cytokeratin 15

  • 文章类型: Journal Article
    细胞角蛋白15(CK15)已被描述为人体器官中的干细胞标志物,其表达在乳腺组织中可见。CK15表达与子宫内膜癌和食管癌的侵袭性特征相关,但是缺乏乳房数据。本研究旨在探讨CK15在乳腺癌中的临床病理相关性和预后意义。检索了一个多机构的乳腺癌队列。获得临床病理和结果数据,并与免疫组织化学表达CK15和一组生物标志物进行比较。总的来说,包括1476例,表达率为3.5%,在腔亚型中优先表达(p=0.024),其中管腔B癌最高(4.7%),与基底样癌(1%)和HER2过表达癌(0%)相反。除淋巴结分期(p=0.013)和淋巴结转移(p=0.048)外,雌激素(p=0.035)和孕激素受体(p=0.001)阳性,与其他临床病理参数无相关性.在CK15阳性管腔B癌中,观察到乳腺癌特异性生存期(BCSS)较短的趋势(p=0.062)。在腔内BHER2阴性癌的进一步亚组多变量分析中,CK15表达与较短的BCSS(HR=9.004,p=0.001)和无病生存期(HR=7.085,p<0.001)具有强相关性。限于管腔内乳腺癌,特别是腔内BHER2阴性,CK15被证明是较高复发风险和较短生存期的可靠独立预测因子。具有潜在的临床预后标志物和该亚组癌症的唯一干细胞标志物。
    Cytokeratin 15 (CK15) has been described as a stem cell marker in human organs and its expression is seen in breast tissue. CK15 expression is associated with aggressive features in endometrial and oesophageal cancers, but data on the breast are lacking. This study aims to investigate the clinicopathological associations and prognostic significance of CK15 in breast carcinomas. A multi-institute cohort of breast carcinomas were retrieved. Clinicopathological and outcome data were obtained and compared with immunohistochemical expression CK15 and a panel of biomarkers. In total, 1,476 cases were included, with an expression rate of 3.5%, preferentially expressed in luminal subtypes (p=0.024), with luminal B carcinomas being the highest (4.7%), as opposed to basal-like (1%) and HER2-overexpressed carcinomas (0%). Except for nodal stage (p=0.013) and nodal metastasis (p=0.048), oestrogen (p=0.035) and progesterone receptor (p=0.001) positivity, there were no associations with other clinicopathological parameters. A trend was observed with shorter breast cancer specific survival (BCSS) in CK15-positive luminal B carcinomas (p=0.062). On further subgroup multivariate analysis of luminal B HER2-negative carcinomas, CK15 expression exhibited robust correlation with shorter BCSS (HR=9.004, p=0.001) and disease-free survival (HR=7.085, p<0.001). Restricted to luminal breast carcinomas, specifically luminal B HER2-negative, CK15 is demonstrated to be a robust independent predictor of higher risk of recurrence and shorter survival, with potential as a clinical prognostic marker and an exclusive stem cell marker for this subgroup of carcinomas.
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  • 文章类型: Case Reports
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  • 文章类型: Journal Article
    BACKGROUND: Body region-dependent hair follicle (HF) characteristics are concerned with follicular size and distribution, and have been demonstrated to have characteristics for each region of the body.
    OBJECTIVE: The aim of the present study was to investigate the expression patterns of the markers called cytokeratin 15 (K15), cytokeratin 6 (K6) and monoclonal antibody Ki-67, and also apoptosis in HFs, which can be observed in different parts of the human body.
    METHODS: In this study, healthy human HFs were taken by biopsy from 5 various donor sites of the human body: the scalp, the leg, the abdomen, the back and waist. HF-containing skin specimens taken using cryosection were stained with hematoxylin & eosin (H&E) and K15, K6, Ki-67 and terminal deoxynucleotidyl transferase-mediated digoxigenin-dNTP nick end-labelling (TUNEL) immunofluorescence staining protocol was performed.
    RESULTS: Different skin regions from the human body were examined histologically. While the HFs of scalp tissue showed anatomically obvious hair layers, some hair sections from other regions, like the leg, the abdomen, back and waist, were not as distinct as in the scalp region. According to our findings, K15 expression was highest in the scalp. In addition, the immunoreactivity (IR) intensity of K15 was significantly decreased in the HFs on the waist and abdominal regions, compared to the scalp and back regions (p < 0.001). However, the IR intensity of K6 in the scalp region was statistically significantly higher than the IR intensity of K6 in the abdomen region (p < 0.05). Moreover, we showed intraepithelial apoptosis and proliferation of keratinocytes in the bulge of HF. In the study, Ki-67-positive and TUNEL-positive cell numbers were not statistically significant (p > 0.05).
    CONCLUSIONS: Our findings are important for further investigation of molecular aspects of the human hair follicle stem cells compartments in health and disease, which might be a promising model for comparative studies with different human diseases.
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  • 文章类型: Journal Article
    BACKGROUND: Lichen planopilaris (LPP) is a lymphocyte-mediated cicatricial alopecia mostly involving the bulge region of the hair follicle. The origin of LPP is unknown. Therapy for LPP often does not prevent disease progression. We describe histologic and immunohistologic features that aid in diagnosis and provide an explanation for disease progression in LPP.
    OBJECTIVE: We sought to demonstrate a decrease in the number of catagen-/telogen-phase follicles and to confirm the loss of cytokeratin 15 (CK15) expression in the stem cells of LPP-affected follicles.
    METHODS: In all, 144 LPP cases were retrieved; 55 cases were stained immunohistochemically, targeting the CK15 antigen with 40 cases ultimately analyzed for CK15 expression.
    RESULTS: Catagen/telogen phase was significantly decreased or absent in all cases of LPP, a novel clue useful in histologic diagnostics. The loss of CK15+ stem cells in most affected follicles in LPP was also confirmed, with unaffected follicles retaining CK15+ stem cells.
    CONCLUSIONS: Limited tissue for analysis remained in the clinical sample tissue blocks.
    CONCLUSIONS: Damaged follicles that have lost their CK15+ stem cells disappear when they enter catagen phase. CK15+ stem cell loss explains the clinical observation that LPP progresses despite immunosuppressive therapies. Finally, the absence of catagen/telogen hair follicles is a helpful diagnostic clue for LPP.
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  • 文章类型: Journal Article
    OBJECTIVE: The mammalian cytoskeleton is composed in part from keratin filaments which form a complex, highly dynamic intracellular network. We investigate the expression of cytokeratin 15 (CK15) in human endometrium and its regulation by HOXA10 in the human endometrial cell lines.
    METHODS: Endometrial biopsies from throughout the menstrual cycle (N = 32) were evaluated for CK15 protein expression by immunohistochemistry using a mouse monoclonal antibody. The human endometrial epithelial cell line (Ishikawa) was transfected with pcDNA/HOXA10. Total RNA was isolated and quantitative real-time polymerase chain reaction was performed to determine expression levels of CK15.
    RESULTS: In the peri-implantation window (days 16 through 23) CK15 protein expression in glandular epithelium of human endometrium decreased to 50% of proliferative phase expression levels. Expression of CK15 messenger RNA decreased by 99% (P < .05) after pcDNA/HOXA10 transfection of Ishikawa cells. The CK15 expression corresponded to the time of maximal secretory epithelial remodeling.
    CONCLUSIONS: Gene expression of CK15 is decreased in a HOXA10-dependent fashion in human endometrial epithelial cells. Expression decreases in the peri-implantation period concurrent with maximal HOXA10 expression. Dramatic changes in cellular architecture are necessary to achieve the secretory changes in the endometrial epithelium that bring about the implantation window. Alterations in CK15 likely facilitate these cytoskeletal changes, ultimately promoting endometrial receptivity.
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  • 文章类型: Journal Article
    BACKGROUND: Histopathological evaluations can differentiate between clinically resembling trichoepithelioma (TE) and basal cell carcinoma (BCC) unless the biopsy specimens are small or superficial. Previous studies used immunohistochemical evaluation for Bcl-2 and cytokeratin 15 (CK15), in attempts to differentiate between these two entities, with heterogeneous findings.
    OBJECTIVE: This study intended to compare the rate and patterns of Bcl-2 and CK15 expressions between specimens of TE and nodular BCC.
    METHODS: Case-series including formalin-fixed, paraffin-embedded cutaneous biopsies.
    METHODS: Twenty-two BCC and 12 TE specimens were stained for Bcl-2 and CK15 and examined microscopically. The rate and patterns of expressions were compared between the two groups.
    METHODS: Statistical analysis was performed using the statistical software (SPSS version 16.0; SPSS Inc., Chicago, IL, USA), Pearson Chi-square, or Fisher\'s exact tests, wherever appropriate.
    RESULTS: The two groups were comparable for the expression rate and patterns of Bcl-2 (86.4%: 5 central, 14 diffuse in BCC vs. 83.3%: 2 central, 8 diffuse in TE; P = 0.59 and 0.54 for rate and pattern, respectively). The rate of CK15 expression was significantly higher in TE specimens (66.7%: 4 central, 3 diffuse, 1 peripheral vs. 4.5%: 1 central; P < 0.001). The positive likelihood ratio in distinguishing the two neoplasms was 14.7 (95% confidence interval: 2.1-103.7).
    CONCLUSIONS: CK15 but not Bcl-2 staining may help in differentiating between BCC and TE even in BCCs with follicular differentiation.
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