scholarly journals Expression of hnRNPK & Claudin-4 in HCV-Induced Early HCC and Adjacent Liver Tissue

2017 ◽  
Vol 5 (5) ◽  
pp. 595-602
Author(s):  
Olfat Hammam ◽  
Mona Magdy ◽  
Amgad Anas ◽  
Ali Abdel Rahim ◽  
Mohamed Heedaya ◽  
...  
Keyword(s):  
Liver Tissue ◽  
Epithelial Mesenchymal Transition ◽  
Low Grade ◽  
High Grade ◽  
Fibrosis Score ◽  
Immunohistochemical Expression ◽  
Mesenchymal Transition ◽  
Curative Therapy ◽  
Egyptian Patients ◽  
Early Hcc

BACKGROUND: HCC in Egypt usually occurs in HCV cirrhotic livers with poor prognosis due to late diagnosis. High hnRNPK & low Claudin-4 profiles indicate Epithelial Mesenchymal Transition (EMT), malignant transformation and high-grade tumours.AIM: We studied the immunohistochemical expression of hnRNPK and Claudin-4 in HCV induced early HCC (eHCC) and adjacent liver tissue in Egyptian patients to improve eHCC detection in cirrhotic livers with better curative therapy options.METHOD: We studied the immunohistochemical expression of hnRNPK and Claudin-4 in 100 Egyptian patients resection specimens of HCV induced early HCC (eHCC) and adjacent liver tissue, in order to improve eHCC detection in cirrhotic livers, thus improving their therapeutic options.RESULTS: Early HCC grade significantly directly correlated with nuclear hnRNPK/5HPFs count and inversely correlated with Claudin-4 expression %, with a converse correlation between hnRNPK and Claudin-4. Moreover in eHCC, combined hnRNPK ³ 30/5HPFs & Claudin-4 ³ 40% significantly distinguished low grade eHCC (G1) from high grade eHCC (G2&G3), with sensitivity 97% & specificity 69.7% for hnRNPK ³ 30/5HPFs, and with sensitivity 70% & specificity 94.3% for Claudin-4 ³ 40%. Moreover in the adjacent liver, both markers expressions significantly directly correlated with each other and with METAVIR fibrosis score but not with activity. Furthermore, 58% of eHCCs showed hnRNPK ³ 30 Claudin-4 < 40% profile, indicating EMT type3, compared to 26% with hnRNPK ³ 30 Claudin-4 £ 10% profile in adjacent cirrhotic/ precirrhotic liver, with significant use of combined hnRNPK ³30/5HPFs & Claudin 4 £ 10% as eHCC prediction cut offs in cirrhosis (p < 0.05).CONCLUSION: Combination of hnRNPK and Claudin-4 can indicate early HCC development in HCV cirrhotic livers using hnRNPK ³ 30/5HPFs & Claudin-4 £ 10% cut offs. Also, combination of hnRNPK ³ 30/5HPFs & Claudin-4 ³ 40% can distinguish low grade eHCC (G1) from high grade eHCC (G2&G3).

scholarly journals Pancreatic Cancers with High Grade Tumor Budding Exhibit Hallmarks of Diminished Anti-Tumor Immunity

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1090
Author(s):  
Hassan Sadozai ◽  
Animesh Acharjee ◽  
Thomas Gruber ◽  
Beat Gloor ◽  
Eva Karamitopoulou
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Disease Progression ◽  
Immune Escape ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Budding ◽  
Ductal Adenocarcinoma ◽  
Low Grade ◽  
High Grade ◽  
Mesenchymal Transition

Tumor budding is associated with epithelial-mesenchymal transition and diminished survival in a number of cancer types including pancreatic ductal adenocarcinoma (PDAC). In this study, we dissect the immune landscapes of patients with high grade versus low grade tumor budding to determine the features associated with immune escape and disease progression in pancreatic cancer. We performed immunohistochemistry-based quantification of tumor-infiltrating leukocytes and tumor bud assessment in a cohort of n = 111 PDAC patients in a tissue microarray (TMA) format. Patients were divided based on the ITBCC categories of tumor budding as Low Grade (LG: categories 1 and 2) and High Grade (HG: category 3). Tumor budding numbers and tumor budding grade demonstrated a significant association with diminished overall survival (OS). HG cases exhibit notably reduced densities of stromal (S) and intratumoral (IT) T cells. HG cases also display lower M1 macrophages (S) and increased M2 macrophages (IT). These findings were validated using gene expression data from TCGA. A published tumor budding gene signature demonstrated a significant association with diminished survival in PDAC patients in TCGA. Immune-related gene expression revealed an immunosuppressive TME in PDAC cases with high expression of the budding signature. Our findings highlight a number of immune features that permit an improved understanding of disease progression and EMT in pancreatic cancer.

scholarly journals Exosome-Derived LINC00960 and LINC02470 Promote the Epithelial-Mesenchymal Transition and Aggressiveness of Bladder Cancer Cells

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1419
Author(s):  
Cheng-Shuo Huang ◽  
Jar-Yi Ho ◽  
Jung-Hwa Chiang ◽  
Cheng-Ping Yu ◽  
Dah-Shyong Yu
Keyword(s):  
Bladder Cancer ◽  
Notch Signaling ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Low Grade ◽  
High Grade ◽  
Mesenchymal Transition ◽  
Bladder Cancer Cells

Exosomes are essential for several tumor progression-related processes, including the epithelial–mesenchymal transition (EMT). Long non-coding RNAs (lncRNAs) comprise a major group of exosomal components and regulate the neoplastic development of several cancer types; however, the progressive role of exosomal lncRNAs in bladder cancer have rarely been addressed. In this study, we identified two potential aggressiveness-promoting exosomal lncRNAs, LINC00960 and LINC02470. Exosomes derived from high-grade bladder cancer cells enhanced the viability, migration, invasion and clonogenicity of recipient low-grade bladder cancer cells and activated major EMT-upstream signaling pathways, including β-catenin signaling, Notch signaling, and Smad2/3 signaling pathways. Nevertheless, LINC00960 and LINC02470 were expressed at significantly higher levels in T24 and J82 cells and their secreted exosomes than in TSGH-8301 cells. Moreover, exosomes derived from LINC00960 knockdown or LINC02470 knockdown T24 cells significantly attenuated the ability of exosomes to promote cell aggressiveness and activate EMT-related signaling pathways in recipient TSGH-8301 cells. Our findings indicate that exosome-derived LINC00960 and LINC02470 from high-grade bladder cancer cells promote the malignant behaviors of recipient low-grade bladder cancer cells and induce EMT by upregulating β-catenin signaling, Notch signaling, and Smad2/3 signaling. Both lncRNAs may serve as potential liquid biomarkers for the prognostic surveillance of bladder cancer progression.

Role of the Immunohistochemical ZEB1 Expression in Uterine Mesenchymal Neoplasms

2022 ◽  
pp. 106689692110701
Author(s):  
Murat Çelik ◽  
Zeliha Esin Çelik
Keyword(s):  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Endometrial Stromal Sarcoma ◽  
Therapy Resistance ◽  
Low Grade ◽  
High Grade ◽  
Diagnostic Challenge ◽  
Mesenchymal Tumors ◽  
Mesenchymal Transition ◽  
Mesenchymal Neoplasms

The distinction of mesenchymal tumors of the uterus is a frequent diagnostic challenge in gynecologic pathology. Especially, distinguishing low-grade endometrial stromal sarcoma (ESS) from leiomyoma or distinguishing low-grade ESS from high-grade ESS can be difficult. Epithelial-mesenchymal transition (EMT) is a physiological and pathological process in which epithelial cells lose their morphological features, become elongated and acquire mesenchymal traits. The signaling pathway of Zinc finger E-box binding homeobox 1 (ZEB1) is one of the most significant pathways involved in the EMT process and it has a crucial role in cancer progression, metastasis, and therapy resistance. We studied a series of 69 uterine mesenchymal neoplasms including 18 endometrial stromal sarcomas (10 cases of low grade and 8 cases of high grade endometrial stromal sarcomas), 26 leiomyosarcomas (8 cases of grade 1 and 19 cases of grade 2-3 leiomyosarcomas), 15 leiomyomas, and 10 rhabdomyosarcomas, using an antibody ZEB1. We graded the leiomyosarcomas depending on the FNCLCC grading system. It was observed that leiomyosarcoma was more intensely stained with ZEB1 than leiomyoma (P < 0.001) and high-grade ESS was significantly more intensely stained with ZEB1 protein than low-grade ESS (P < 0.004). It also was observed that high-grade leiomyosarcoma was significantly more intensely stained with ZEB1 protein than low-grade leiomyosarcoma (P < 0.000). Our data suggest that Zeb1 can be used to differentiate high-grade sarcomas from their low-grade counterparts as well as benign and malignant smooth muscle tumors of the uterus.

scholarly journals Exosome-transmitted LINC00960 and LINC02470 promote the epithelial-mesenchymal transition and aggressiveness of bladder cancer cells

2020 ◽  
Author(s):  
Cheng-Shuo Huang ◽  
Jar-Yi Ho ◽  
Jung-Hwa Chiang ◽  
Cheng-Ping Yu ◽  
Dah-Shyong Yu
Keyword(s):  
Bladder Cancer ◽  
Notch Signaling ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Low Grade ◽  
High Grade ◽  
Mesenchymal Transition ◽  
Bladder Cancer Cells

Abstract Background Exosomes are essential for several tumor progression-related processes, including epithelial-mesenchymal transition (EMT). Long noncoding RNAs (lncRNAs) comprise a major group of exosomal components and regulate the neoplastic development of several cancer types; however, the progressive roles of exosomal lncRNAs in bladder cancer have rarely been addressed. In this study, we identified two potential aggressiveness-promoting exosomal lncRNAs, LINC00960 and LINC02470; we found that these lncRNAs potently induced EMT during bladder cancer progression. Methods Low-grade bladder cancer cells (TSGH-8301) were treated with conditioned media or exosomes derived from high-grade bladder cancer cells (T24 or J82), and the aggressiveness-promoting effects were evaluated. Cell viability, cell migratory/invasive activities and clonogenicity were compared to assess the response to these intercellular transmissions. Exosome-transmitted lncRNA candidates were screened with bioinformatic pipelines, and their expression levels were validated in bladder cancer cells and exosomes. Two novel lncRNAs, LINC00960 and LINC02470, were selected, and their roles and regulatory mechanisms in inducing the aggressiveness of bladder cancer cells were investigated. Results Exosomes derived from high-grade bladder cancer cells enhanced the viability, migration, invasion and clonogenicity of recipient low-grade bladder cancer cells and activated major EMT-upstream signaling pathways, including β-catenin signaling, Notch signaling, and Smad2/3 signaling pathways. Nevertheless, LINC00960 and LINC02470 were expressed at significantly higher levels in T24 and J82 cells and their secreted exosomes than in TSGH-8301 cells. Moreover, exosomes derived from LINC00960 knockdown or LINC02470 knockdown T24 cells significantly attenuated the ability of exosomes to promote cell aggressiveness and activate EMT-related signaling pathways in recipient TSGH-8301 cells. Conclusion Our findings indicate that exosome-transmitted LINC00960 and LINC02470 from high-grade bladder cancer cells promotes the malignant behaviors of recipient low-grade bladder cancer cells and induces EMT by upregulating β-catenin signaling, Notch signaling, and Smad2/3 signaling. Both lncRNAs may serve as potential liquid biomarkers for the prognostic surveillance of bladder cancer progression.

scholarly journals O39: THE HISTOPATHOLOGICAL AND MOLECULAR FEATURES OF BREAST CARCINOMA WITH HIGH-GRADE TUMOUR BUDDING

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
A Lloyd ◽  
E Ryan ◽  
M Boland ◽  
S Medani ◽  
Abd Elwahab ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Lymph Node Involvement ◽  
Low Grade ◽  
High Grade ◽  
Prognostic Variables ◽  
Mesenchymal Transition ◽  
Molecular Features ◽  
Newcastle Ottawa Scale ◽  
Tumour Budding

Abstract Background Tumour budding (TB) is an adverse histological feature in many cancers. It is thought to represent epithelial-to-mesenchymal transition, a key step in the metastatic process. The role of TB in breast carcinoma (BC) remains unclear. Aim To investigate the relationship between TB and other histological and molecular features of BC. Method A systematic search was performed to identify studies that compared features of BC based on the presence or absence of high-grade TB. Dichotomous variables were pooled as odds ratios (OR) using the Cochran–Mantel–Haenszel method. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale (NOS). Result Seven studies with a total of 1040 patients (high grade TB n=519, 49.9%; low grade TB n=521, 50.1%) were included. A moderate- to high-risk of bias was noted. The median NOS was 7 (range 6-8). High-grade TB was significantly associated with lymph node involvement (OR 2.28, 95% c.i. 1.74 to 2.98, P&lt;0.001) and lymphovascular invasion (OR 3.08, 95% c.i. 2.13 to 4.47, P&lt;0.001). Regarding molecular subtypes, there was an increased likelihood of high-grade TB in oestrogen- (OR 1.66, 95% c.i. 1.21 to 2.29, P=0.002) and progesterone-receptor positive (OR 1.68, 95% c.i. 1.10 to 2.59, P=0.02) tumours. In contrast triple negative breast cancer had a reduced incidence of high-grade TB (OR 0.46, 95% c.i. 0.30 to 0.72, P=0.0006). Conclusion High-grade TB is enriched in hormone-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic processes of luminal BC. Take-home message High-grade TB is enriched in hormone-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic processes of luminal BC.

scholarly journals MISMATCH REPAIR PROTEINS AND SURVIVIN IN ADENOMATOUS COLON POLYPS WITH LOW GRADE AND HIGH GRADE DYSPLASIA: AN IMMUNOHISTOCHEMICAL STUDY. Las proteínas para la reparación de desajustes y survivin en pólipos adenomatosos de colon con displasias de bajo y a

2018 ◽  
Vol 10 (3) ◽  
pp. 98-111
Author(s):  
Marian Adamkov ◽  
Desanka Výbohová ◽  
Slávka Drahošová ◽  
Štefan Galbavý
Keyword(s):  
Mismatch Repair ◽  
Survivin Expression ◽  
High Grade Dysplasia ◽  
Low Grade ◽  
Colon Polyps ◽  
High Grade ◽  
Immunohistochemical Expression ◽  
Significant Relation ◽  
Colon Adenomas ◽  
Mismatch Repair Proteins

Objective: The aim of our study was to observe the immunohistochemical expression pattern of mismatch repair proteins (MMRP) MLH1, MSH2, MSH6 and PMS2, as well as survivin, in colon polyps. Methods: We assessed above mentioned proteins in a unified group of 124 tubular adenomatous colon polyps with regard to the presence of dysplastic abnormalities in order to explore their relationship. Furthermore, we studied their relation to such clinicomorphological parameters as the age of patients, size of adenoma, degree of dysplastic changes and localization of the lesion. Results: Survivin was expressed in 97 cases (78.2%), MLH1 was found in 111 cases (89.5%), MSH2 in 115 cases (92.7%), MSH6 in 118 cases (95.2%) and PMS2 in 105 cases (84.7%). The majority of absent MMRP cases was detected where the adenoma size was less than 10 mm with LGD (low-grade dysplasia). Survivin expression significantly correlated with the adenoma size and dysplasia grade. Subcellular survivin compartmentalization was statistically associated with the adenoma size, dysplasia grade and adenoma localization. Furthermore, we confirmed a significant relation between survivin expression and MMRP. In general, the intensity of immunoreaction was stronger in the MMRP than in survivin. Conclusions: Our recent results suggest that MMRP may suppress the antiapoptotic activity of survivin in LGD and HGD (high grade dysplasia) colon adenomas. Antecedentes: Las proteínas de reparación de desajustes (MMRP) y survivin representan señales diametralmente opuestas que pueden controlar las vías apoptóticas. Además, se sabe que tanto MMRP como survivin son poderosos parámetros pronósticos. Material y métodos: El objetivo de nuestro estudio fue observar el patrón de expresión inmunohistoquímica de MMRP MLH1, MSH2, MSH6 y PMS2, y survivin en un grupo unificado de 124 adenomatosos pólipos tubulares de colon con respecto a la presencia de anomalías displásicas para explorar sus relaciones. Además, estudiamos su relación con los parámetros clinicomorfológicos, como la edad de los pacientes, el tamaño del adenoma, el grado de cambios displásicos y la localización de la lesión. Resultados: Survivin se expresó en 97 casos (78.2%), MLH1 se encontró en 111 casos (89.5%), MSH2 en 115 casos (92.7%), MSH6 en 118 casos (95.2%) y PMS2 en 105 casos (84.7%). La mayoría de los casos ausentes de MMRP se detectaron en un tamaño de adenoma inferior a 10 mm, estos casos se asociaron principalmente con displasia de bajo grado y fueron más frecuentes en el colon distal. La expresión de survivin se correlacionó significativamente con el tamaño del adenoma y el grado de displasia. La compartimentalización de survivin subcelular se asoció estadísticamente con el tamaño del adenoma, el grado de displasia y localización del adenoma. Además, confirmamos una relación significativa entre la expresión de survivin y el MMRP. En general, la intensidad de la inmunorreacción fue más fuerte en MMRP en comparación con la intensidad del survivin. Conclusiones: Con base en nuestros resultados recientes, sugerimos que el MMRP puede suprimir la actividad antiapoptótica del survivin en los adenomas de colon con displasias de bajo y alto grado.

scholarly journals Evaluation of Epithelial Mesenchymal Transition Markers E-Cadherin and Vimentin in Carcinoma Cervix

2020 ◽  
Vol 7 (6) ◽  
pp. A282-287
Author(s):  
Naveen Kumar R ◽  
Charanjeet Ahluwalia ◽  
Sunita Malik ◽  
Rashmi Arora
Keyword(s):  
Cervical Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Immunohistochemical Expression ◽  
Carcinoma Cervix ◽  
Mesenchymal Transition ◽  
Epithelial Marker ◽  
Risk Of Progression ◽  
Mesenchymal Transformation ◽  
Emt Markers ◽  
E Cadherin

Background: Cervical cancer is the second most common in developing areas. Epithelial to mesenchymal transformation, one of the critical elements in invasion, progression and metastasis of tumour. This study highlights the expression of epithelial mesenchymal markers E-cadherin and vimentin in carcinoma cervix and whether there is any association of expression of these markers with grade of cervical cancer. Objectives: To study the expression of epithelial mesenchymal transition (EMT) markers E-cadherin and vimentin in cervical cancer. To correlate the immunohistochemical expression of these markers with grade of cervical cancer. Methods: 30 cases (n=30) of carcinoma cervix & 30 controls (n=30) of non specific cervicitis diagnosed on H&E were included in this study. H&E stained sections was examined for histological type and grade. Immunohistochemistry for E-Cadherin and Vimentin was performed in all these cases. Result: Immunohistochemical expression of epithelial marker E-cadherin and of mesenchymal marker vimentin was correlated with the grade of cervical carcinoma. The expression of E-cadherin is reduced and expression of vimentin is increased with increasing grades of carcinoma cervix. Conclusion: The expression of these EMT markers can be used as a prognostic marker in cervical cancer that are in high risk of progression.

Immunohistochemical Expression of p53 and Ki67 in Colorectal Adenomas and Prediction of Malignancy and Development of New Polyps

2008 ◽  
Vol 23 (2) ◽  
pp. 89-95 ◽  
Author(s):  
R. Vernillo ◽  
B. Lorenzi ◽  
T. Banducci ◽  
C. Minacci ◽  
C. Vindigni ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Statistical Significance ◽  
Colorectal Adenomas ◽  
Low Grade ◽  
High Grade ◽  
Immunohistochemical Expression ◽  
Ki67 Expression ◽  
P53 Immunoreactivity ◽  
Clinicopathological Variables

The aim of this study was to investigate the immunohistochemical expression of p53 and Ki67 in colorectal adenomas in order to clarify their significance as indicators of malignancy and development of new polyps. Seventy-eight polyps were removed from 51 patients and examined. Twenty-nine patients (56.9%) had adenomas with low-grade atypia (13 of them developed new polyps at 3-year follow-up) and 22 (43.1%) had adenomas with high-grade atypia (6 of them developed new polyps at 3-year follow-up). We tested the association between p53 and Ki67 expression and various clinicopathological variables, and regression analysis was performed to identify the risk factors for malignancy and development of new adenomas. A significant correlation between the grade of atypia and p53 immunoreactivity was observed. Ki67 expression was not related to atypia and no correlation was found between p53 and Ki67 immunoreactivity. Regression analysis showed that size (p=0.0002) and p53 staining (p=0.0111) were the selected factors related to malignant transformation, whereas the number of synchronous primary polyps emerged as the only predictive factor of development of new adenomas, although without statistical significance. The expression of biological markers may be in future added to the currently examined features of polyps; however, further studies are needed to better define their predictive value.

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