Expression Of High Molecular Weight Cytokeratins Research Articles

Role of Two Antibodies Panel High Molecular Weight Cytokeratin and Alpha-MethylacylCoA Racemase in Diagnosing Prostatic Lesions: A Cross-sectional Study

Introduction: Prostatic diseases cause significant morbidity and mortality. Although histopathological examination is the gold standard for diagnosing prostatic lesions but diagnosis may be challenging in the presence of benign mimickers or a very small focus of malignancy. Immunohistochemical aid to morphology helps in making a timely and accurate diagnosis. Aim: This study was done to evaluate the role of two antibodies panel High Molecular Weight Cytokeratin (HMWCK) and AlphaMethylacyl-CoA Racemase (AMACR) in improving the diagnostic accuracy of prostatic lesions. Materials and Methods: This was an observational cross-sectional study conducted in the Department of Pathology, Shri Guru Ram Rai Institute of Medical and Health Sciences (SGRRIM and HS), Dehradun, Uttarakhand, India, from May 2019 to October 2020. Haemotoxylin and Eosin (H&E) stained sections of prostatic biopsies were classified into benign and malignant. Amongst malignant lesions, prostatic adenocarcinomas were graded according to Gleason’s grading system and Gleason’s scores were noted. One section from each was subjected to AMACR and HMWCK antibody tests. HMWCK was interpreted as negative/positive and continuous/ discontinuous. For AMACR, both location and intensity of stain was observed. The parameters studied were Gleason’s score, group grade, expression of HMWCK and AMACR. Categorical data was presented in form of frequency and percentage. Independent t-test, Yates Chi-square test were used. Data was entered in Microsoft (MS) Excel sheet and analysis was done using CRAN R 2.1. Results: Total of 80 prostatic biopsies were taken, 24 were malignant and 55 were benign and one was Benign Prostatic Hyperplasia (BPH) with a focus suspicious for malignancy showing atypical small acinar proliferation on histopathological examination. The mean age of non neoplastic cases was 67.68±8.56 years, while that of neoplastic lesions was 75.41±9.34 years. Amongst benign, 56.3% (31/55) cases were BPH, 43.6% (24/55) cases were BPH with associated lesions which included 62.5% (15/24) cases of BPH with non specific prostatitis; 29.2% (7/24) cases of BPH with adenosis and 8.3% (02/24) cases of BPH with basal cell hyperplasia. Of malignant cases, 24 cases were of adenocarcinoma with maximum cases having Gleason’s score 9 (11/24;45.8%) and Group grade V (18/24;75%). The sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) of HMWCK and AMACR were calculated using histopathology as the gold standard. Conclusion: Although histopathology is the gold standard in prostatic biopsies but immunohistochemistry is additional diagnostic aid in confirmation of diagnosis. Immunohistochemistry not only confirms the histological diagnosis but is of great help in challenging cases. It has markedly increased the diagnostic accuracy

Cytokeratin Expression in Gastrointestinal Stromal Tumor

Gastrointestinal stromal tumor is the most common clinically significant mesenchymal neoplasm of the gastrointestinal tract. The expression of the intermediate filament cytokeratin in gastrointestinal stromal tumor is not frequently reported in the literature. The aim of this study was to investigate the immunohistochemical expression of several types of cytokeratin in a large number of cases (n=687), including a pan-cytokeratin marker (AE1/AE3 cocktail antibodies), high-molecular weight cytokeratins (34ßE12 antibody), and individual cytokeratins 8 (35ßH11 and CAM5.2 antibodies), 7, 14, and 20. Ki-67 antigen was used for the determination of cell proliferation index, and the correlation between Ki-67 and cytokeratin expression was evaluated. Cytokeratin expression was also correlated with several clinicopathologic parameters. The expression of pan-cytokeratin was observed in 24 (3.5%) cases, with variable intensity. Only 1 of 687 (0.1%) cases showed cytokeratin 14 expression. All 687 cases revealed no expression of high-molecular weight cytokeratins, cytokeratins 7, 8, and 20. No significant statistical association was found between AE1/AE3 immunoreactivity and several clinicopathologic parameters, including sex, tumor location and size, cell morphology, mitotic count, risk of aggressive behavior, and Ki-67 antigen cell proliferation index. However, statistical correlation between AE1/AE3 immunoreactivity and a higher age at diagnosis was detected. These results show that cytokeratin expression is not frequent in gastrointestinal stromal tumor, but caution is necessary to avoid erroneous diagnoses.

Basal carcinoma of the breast revisited: an old entity with new interpretations

The introduction of global gene expression analysis in breast cancer research has focused attention onto a repeatedly described subgroup of invasive breast cancer, the basal-like carcinomas. This subgroup is characterised...

Myoepithelial cells in solid variant of intraductal papillary carcinoma of the breast: a potential diagnostic pitfall and a proposal of an immunohistochemical panel in the differential diagnosis with intraductal papilloma with usual ductal hyperplasia

We examined myoepithelial status in intraductal papillary carcinoma (IPC) along with the expression of high-molecular weight cytokeratin (HMWK) and neuroendocrine markers, with special reference to the differential diagnosis of solid intraductal papillary carcinoma(SIPC) and intraductal papilloma with usual ductal hyperplasia (IP-UDH). Twenty-six (93%) of the twenty-eight intraductal papillomas (IP) had myoepithelial cells in >70% of the epithelial-stromal interface of the intraluminal proliferating component. Six (29%) of twenty-one SIPC had almost complete myoepithelial layer like IP-UDH at the epithelial-stromal interface. HMWK (34 beta E-12) was diffusely positive in 14 (93%) of 15 IP-UDH, but 16 (76%) of 21 SIPC were completely negative for HMWK. Neuroendocrine markers were positive in 14 (67%) of SIPC, but all 28 IPs were completely negative. If only the presence of myoepithelial cells is emphasized as a benign hallmark, about 30% of SIPCs may be underdiagnosed as IP-UDH. However, by using a combination of myoepithelial markers, HMWK, and neuroendocrine markers, all of the 36 solid intraductal papillary lesions were properly classified as benign and malignant. Solid intraductal papillary lesions meeting at least two of the following criteria are highly likely to be malignant: (1) absence of myoepithelial cells(<10% of epithelial-stromal interface of intraluminal proliferating component), (2) negative HMWK(<10%), (3) positive neuroendocrine markers (>10%).

PPARgamma ligands suppress proliferation of human urothelial basal cells in vitro.

Expression of peroxisome proliferator-activated receptor (PPAR) gamma in the human urinary tract through embryonic development suggests its possible roles in the development, proliferation, and differentiation of uroepithelium. Little is known, however, about physiological roles of PPARgamma in the urinary tract. We investigated effects of PPARgamma ligands on the proliferation of normal human urothelial cells and stromal cells cultivated from surgical specimens. Active proliferation in vitro as well as high molecular weight cytokeratin expression indicated that cultured urothelial cells possess basal cell phenotype. PPARgamma protein, expressed predominantly in the epithelial layer of the normal human urinary tract in vivo, was abundantly expressed in urothelial cells but barely detectable in stromal cells in vitro. Natural ligand for PPARgamma, 15-deoxy-Delta(12,14) prostaglandin J(2) (15d-PGJ(2)), as well as synthetic ones, troglitazone and pioglitazone, suppressed proliferation of the urothelial cells dose-dependently. These effects were PPARgamma specific because clofibrate or PGF(2alpha) did not affect proliferation of urothelial cells. Neither 9-cis retinoic acid or all-trans retinoic acid (ATRA) at 1 microM showed any synergism on the antiproliferative effects of PPARgamma ligands. Urothelial cells treated with PPARgamma ligands showed drastic morphologic changes and cell cycle arrest at G0/G1 phase accompanied with increased mRNA level of a cyclin-dependent kinase inhibitor p21(WAF1/CIP1). Since 15d-PGJ(2) is present in vivo during the resolution phase of inflammation, these results indicated that PPARgamma might be involved in the terminal phase of urothelial re-epithelialization processes.

Immunohistochemical analysis of gynecologic tumors.

Ancillary techniques such as immunohistochemistry (IHC) enable the surgical pathologist to extract additional information from fixed, deparaffinized tissue specimens and to provide data critical to optimal clinical management of the patient. In this review of applications of IHC to the analysis of gynecologic malignancies, the usefulness of immunohistochemical analysis of neoplasms of the cervix, endometrium, and ovary is summarized. In the uterine cervix, dysplasia is associated with qualitative and quantitative alterations in the expression of the Ki-67 antigen expression, as well as an ability to detect human papillomavirus. Endometrial endometrioid adenocarcinomas display a highly characteristic immunophenotype, with coexpression of cytokeratin and vimentin and demonstration of foci of high molecular weight cytokeratin expression; in addition, IHC analysis of estrogen and progesterone receptor and p53 expression can provide important prognostic information about this tumor. Stromal tumors of the endometrium may display a partial smooth muscle immunophenotype, but novel markers such as CD10 provide new tools for the identification of these tumors. The immunophenotypes of the normal ovarian surface epithelium (OSE) and corresponding tumors display significant overlap with, but important distinctions from, mesothelium, and important new markers such as the Wilms tumor gene product can prove useful in the identification of carcinomas of the OSE. Important prognostic markers for carcinomas of the OSE include the HER-2/neu gene product and p53, alterations of which can both be assessed by IHC techniques. Finally, the recent availability of markers of ovarian stroma, including Melan-A and inhibin-alpha, has provided a means for the positive identification of ovarian stromal tumors, which can manifest protean histological appearances.

Hydrocortisone Increases the Numbers of KL1+Cells, a Discrete Thymic Epithelial Cell Subset Characterized by High Molecular Weight Cytokeratin Expression

The thymic epithelium, a major component of the thymic microenvironment, is a heterogeneous tissue bearing distinct monoclonal antibody-defined subsets. Among these, KL1+ cells represent a mouse medullary subpopulation characterized by high mol wt cytokeratin expression. Given the fact that thymic epithelial cells (TEC) express glucocorticoid receptors and that glucocorticoid hormones are known to modulate the expression of keratins, we decided to study the in vivo effects of hydrocortisone on KL1+ cells in normal and autoimmune mice. Within 24 h after a single injection of this steroid we observed a significant increase in the number of KL1+ cells. Interestingly, this effect was reversible and was no longer detected 7 days after treatment. Parallel studies analyzing the effects of hydrocortisone on the secretion of thymulin, a chemically defined thymic hormone revealed a transient decrease in serum levels of this hormone, but with different kinetics than the effects on KL1+ cells. Ontogenetic studies showed that the responsiveness of TEC to hydrocortisone, in terms of high mol wt cytokeratin expression, appeared late in fetal life and disappeared in aging animals. Importantly, aging, but also young adult, autoimmune mice were not responsive. In vitro experiments using a mouse TEC line confirmed the data observed in vivo demonstrating that the increase in KL1+ cells is a direct effect of hydrocortisone on TEC. The bulk of the data presently reported demonstrates that glucocorticoid hormone can act on TEC modulating the expression of both secretory and cytoskeletal protein families.