src tyrosine kinase, but interestingly, this c-Src-mediated action of mT can occur in the absence of transformation. Furthermore, when coupled with recent data on the plasticity of LECs, the present findings provide the first essential element in our definition of the signaling pathway(s) that link growth/differentiation events with CK gene regulation in typical simple epithelial cells.
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polyomavirus middle t selective action on Cytokeratin 14 gene expression in liver nonparenchymal epithelial cells
Experimental Cell Research, 1995Co-Authors: Isabelle Royal, Andree Grenier, Donald Mailhot, Normand MarceauAbstract:We reported recently that liver nonparenchymal epithelial cells (LECs) constitute a small population of cells scattered throughout biliary structures and the Glisson's capsule, containing the unusual Cytokeratin (CK) pair CK8/CK14 (Blouin et al., Differentiation, 1992, 52, 45). The transfection of polyomavirus middle T oncogene (MT) into the LEC line T51B leads to the loss of their CKs, due to a down-regulation of CK14 gene expression (Royal et al., Cell Growth Differ., 1992, 3, 589). In the present work, we examined CK gene expression at both mRNA and protein levels following polyomavirus small T oncogene (ST), MT, or large T oncogene (LT) transfection of T51B cells, MT transfection of rat hepatic cell lines containing different subsets of CKs, and MT transfection of rat keratinocytes. Immunofluorescence staining revealed that MT indeed induced an inhibition of CK14 gene expression and a loss of CK8/CK14 intermediate filaments (IFs) in liver cells, whereas ST and LT had no effect. Moreover, CK14 was the only CK gene whose expression was inhibited in MT-containing hepatic cells, in the sense that the expression of the CK7, CK8, CK18, and CK19 genes was not affected. Two-dimensional SDS-PAGE of the Triton-resistant cytoskeletal proteins and Northern blotting of the CK mRNA content confirmed these findings. The transfer of the MT oncogene into the keratinocytes did not result in the loss of CK5/CK14 IFs nor the inhibition of CK14 gene expression. These results show that the polyomavirus oncogene action on CK gene expression is restricted to an MT effect on CK14 in rat LECs.
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Cytokeratin 14 expression in rat liver cells in culture and localization in vivo
Differentiation, 1992Co-Authors: Richard Blouin, Mariejose Blouin, Isabelle Royal, Andree Grenier, Dennis R Roop, Anne Loranger, Normand MarceauAbstract:Abstract Rat liver epithelial cells (LECs) are non-parenchymal proliferating cells that readily emerge in primary culture and can be established as cell lines, but their in vivo cell(s) of origin is unclear. We reported recently some evidence indicating that the LEC line, T51B, contains two Cytokeratins (CKs) equivalent to human CK8 and CK14 respectively. T51B cells also contain vimentin assembled as a network of intermediate filaments distinct from that of the CKs. In the present study, we examined the expression of CK14 gene in various LEC preparations and a Triton-resistant rat skin cytoskeletal fraction, and then assessed its usefulness as an LEC specific marker in the liver. Northern and Western blot analyses with cDNAs and antibodies for CK8, CK14, CK18 and vimentin confirmed that rat hepatocytes express CK8 and CK18 genes only, whereas T51B cells express CK8, CK14 and vimentin genes in the absence of CK18. CK14 was also present in LECs derived as primary from embryonic-day 12 rat liver and secondary cultures from 4-day-old rat liver. Primary cultures of oval cells isolated from 3′-methyl-4-dimethylaminoazobenzene (3′-Me-DAB) treated rat liver (an enriched source of biliary epithelial cells) contained CK14 mRNAs which were slightly shorter than those in LECs. The analyses of CK5 (the usual partner of CK14) gene expression using specific cDNA and antibody clearly demonstrated its absence in LECs. In situ double immunolocalization analyses by laser scanning confocal microscopy showed that CK14 was not present in hepatocytes (HES + 6 cells) and was expressed in some biliary epithelial (BDS 7 + cells). CK14-positive cells were also found in the Glisson's capsule. However, CK14-positive cells of the portal region were vimentin negative, whereas those of the Glisson's capsule were vimentin positive. Our results suggest that CK14 gene expression is part of the differentiation program of two types of LECs and that this differential CK14 gene expression can be used as a new means to type LECs in culture and in vivo.
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down regulation of Cytokeratin 14 mrna in polyoma virus middle t transformed rat liver epithelial cells
Cell Growth & Differentiation, 1992Co-Authors: Isabelle Royal, Richard Blouin, Henriette Gourdeau, Normand MarceauAbstract:We have recently shown that rat liver nonparenchymal epithelial cells, such as T51B cells, selectively express Cytokeratin (CK) 14 as a partner of CK8 in their intermediate filaments, and we proposed CK14 as a unique cell lineage marker of the liver epithelial cell population (R. Blouin, M-J. Blouin, I. Royal, A. Grenier, A. Loranger, D. R. Roop, and N. Marceau, Differentiation, submitted for publication, 1992). In the present study, T51B-261A (spontaneously transformed) and T51B-261B (aflatoxin B1-treated) clones and clones derived from T51B cells transfected with SV40 large T (LT) and polyoma virus middle T (MT) were used to investigate CK gene expression in nontransformed and transformed liver epithelial cells. T51B-261A, T51B-261B, MT-T51B, and LT/MT-T51B clones all grew in calcium-deficient medium and formed colonies in soft agar, whereas LT-T51B clones did not grow at all in either one of these assays. T51B-261A and T51B-261B clones formed small, slow growing tumors when injected into newborn syngenic rats, whereas the MT-T51B and LT/MT-T51B clones produced rapidly forming, large tumors. There was no effect of cell transformation on CK expression, except in the clones expressing MT, where the CK intermediate filaments were completely lost. Analyses of [35S]methionine incorporation into the Triton-resistant cytoskeleton and of total proteins confirmed that CKs were absent. In contrast, vimentin intermediate filaments remained unaffected in all of the clones.(ABSTRACT TRUNCATED AT 250 WORDS)
Isabelle Royal - One of the best experts on this subject based on the ideXlab platform.
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down regulation of Cytokeratin 14 gene expression by the polyoma virus middle t antigen is dependent on c src association but independent of full transformation in rat liver nonparenchymal epithelial cells
Cell Growth & Differentiation, 1996Co-Authors: Isabelle Royal, Leda Raptis, Brian Druker, Normand MarceauAbstract:Polyoma virus middle T antigen (mT) transforms the T51B cell line and induces the loss of the Cytokeratin 8 and 14 pair (CK8/CK14) present in these rat nonparenchymal liver epithelial cells (LECs), because of the selective down-regulation of CK14 gene expression. To identify the initial steps of the mT-induced signaling pathway(s) leading to this inhibition, T51B cells were transfected with vectors encoding the NG59, dl23, and 248M mT mutants, which are known to interact in a differential manner with c-Src, P13-kinase, and Shc. Immunofluorescence microscopy and Northern blot analysis showed a loss of Cytokeratins in dl23 or 248M but not in NG59 mT mutant-containing cells. An in vitro kinase assay demonstrated that only the dl23 and 248M mT mutants could associate with c-Src. This c-Src-mediated action of mT on CK14 gene expression was further confirmed by adding the v-src gene product in T51B cells. The assessment of the transforming capacity of the mT mutants demonstrated that the NG59 and dl23 mT mutants were nontransformant, whereas the 248M mT mutant expressed an appreciable transforming activity. These results show that the down-regulation of CK14 gene expression by mT in the LEC line T51B is dependent on the association with the c-Src tyrosine kinase, but interestingly, this c-Src-mediated action of mT can occur in the absence of transformation. Furthermore, when coupled with recent data on the plasticity of LECs, the present findings provide the first essential element in our definition of the signaling pathway(s) that link growth/differentiation events with CK gene regulation in typical simple epithelial cells.
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polyomavirus middle t selective action on Cytokeratin 14 gene expression in liver nonparenchymal epithelial cells
Experimental Cell Research, 1995Co-Authors: Isabelle Royal, Andree Grenier, Donald Mailhot, Normand MarceauAbstract:We reported recently that liver nonparenchymal epithelial cells (LECs) constitute a small population of cells scattered throughout biliary structures and the Glisson's capsule, containing the unusual Cytokeratin (CK) pair CK8/CK14 (Blouin et al., Differentiation, 1992, 52, 45). The transfection of polyomavirus middle T oncogene (MT) into the LEC line T51B leads to the loss of their CKs, due to a down-regulation of CK14 gene expression (Royal et al., Cell Growth Differ., 1992, 3, 589). In the present work, we examined CK gene expression at both mRNA and protein levels following polyomavirus small T oncogene (ST), MT, or large T oncogene (LT) transfection of T51B cells, MT transfection of rat hepatic cell lines containing different subsets of CKs, and MT transfection of rat keratinocytes. Immunofluorescence staining revealed that MT indeed induced an inhibition of CK14 gene expression and a loss of CK8/CK14 intermediate filaments (IFs) in liver cells, whereas ST and LT had no effect. Moreover, CK14 was the only CK gene whose expression was inhibited in MT-containing hepatic cells, in the sense that the expression of the CK7, CK8, CK18, and CK19 genes was not affected. Two-dimensional SDS-PAGE of the Triton-resistant cytoskeletal proteins and Northern blotting of the CK mRNA content confirmed these findings. The transfer of the MT oncogene into the keratinocytes did not result in the loss of CK5/CK14 IFs nor the inhibition of CK14 gene expression. These results show that the polyomavirus oncogene action on CK gene expression is restricted to an MT effect on CK14 in rat LECs.
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Cytokeratin 14 expression in rat liver cells in culture and localization in vivo
Differentiation, 1992Co-Authors: Richard Blouin, Mariejose Blouin, Isabelle Royal, Andree Grenier, Dennis R Roop, Anne Loranger, Normand MarceauAbstract:Abstract Rat liver epithelial cells (LECs) are non-parenchymal proliferating cells that readily emerge in primary culture and can be established as cell lines, but their in vivo cell(s) of origin is unclear. We reported recently some evidence indicating that the LEC line, T51B, contains two Cytokeratins (CKs) equivalent to human CK8 and CK14 respectively. T51B cells also contain vimentin assembled as a network of intermediate filaments distinct from that of the CKs. In the present study, we examined the expression of CK14 gene in various LEC preparations and a Triton-resistant rat skin cytoskeletal fraction, and then assessed its usefulness as an LEC specific marker in the liver. Northern and Western blot analyses with cDNAs and antibodies for CK8, CK14, CK18 and vimentin confirmed that rat hepatocytes express CK8 and CK18 genes only, whereas T51B cells express CK8, CK14 and vimentin genes in the absence of CK18. CK14 was also present in LECs derived as primary from embryonic-day 12 rat liver and secondary cultures from 4-day-old rat liver. Primary cultures of oval cells isolated from 3′-methyl-4-dimethylaminoazobenzene (3′-Me-DAB) treated rat liver (an enriched source of biliary epithelial cells) contained CK14 mRNAs which were slightly shorter than those in LECs. The analyses of CK5 (the usual partner of CK14) gene expression using specific cDNA and antibody clearly demonstrated its absence in LECs. In situ double immunolocalization analyses by laser scanning confocal microscopy showed that CK14 was not present in hepatocytes (HES + 6 cells) and was expressed in some biliary epithelial (BDS 7 + cells). CK14-positive cells were also found in the Glisson's capsule. However, CK14-positive cells of the portal region were vimentin negative, whereas those of the Glisson's capsule were vimentin positive. Our results suggest that CK14 gene expression is part of the differentiation program of two types of LECs and that this differential CK14 gene expression can be used as a new means to type LECs in culture and in vivo.
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down regulation of Cytokeratin 14 mrna in polyoma virus middle t transformed rat liver epithelial cells
Cell Growth & Differentiation, 1992Co-Authors: Isabelle Royal, Richard Blouin, Henriette Gourdeau, Normand MarceauAbstract:We have recently shown that rat liver nonparenchymal epithelial cells, such as T51B cells, selectively express Cytokeratin (CK) 14 as a partner of CK8 in their intermediate filaments, and we proposed CK14 as a unique cell lineage marker of the liver epithelial cell population (R. Blouin, M-J. Blouin, I. Royal, A. Grenier, A. Loranger, D. R. Roop, and N. Marceau, Differentiation, submitted for publication, 1992). In the present study, T51B-261A (spontaneously transformed) and T51B-261B (aflatoxin B1-treated) clones and clones derived from T51B cells transfected with SV40 large T (LT) and polyoma virus middle T (MT) were used to investigate CK gene expression in nontransformed and transformed liver epithelial cells. T51B-261A, T51B-261B, MT-T51B, and LT/MT-T51B clones all grew in calcium-deficient medium and formed colonies in soft agar, whereas LT-T51B clones did not grow at all in either one of these assays. T51B-261A and T51B-261B clones formed small, slow growing tumors when injected into newborn syngenic rats, whereas the MT-T51B and LT/MT-T51B clones produced rapidly forming, large tumors. There was no effect of cell transformation on CK expression, except in the clones expressing MT, where the CK intermediate filaments were completely lost. Analyses of [35S]methionine incorporation into the Triton-resistant cytoskeleton and of total proteins confirmed that CKs were absent. In contrast, vimentin intermediate filaments remained unaffected in all of the clones.(ABSTRACT TRUNCATED AT 250 WORDS)
Lawrence Weiss - One of the best experts on this subject based on the ideXlab platform.
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Cytokeratin 14 immunoreactivity distinguishes oncocytic tumour from its renal mimics an immunohistochemical study of 63 cases
Histopathology, 2001Co-Authors: Peiguo G Chu, Lawrence WeissAbstract:Cytokeratin 14 immunoreactivity distinguishes oncocytic tumour from its renal mimics: an immunohistochemical study of 63 cases Aims: The Cytokeratin 14 (CK14) expression in oncocytomas or oncocytic tumours of various tissue origins has not been established. We have studied CK14 expression in 30 cases of oncocytic tumours of various tissue origins and 33 cases of renal cell carcinoma with overlapping features (mimics) by immunohistochemistry. Methods and results: Immunohistochemistry (ABC–HRP method) was performed for detection of CK14 in 30 cases of oncocytic tumour and 33 cases of renal mimics. To demonstrate CK14 specificity and sensitivity in oncocytic tumours, mES-13 (an anti-mitochondrial monoclonal antibody) immunohistochemistry was also performed in 20 of 30 cases on oncocytic tumour and all 33 cases of renal mimics. We found that all 30 cases of oncocytic tumour showed cytoplasmic CK14 positivity. All 20 cases of oncocytic tumour studied with mES-13 were positive. CK14 immunoreactivity was identified in only four cases of renal cell carcinoma (one conventional renal cell carcinoma with granular cytoplasm and three chromophobe renal cell carcinomas with eosinophilic cytoplasm). In contrast, all 33 cases of renal cell carcinoma were positive for mES-13 to varying degrees. Conclusion: The homogeneous, cytoplasmic, and granular CK14 immunoreactivity is sensitive and specific for oncocytic tumours, whereas CK14 immunoreactivity in renal mimics is light and sporadic with peripheral accentuation.
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Cytokeratin 14 expression in epithelial neoplasms a survey of 435 cases with emphasis on its value in differentiating squamous cell carcinomas from other epithelial tumours
Histopathology, 2001Co-Authors: Peiguo G Chu, Mark H Lyda, Lawrence WeissAbstract:Cytokeratin 14 expression in epithelial neoplasms: a survey of 435 cases with emphasis on its value in differentiating squamous cell carcinomas from other epithelial tumours Aims: The tissue distribution of Cytokeratin 14 (CK14) in epithelial neoplasms is not well defined. We have evaluated 435 cases of epithelial neoplasm of various origins with Cytokeratin 14 monoclonal antibody with special attention to possible use in differential diagnosis. Methods and results: Immunohistochemistry (ABC–HRP method) was performed for detection of CK14. We found that the expression of Cytokeratin 14 was generally restricted to: (i) the majority of cases of squamous cell carcinoma regardless of origin (67/74) and degree of differentiation; (ii) neoplasms with focal squamous differentiation, including endometrial, and ovarian adenocarcinoma, malignant mesothelioma and transitional cell carcinoma; (iii) thymoma (8/8); (iv) myoepithelial components of salivary gland pleomorphic adenoma (3/4); and (v) oncocytic neoplasms, including thyroid Hurthle cell adenoma (1/1) and salivary gland Warthin’s tumour (2/2). Conclusion: CK14 protein is a useful marker in differential diagnosis of squamous cell carcinomas.
Richard Blouin - One of the best experts on this subject based on the ideXlab platform.
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Cytokeratin 14 expression in rat liver cells in culture and localization in vivo
Differentiation, 1992Co-Authors: Richard Blouin, Mariejose Blouin, Isabelle Royal, Andree Grenier, Dennis R Roop, Anne Loranger, Normand MarceauAbstract:Abstract Rat liver epithelial cells (LECs) are non-parenchymal proliferating cells that readily emerge in primary culture and can be established as cell lines, but their in vivo cell(s) of origin is unclear. We reported recently some evidence indicating that the LEC line, T51B, contains two Cytokeratins (CKs) equivalent to human CK8 and CK14 respectively. T51B cells also contain vimentin assembled as a network of intermediate filaments distinct from that of the CKs. In the present study, we examined the expression of CK14 gene in various LEC preparations and a Triton-resistant rat skin cytoskeletal fraction, and then assessed its usefulness as an LEC specific marker in the liver. Northern and Western blot analyses with cDNAs and antibodies for CK8, CK14, CK18 and vimentin confirmed that rat hepatocytes express CK8 and CK18 genes only, whereas T51B cells express CK8, CK14 and vimentin genes in the absence of CK18. CK14 was also present in LECs derived as primary from embryonic-day 12 rat liver and secondary cultures from 4-day-old rat liver. Primary cultures of oval cells isolated from 3′-methyl-4-dimethylaminoazobenzene (3′-Me-DAB) treated rat liver (an enriched source of biliary epithelial cells) contained CK14 mRNAs which were slightly shorter than those in LECs. The analyses of CK5 (the usual partner of CK14) gene expression using specific cDNA and antibody clearly demonstrated its absence in LECs. In situ double immunolocalization analyses by laser scanning confocal microscopy showed that CK14 was not present in hepatocytes (HES + 6 cells) and was expressed in some biliary epithelial (BDS 7 + cells). CK14-positive cells were also found in the Glisson's capsule. However, CK14-positive cells of the portal region were vimentin negative, whereas those of the Glisson's capsule were vimentin positive. Our results suggest that CK14 gene expression is part of the differentiation program of two types of LECs and that this differential CK14 gene expression can be used as a new means to type LECs in culture and in vivo.
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down regulation of Cytokeratin 14 mrna in polyoma virus middle t transformed rat liver epithelial cells
Cell Growth & Differentiation, 1992Co-Authors: Isabelle Royal, Richard Blouin, Henriette Gourdeau, Normand MarceauAbstract:We have recently shown that rat liver nonparenchymal epithelial cells, such as T51B cells, selectively express Cytokeratin (CK) 14 as a partner of CK8 in their intermediate filaments, and we proposed CK14 as a unique cell lineage marker of the liver epithelial cell population (R. Blouin, M-J. Blouin, I. Royal, A. Grenier, A. Loranger, D. R. Roop, and N. Marceau, Differentiation, submitted for publication, 1992). In the present study, T51B-261A (spontaneously transformed) and T51B-261B (aflatoxin B1-treated) clones and clones derived from T51B cells transfected with SV40 large T (LT) and polyoma virus middle T (MT) were used to investigate CK gene expression in nontransformed and transformed liver epithelial cells. T51B-261A, T51B-261B, MT-T51B, and LT/MT-T51B clones all grew in calcium-deficient medium and formed colonies in soft agar, whereas LT-T51B clones did not grow at all in either one of these assays. T51B-261A and T51B-261B clones formed small, slow growing tumors when injected into newborn syngenic rats, whereas the MT-T51B and LT/MT-T51B clones produced rapidly forming, large tumors. There was no effect of cell transformation on CK expression, except in the clones expressing MT, where the CK intermediate filaments were completely lost. Analyses of [35S]methionine incorporation into the Triton-resistant cytoskeleton and of total proteins confirmed that CKs were absent. In contrast, vimentin intermediate filaments remained unaffected in all of the clones.(ABSTRACT TRUNCATED AT 250 WORDS)
Peiguo G Chu - One of the best experts on this subject based on the ideXlab platform.
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Cytokeratin 14 immunoreactivity distinguishes oncocytic tumour from its renal mimics an immunohistochemical study of 63 cases
Histopathology, 2001Co-Authors: Peiguo G Chu, Lawrence WeissAbstract:Cytokeratin 14 immunoreactivity distinguishes oncocytic tumour from its renal mimics: an immunohistochemical study of 63 cases Aims: The Cytokeratin 14 (CK14) expression in oncocytomas or oncocytic tumours of various tissue origins has not been established. We have studied CK14 expression in 30 cases of oncocytic tumours of various tissue origins and 33 cases of renal cell carcinoma with overlapping features (mimics) by immunohistochemistry. Methods and results: Immunohistochemistry (ABC–HRP method) was performed for detection of CK14 in 30 cases of oncocytic tumour and 33 cases of renal mimics. To demonstrate CK14 specificity and sensitivity in oncocytic tumours, mES-13 (an anti-mitochondrial monoclonal antibody) immunohistochemistry was also performed in 20 of 30 cases on oncocytic tumour and all 33 cases of renal mimics. We found that all 30 cases of oncocytic tumour showed cytoplasmic CK14 positivity. All 20 cases of oncocytic tumour studied with mES-13 were positive. CK14 immunoreactivity was identified in only four cases of renal cell carcinoma (one conventional renal cell carcinoma with granular cytoplasm and three chromophobe renal cell carcinomas with eosinophilic cytoplasm). In contrast, all 33 cases of renal cell carcinoma were positive for mES-13 to varying degrees. Conclusion: The homogeneous, cytoplasmic, and granular CK14 immunoreactivity is sensitive and specific for oncocytic tumours, whereas CK14 immunoreactivity in renal mimics is light and sporadic with peripheral accentuation.
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Cytokeratin 14 expression in epithelial neoplasms a survey of 435 cases with emphasis on its value in differentiating squamous cell carcinomas from other epithelial tumours
Histopathology, 2001Co-Authors: Peiguo G Chu, Mark H Lyda, Lawrence WeissAbstract:Cytokeratin 14 expression in epithelial neoplasms: a survey of 435 cases with emphasis on its value in differentiating squamous cell carcinomas from other epithelial tumours Aims: The tissue distribution of Cytokeratin 14 (CK14) in epithelial neoplasms is not well defined. We have evaluated 435 cases of epithelial neoplasm of various origins with Cytokeratin 14 monoclonal antibody with special attention to possible use in differential diagnosis. Methods and results: Immunohistochemistry (ABC–HRP method) was performed for detection of CK14. We found that the expression of Cytokeratin 14 was generally restricted to: (i) the majority of cases of squamous cell carcinoma regardless of origin (67/74) and degree of differentiation; (ii) neoplasms with focal squamous differentiation, including endometrial, and ovarian adenocarcinoma, malignant mesothelioma and transitional cell carcinoma; (iii) thymoma (8/8); (iv) myoepithelial components of salivary gland pleomorphic adenoma (3/4); and (v) oncocytic neoplasms, including thyroid Hurthle cell adenoma (1/1) and salivary gland Warthin’s tumour (2/2). Conclusion: CK14 protein is a useful marker in differential diagnosis of squamous cell carcinomas.
