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Nigel P Mongan - One of the best experts on this subject based on the ideXlab platform.
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elevated mmp9 expression in breast cancer is a predictor of shorter patient survival
Breast Cancer Research and Treatment, 2020Co-Authors: Chitra Joseph, Mansour Alsaleem, Nnamdi Orah, Pavan L Narasimha, Islam M Miligy, Sasagu Kurozumi, I O Ellis, Nigel P MonganAbstract:MMP9 is a matricellular protein associated with extracellular matrix (ECM) remodelling, that promotes tumour progression, and modulates the activity of cell adhesion molecules and cytokines. This study aims to assess the prognostic value of MMP9 and its association with cytoskeletal modulators in early-stage invasive breast cancer (BC). MMP9 expression was evaluated by immunohistochemistry using a well-characterised series of primary BC patients with long-term clinical follow-up. Association with clinicopathological factors, patient outcome and ECM remodelling BC-biomarkers were investigated. METABRIC dataset, BC-GenExMiner v4.0 and TCGA were used for the external validation of MMP9 expression. GSEA gene enrichment analyses were used to evaluate MMP9 associated pathways. MMP9 immunopositivity was observed in the stroma and cytoplasm of BC cells. Elevated MMP9 protein levels were associated with high tumour grade, high Nottingham Prognostic Index, and hormonal receptor negativity. Elevated MMP9 protein expression correlated significantly with Cytokeratin 17 (Ck17), Epidermal Growth Factor Receptor (EGFR), proliferation (Ki67) biomarkers, cell surface adhesion receptor (CD44) and cell division control protein 42 (CDC42). Cytoplasmic MMP9 expression was an independent prognostic factor associated with shorter BC-specific survival. In the external validation cohorts, MMP9 expression was also associated with poor patients’ outcome. Transcriptomic analysis confirmed a positive association between MMP9 and ECM remodelling biomarkers. GSEA analysis supports MMP9 association with ECM and cytoskeletal pathways. This study provides evidence for the prognostic value of MMP9 in BC. Further functional studies to decipher the role of MMP9 and its association with cytoskeletal modulators in BC progression are warranted.
Jin Hee Sohn - One of the best experts on this subject based on the ideXlab platform.
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Cytokeratin 17 expression is associated with poor prognosis in gallbladder adenocarcinoma
Applied Immunohistochemistry & Molecular Morphology, 2017Co-Authors: Kyungeun Kim, Hyoun Wook Lee, Seoung Wan Chae, Donghoon Kim, Hyun Joo Lee, Kyuengwhan Min, Jungsoo Pyo, Junho Shin, Jin Hee SohnAbstract:Cytokeratin 17 (CK17), a basal/myoepithelial cell keratin, is a poor prognostic marker for cancers of organs such as the stomach, ovary, and breast as well as a useful diagnostic marker for pancreatobiliary adenocarcinoma. However, its expression pattern and prognostic significance have not been studied in gallbladder adenocarcinoma. We constructed a tissue microarray from samples from 82 consecutive patients with gallbladder adenocarcinoma treated by cholecystectomy at the Kangbuk Samsung Hospital from 2000 to 2011. CK17 expression was examined by immunohistochemistry and correlated with clinicopathologic prognostic factors. CK17 stained the cytoplasm of tumor cells and immunohistochemical interpretation was possible in 77 cases. Among these, 41 (53.2%) were considered positive using a 5% cutoff determined by a receiver operating characteristic curve (area under the curve=0.656, P=0.021). CK17 expression was associated with poor tumor differentiation (P<0.001), high pT stage (P<0.001), presence of distant metastasis (P=0.036), and low disease-specific survival rate (P<0.001). These results indicate that CK17 can be used as a marker for poor prognosis for gallbladder adenocarcinoma.
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overexpression of Cytokeratin 17 is associated with the development of papillary thyroid carcinoma and the presence of lymph node metastasis
International Journal of Clinical and Experimental Pathology, 2015Co-Authors: Hyun Soo Kim, Kyungeun Kim, Seoung Wan Chae, Donghoon Kim, Jeong Ju Lee, Jin Hee SohnAbstract:Cytokeratin 17 (CK17), a basal/myoepithelial cell keratin, appears to play an important role in the progression of several human malignancies. Increased CK17 expression has previously described in cases of papillary thyroid carcinoma (PTC). However, no studies to date have investigated the clinical significance of CK17 expression in patients with PTC. The aim of this study was to compare the expression of CK17 in patients with PTC with that observed in normal thyroid tissue and benign thyroid lesions, and to examine the relationship between CK17 expression and clinicopathologic characteristics of patients with PTC. CK17 protein expression was evaluated by immunohistochemistry on tissue microarrays containing thyroid tissue samples from 108 PTCs, 16 nodular goiters, and 81 healthy controls. Sixty-five of the 108 (60.2%) PTC tissue samples exhibited positive CK17 expression, whereas all nodular goiters and normal thyroid tissue samples showed a complete absence of CK17 immunoreactivity. The difference in frequency of CK17 positivity between PTC (65/108, 60.2%), normal thyroid tissue (0/81, 0.0%), and benign thyroid lesions (0/16, 0.0%) was statistically significant (P<0.001). Positive CK17 expression in PTC was significantly associated with the presence of lymph node metastasis (P=0.024) and higher pN stage (P=0.028). Expression of CK17 is significantly increased in cases of PTC compared to normal tissue and benign thyroid lesions, and CK17 overexpression is associated with the presence of lymph node metastasis in patients with PTC. These findings suggest that CK17 is involved in the development and metastasis of PTC.
Mansour Alsaleem - One of the best experts on this subject based on the ideXlab platform.
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elevated mmp9 expression in breast cancer is a predictor of shorter patient survival
Breast Cancer Research and Treatment, 2020Co-Authors: Chitra Joseph, Mansour Alsaleem, Nnamdi Orah, Pavan L Narasimha, Islam M Miligy, Sasagu Kurozumi, I O Ellis, Nigel P MonganAbstract:MMP9 is a matricellular protein associated with extracellular matrix (ECM) remodelling, that promotes tumour progression, and modulates the activity of cell adhesion molecules and cytokines. This study aims to assess the prognostic value of MMP9 and its association with cytoskeletal modulators in early-stage invasive breast cancer (BC). MMP9 expression was evaluated by immunohistochemistry using a well-characterised series of primary BC patients with long-term clinical follow-up. Association with clinicopathological factors, patient outcome and ECM remodelling BC-biomarkers were investigated. METABRIC dataset, BC-GenExMiner v4.0 and TCGA were used for the external validation of MMP9 expression. GSEA gene enrichment analyses were used to evaluate MMP9 associated pathways. MMP9 immunopositivity was observed in the stroma and cytoplasm of BC cells. Elevated MMP9 protein levels were associated with high tumour grade, high Nottingham Prognostic Index, and hormonal receptor negativity. Elevated MMP9 protein expression correlated significantly with Cytokeratin 17 (Ck17), Epidermal Growth Factor Receptor (EGFR), proliferation (Ki67) biomarkers, cell surface adhesion receptor (CD44) and cell division control protein 42 (CDC42). Cytoplasmic MMP9 expression was an independent prognostic factor associated with shorter BC-specific survival. In the external validation cohorts, MMP9 expression was also associated with poor patients’ outcome. Transcriptomic analysis confirmed a positive association between MMP9 and ECM remodelling biomarkers. GSEA analysis supports MMP9 association with ECM and cytoskeletal pathways. This study provides evidence for the prognostic value of MMP9 in BC. Further functional studies to decipher the role of MMP9 and its association with cytoskeletal modulators in BC progression are warranted.
Amna Riaz Khan - One of the best experts on this subject based on the ideXlab platform.
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diagnostic utility of Cytokeratin 13 and Cytokeratin 17 in oral epithelial dysplasia and oral squamous cell carcinoma
Asian Pacific Journal of Cancer Biology, 2020Co-Authors: Maryam Nazir Kiani, Muhammad Asif, Fakeha Meraj Ansari, Nighat Ara, Muhammad Ishaque, Amna Riaz KhanAbstract:Objective: To determine the immunohistochemical expression of CK 13 and CK 17 in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma. Methods: A total of 170 cases were retrieved from record files of Histopathology Department, to conduct a cross sectional study at Armed Forces Institute of Pathology, Rawalpindi, over a period of one year from June 2018 to June 2019 along with their formalin-fixed, paraffin embedded blocks comprising 85 cases of each oral squamous cell carcinoma and oral epithelial dysplasia. Blocks were trimmed and cut into very thin sections of 5 microns using microtome and mounted on slides. Tissue mounted slides were stained with routine haematoxylin and eosin followed by immunohistochemical staining of Cytokeratin 13 and Cytokeratin 17. New histological diagnosis of each case was made. Mean and standard deviation were calculated for quantitative variables. Frequency and percentages were calculated for qualitative variables. Chi-square test was employed to assess the significance of difference. The P-value <0.05 was considered significant. Results: In this study, 101 (59.4%) male and 69 (40.6%) female patients with the mean age of 60.63 ± 13.814 (mean ± SD) were collected and buccal mucosa was the most common site of presentation. In a total of 170 cases, 34 (20%) cases showed positive expression of Cytokeratin 13 whereas 136 (80%) cases showed negative expression of Cytokeratin 13. In comparison, out of 170 cases, 133 (78.2%) cases showed positive expression of Cytokeratin 17 whereas 37 (21.8%) cases showed negative expression of Cytokeratin 17. The P-value was found to be < 0.001 and 0.001 for expression of Cytokeratin 13 and Cytokeratin 17 respectively. Conclusion: Opposite expression of Cytokeratin 13 and Cytokeratin 17 was seen in this study, in the form of loss of Cytokeratin 13 and over expression of Cytokeratin 17 with increase in the degree of dysplasia and invasive carcinoma. Correct assessment, diagnosis and management with the help of these markers can lead to early diagnosis and favorable treatment outcome.
Senada Koljenovic - One of the best experts on this subject based on the ideXlab platform.
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evaluation of immunohistochemical markers ck17 and sox2 as adjuncts to p53 for the diagnosis of differentiated vulvar intraepithelial neoplasia dvin
Pharmaceuticals policy and law, 2021Co-Authors: Shatavisha Dasgupta, Folkert J Van Kemenade, Helena C Van Doorn, Senada Koljenovic, Thierry P P Van Den Bosch, Sigrid M A Swagemakers, Nick M A Van Der Hoeven, Ronald Van Marion, Peter J Van Der Spek, Patricia C EwinggrahamAbstract:Histological diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN), the precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC), can be challenging, as features of dVIN may mimic those of non-dysplastic dermatoses. To aid the diagnosis, p53-immunohistochemistry (IHC) is commonly used, and mutant expression patterns are used to support a histological diagnosis of dVIN. However, a proportion of dVIN can show wild-type p53-expression, which is characteristic of non-dysplastic dermatoses. Furthermore, recent research has identified a novel precursor of HPV-independent VSCC-the p53-wild-type differentiated exophytic vulvar intraepithelial lesion (de-VIL). Currently, there are no established diagnostic IHC-markers for p53-wild-type dVIN or de-VIL. We evaluated IHC-markers, Cytokeratin 17 (CK17), and SRY-box 2 (SOX2), as diagnostic adjuncts for dVIN. For this, IHC-expression of CK17, SOX2, and p53 was studied in dVIN (n = 56), de-VIL (n = 8), and non-dysplastic vulvar tissues (n = 46). For CK17 and SOX2, the percentage of cells showing expression, and the intensity and distribution of expression were recorded. We also performed next generation targeted sequencing (NGTS) on a subset of dVIN (n = 8) and de-VIL (n = 8). With p53-IHC, 74% of dVIN showed mutant patterns and 26% showed wild-type expression. Median percentage of cells expressing CK17 or SOX2 was significantly higher in dVIN (p53-mutant or p53-wild-type) and de-VIL than in non-dysplastic tissues (p < 0.01). Diffuse, moderate-to-strong, full epithelial expression of CK17 or SOX2 was highly specific for dVIN and de-VIL. With NGTS, TP53 mutations were detected in both dVIN and de-VIL. We infer that immunohistochemical markers CK17 and SOX2, when used along with p53, may help support the histological diagnosis of dVIN.
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differentiated vulvar intraepithelial neoplasia dvin the most helpful histological features and the utility of Cytokeratins 13 and 17
Virchows Archiv, 2018Co-Authors: Shatavisha Dasgupta, Patricia C Ewinggraham, Folkert J Van Kemenade, Helena C Van Doorn, Vincent Noordhoek Hegt, Senada KoljenovicAbstract:Differentiated vulvar intraepithelial neoplasia (dVIN) is the precursor lesion of HPV-negative vulvar squamous cell carcinoma (VSCC). The histopathological diagnosis of dVIN can be challenging, as it often resembles vulvar non-neoplastic epithelial disorders (NNED), especially lichen sclerosus (LS). We aimed to establish the most specific and reproducible histological features of dVIN and assessed Cytokeratin 13 (CK13) and Cytokeratin 17 (CK17) immunohistochemistry as a diagnostic aid. Consecutive cases of dVIN (n = 180) and LS (n = 105) from the period 2010 to 2013 were reviewed using a checklist of histological features. Each feature was recorded as ‘present’ or ‘absent’ and statistical comparison (dVIN vs LS) was made. Interobserver agreement between two pairs of pathologists was assessed for a subset of cases of dVIN (n = 31) and LS and other NNED (n = 23). Immunohistochemistry with CK13, CK17, MIB1 and p53 was performed on dVIN, LS, and other NNED cases. Macronucleoli, features of disturbed maturation and angulated nuclei were significantly more common in dVIN than LS (p < 0.001). We found ‘substantial agreement’ for the diagnosis of dVIN (κ = 0.71). Macronucleoli and deep keratinisation had the highest agreement. In dVIN, the mean percentage of cells staining with CK13 was 15 and with CK17, this was 74. For LS, the mean percentage of cells staining with CK13 was 31, and with CK17, this was 41. By plotting receiver operating characteristic curves (ROC), an area under the curve (AUC) of 0.52 was obtained for CK13, and an AUC of 0.87 was obtained for CK17. The most helpful histological features for diagnosing dVIN were macronucleoli, features of disturbed maturation, and angulated nuclei. Increased CK17 expression may have promise for supporting dVIN diagnosis.
