Expression of Wnt-1, beta-catenin and c-myc in Ovarian Epithelial Tumor and Its Implication

Objective： To investigate the expression of Wnt-1, beta-catenin and c-myc in normal ovarian epithelial cell and malignant ovarian epithelial tumor. Methods： Immunohistochemical staining with SP method was conducted to identify the expression of Wnt-1, beta-catenin and c-myc in 18 samples of normal epithelial tissue and 34 cases of malignant epithelial tumor of ovary. Results： The expression rate of Wnt-1 and c-myc in malignant epithelial tumors was higher than those in normal epithelial cell （P〈0.05）. The abnormal expression rate of beta-catenin in malignant ovarian epithelial tumors was higher than that in normal epithelial cell （P〈0.05）. A significant positive correlation was found between Wnt-1, beta-catenin and c-myc in malignant ovarian epithelial tumor （P〈0.05）. A significant difference of expressions of Beta-catenin and C-myc was found between serous and mucinous tumors （P〈0.05）. Conclusion： The abnormal expression of Wnt-1, beta-catenin and c-myc might indicate the malignant transformation in ovarian epithelial tumors.     

Expressions of beta-catenin, APC Protein, C-myc and Cyclin D1 in Ovarian Epithelial Tumor and Their Implication

Objective： To investigate the expressions of beta-catenin, protein APC （adenomatous polyposis coil protein）, c-myc and cyclin D1 and their implication in ovarian epithelial tumor. Methods： Immunohistochemical staining with SP method was conducted to identify the expressions of beta-catenin, APC protein, c-myc and cyclin D1 in ovarian epithelial tumor in 48 cases. Results： The abnormal expression rate of beta-catenin in malignant and borderline ovarian epithelial tumors was higher than that in benign epithelial tumors （P〈0.01）. The expression rates of c-myc and cyclin-D1 in ovarian malignant and borderline epithelial tumors were higher than those in benign epithelial tumors too（P〈0.05）. The prevalence of APC protein positive expression in benign epithelial tumors were significantly greater than that in malignant epithelial tumors （P〈0.05）. A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors; while a significant positive correlation was found between beta-catenin, c-myc and cyclin-D1 in ovarian epithelial tumor （P〈0.05）. Conclusion： The abnormal expressions of Beta-catenin, APC protein, c-myc and cyclin-D1 might be used to indicate the malignance transform of ovarian epithelial tumors.     

Anthropometric Measurements and Epithelial Ovarian Cancer Risk in African–American and White women

Previous studies of anthropometric factors and ovarian cancer risk have been inconsistent and none have evaluated the association among African–American women. Data from a population-based, case–control study of 593 cases and 628 controls were used to evaluate ovarian cancer risk in relation to weight, height, body mass index (BMI) and waist-to-hip ratio (WHR). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed and established risk factors were adjusted for using logistic regression models, stratified by race. Among all races, weight at age 18, WHR, weight and BMI one year prior to interview were associated with elevated ovarian cancer risk. When stratified by race, the association between WHR and ovarian was similar among Whites and among African Americans. However, African–American women in the fourth quartile of height had an elevated risk of ovarian cancer (OR = 3.2; 95% CI = 1.3–7.8), but this risk was not apparent in Whites (OR = 1.0; 95% CI␣ = 0.7–1.4). These findings support the hypothesis that obesity is an important risk factor of ovarian cancer among African–Americans and Whites and also suggest that height may be a risk factor specific to African–Americans.^★ This work was performed at the Duke University Comprehensive Cancer, Durham, NC, USA.     

Expression of Vascular Endothelial Growth Factor-C and Vascular Endothelial Growth Factor Receptor-3 in Ovarian Epithelial Tumors

Objective： To explore the role of vascular endothelial growth factor-C （VEGF-C） in the process of angiogenesis, lymphangiogenesis and lymphatic metastasis in epithelial ovarian tumors. Methods： In situ hybridization and immunohistochemical staining for VEGF-C were performed in 30 epithelial ovarian carcinomas, 9 borderline tumors and 26 benign tumors. Endothelial cells were immunostained with anti-VEGFR-3 pAb and anti-CD31 mAb, and VEGFR-3 positive vessels and microvessel density （MVD） were assessed by image analysis. Results： VEGF-C mRNA and protein expression were detected in cytoplasm of carcinoma cells. VEGF-C mRNA and protein expression in ovarian epithelial carcinomas were significantly higher than those in borderline tumors and benign tumors （P〈0.05 or P〈0.01）. In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3 positive vessels and MVD were significantly higher in the cases of clinical stage Ⅲ-Ⅳ and with lymph node metastasis than those of clinical stage Ⅰ-Ⅱ and without lymph node metastasis respectively （P〈0.05 or P〈0.01）. VEGFR-3 positive vessels and MVD were significantly higher in VEGF-C protein positive tumors than negative tumors （P〈0.05）. VEGFR-3 positive vessels was significantly correlated with MVD（P〈0.01）. Conclusion： VEGF-C might play a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in epithelial ovarian tumors, and VBEGF-C could be used as a biologic marker of metastasis in ovarian epithelial tumors.     

Adult Extrarenal Wilms’ Tumor Mimicking Mixed Epithelial and Stromal Tumor in the Retroperitoneum: A Case Report with Immunohistochemical Study and Review of the Literature

We report an extremely rare case of adult extrarenal Wilms’ tumor (WT) in a 52-year-old woman who presented with fever and abdominal distension. Computed tomography revealed a well-defined mass lesion measuring 15.0 cm in the right retroperitoneum and that was in contact with the right kidney. The mass and kidney were surgically removed. Grossly, the mass was well-defined, measuring 16.3 × 11.0 × 9.8 cm, and appearing grayish-white in color. The border between the mass and the kidney was well-defined. Histologically, the tumor showed a triphasic pattern consisting of stromal, epithelial and blastemal components. The stromal component was predominant in the tumor and consisted both of spindle cells and smooth muscle cells. The epithelial component showed a mature glandular structure. Immunohistochemically, the stromal component was positive for vimentin, smooth muscle actin and desmin. The blastemal component was positive for vimentin, while the epithelial component was positive for cytokeratin (CK) 18, CK7 and vimentin. WT-1 was negative in the all three components, and the Ki-67 proliferation index was low. The postoperative histopathological diagnosis indicated extrarenal WT arising in the retroperitoneum. Although not treated by either chemotherapy or radiation therapy, she was free from disease recurrence for 30 months after surgery. To the best of our knowledge, this report is only the fourth case of adult extrarenal WT arising in the retroperitoneum. Furthermore, the present case showed predominant smooth muscle differentiation and a mature glandular structure, mimicking a mixed epithelial and stromal tumor.     

Stromal Expression of CD34, α-Smooth Muscle Actin and CD26/DPPIV in Squamous Cell Carcinoma of the Skin: A Comparative Immunohistochemical Study

Invasion pathogenesis is one of the most complicated issues in the literature. There are numerous studies concerning the tumor markers implicated in the preinvasive-invasive tumor sequence. Despite ample studies on the invasion pathogenesis of cutaneous melanomas, there is limited and dispersed work presently available on non-melanoma skin cancer. The vast knowledge in the literature concerning this issue in squamous cell carcinoma comes mostly from the studies of the oral cavity, esophagus, larynx, and cervix. In this study, we investigated tumor-free neighboring stroma and tumor stroma in squamous cell carcinomas (SCCs) of the skin as well as keratoacanthomas (KAs) with respect to the presence of stromal CD34-positive (CD34+) fibrocytes and α-smooth muscle actin-positive (α-SMA+) myofibroblasts using seborrheic keratosis (SKs) and non-tumoral skin samples as controls. We also evaluated the stromal expression pattern of CD26/DPPIV (CD26), a tumor suppressor gene product that also has immunoregulatory properties. Immunohistochemistry was performed on samples of 31 SCC, 8 KA, 15 SK and 10 non-tumoral skin samples. Peri-tumoral stroma from resection margins was also evaluated. We found that CD34 and α-SMA demonstrated significantly different staining between benign and malignant squamous skin lesions consisting of a loss of CD34+ fibrocytes paralleled by a gain of α-SMA+ myofibroblasts in malignant tumor stroma. Additionally, it was shown that CD26 expression was lower in tumor stroma when compared to that of tumor neighboring stroma. However, we concluded that this finding may be attributable to the solar elastosis areas in the peritumoral tissue, which shows diffuse strong positivity for this marker.     

Expression of Ki-67 and Βeta-Catenin in Pseudoepitheliomatous Hyperplasia and Squamous Cell Carcinoma in Oral Mucosal Biopsies : An Immunohistochemical Study

Objective: To examine the immunohistochemical expression of Ki-67 and beta-catenin in pseudoepitheliomatous hyperplasia and squamous cell carcinoma (SCC) in oral mucosal biopsies. Methods: In this comparative cross sectional study, 70 cases of each PEH and OSCC were taken from the patients of both genders and in all age groups. Study was conducted at Armed Forces Institute of Pathology (AFIP), Rawalpindi from Dec 2017 to March 2019. Statistical analysis was done with the help of SPSS Version 24.0. We used Chi-Squared test with p value of < 0.05 which was considered as statistically significant. Results: In the current study, 80 (57.1%) male and 60 (42.8%) female patients with the mean age of 51.69 ± 16.121 (mean ± SD) years were included. It was found that 6-25% Ki-67 labeling index was observed in all (70) PEH cases, which involved only basal layer of the epithelium. Whereas, Ki-67 labeling index was highly expressed in tumor of high grade malignancy than tumor of low grade malignancy. On the other hand, expression of membranous beta-catenin was higher in PEH and cytoplasmic beta-catenin expression was higher in OSCC. Conclusion : It is concluded that Ki-67 and beta-catenin showed significant expression in PEH and OSCC in oral mucosal biopsies especially those with intense inflammation or unoriented tissue, helping the clinicians to arrive at a final diagnosis before planning any surgical intervention.     

Immunohistochemical Analysis of E-Cadherin,p53 and Inhibin-α Expression in Hydatidiform Mole and Hydropic Abortion

The purpose of this study was to investigate the role of E-cadherin, p53, and inhibin-α immunostaining in the differential diagnosis of hydropic abortion (HA), partial hydatidiform mole (PHM), and complete hydatidiform mole (CHM). E-cadherin, p53, and inhibin-α protein expression patterns were investigated immunohistochemically using paraffin -embedded tissue sections from histologically diagnosed cases of HA (n?=?23), PHM (n?=?24), and CHM (n?=?23). Expression patterns of these markers were scored semi-quantitatively according to the staining intensity, percentage of positive cells, and immunoreactivity score. Classification of cases was established on histologic criteria and supported by the molecular genotyping. Immunostaining allowed the identification of specific cell types with E-cadherin, p53, and inhibin-α expression in all cases. E-cadherin expression was detected on the cell surface of villous cytotrophoblasts. We observed a marked decline in the expression of E-cadherin from HAs to PHMs to CHMs. The p53-positive reaction was restricted to the nucleus of villous cytotrophoblasts. Significantly increased p53 expression was observed in CHMs, compared with HAs and PHMs. The expression of inhibin-α was localised in the cytoplasm of villous syncytiotrophoblasts, and the expression of this marker was significantly higher in PHMs and CHMs than HAs. In conclusion, immunohistochemical analysis of E-cadherin, p53, and inhibin-α expression could serve as a useful adjunct to conventional methods in the differential diagnosis of HA, PHM, and CHM.     

Ki67, CD105, and α-SMA Expression Supports Biological Distinctness of Oral Squamous Cell Carcinoma Arising in the Background of Oral Submucous Fibrosis

Background: The clinicopathological distinctness of oral squamous cell carcinoma arising in the background of oral submucous fibrosis (OSCC-OSF) is well known; however, the molecular distinctness of this unique OSCC-OSF has not been investigated to date. With this in mind, we compared the expression of Ki67, CD105, and α-SMA between OSCC-OSF and oral squamous cell carcinoma (OSCC). Methods: Formalin-fixed paraffin-embedded tissues of 105 OSCC-OSF and 112 OSCC cases were subjected to immunohistochemistry for evaluation of Ki67, CD105, and α-SMA expression. Results: Ki67 (labeling index) LI, MVD and α-SMA expression were significantly higher in OSCC compared to OSCC-OSF. Ki67 LI and MVD was significantly higher in OSCC compared to OSCC-OSF in parameters such as well-differentiated, early TNM stage, non-metastatic, and more than 3-year survival. α-SMA expression was significantly higher in OSCC compared to OSCC-OSF in parameters such as moderate differentiation, metastatic lesions, and survival less than 3 years. Ki67 LI, MVD and α-SMA showed significant positive correlation with each other in OSCC and OSCC-OSF. Conclusion: Proliferation, neoangiogenesis and myofibroblast differentiation were significantly higher in the OSCC group compared to the OSCC-OSF group. This suggests the biological distinctness of OSCC-OSF, which could help the future development of targeted therapies.     

Recurrent Pancreatic Arteritis and Vasculogenic Relapsing Pancreatitis in Rheumatoid Arthritis – A Retrospective Clinicopathologic and Immunohistochemical Study of 161 Autopsy Patients

The aim of this study was to determine: the prevalence, and histological characteristics of vasculitis in the pancreas, and to follow the formal pathogenesis of multifocal pancreatitis due to arteritis and/or arteriolitis (multifocal vasculogenic pancreatitis). A randomized autopsy population of 161 in-patients with rheumatoid arthritis (RA) was studied. Systemic vasculitis (SV) complicated RA in 36 (22.36%) of 161 cases; tissue samples of pancreas were available for histologic evaluation in 28 patients. Pancreatitis and vasculitis were characterized histologically and immunohistochemically. Vasculogenic, multifocal pancreatitis was not recognized clinically. Vasculitis of the pancreatic arterioles and small arteries (branches of splenic artery, upper and lower gastroduodenal arteries) can lead to local ischaemia and to regressive changes in the pancreas. This vasculogenic process is more or less widespread and multifocal, depending on the number of involved vessels and is followed by reactive inflammation, depending on the stages of the pathological process. Because of the recurrent nature of vasculitis with time these regressive changes accumulate within the pancreas and may contribute to an unexpected circulatory failure and sudden death of the patient. Vasculogenic microinfarcts in the pancreas may be clinically characterized by unexplained recurrent abdominal symptoms and spontaneous remissions which insidiously may lead to metabolic failure resistant to therapy.     

Immunohistochemical Study of the Angiogenetic Network of VEGF,HIF1α, VEGFR-2 and Endothelial Nitric Oxide Synthase (eNOS) in Human Breast Cancer

Background  

The role of Nitric Oxide (NO) in angiogenesis has not been fully clarified yet. A dual role for NO, either inductive or inhibitory, has been proposed on the basis of different effects that high or low concentrations of NO may exert on the angiogenic process. Additionally, it has been referred that NO may induce VEGF production, while VEGF may induce NO production via up-regulation of the endothelial nitric oxide synthase (eNOS), the two pathways being reverse. The aim of the current study was to investigate the expression of key molecules involved in these opposite pathways in primary breast cancer.     

Ultrasound Operators’ Confidence Influences Diagnosis of Ovarian Tumors - a Study in China

Aim: To assess the effect of ultrasound operators’ confidence in diagnosis of ovarian cancer, and the factorsinfluencing diagnostic accuracy. Methods: Ultrasound images of selected ovarian cancers and controls wereevaluated by 8 sinologists who were instructed to diagnose and classify lesions into benign, borderline ormalignant, and we use structured questionnaire to investigate the level of confidence. We analyzed the accuracyof diagnosis, including sensitivity, specificity, positive and negative likelihood ratios and accuracy dependingon the different levels of confidence. In addition, factors influencing diagnostic accuracy was assessed bylogistic regression analysis. Results: A total of 426 cases were examined. The confidence score was significantlyincreased with the level of accuracy (test for trend, p<0.05). Borderline tumors were most difficult to diagnose,and had lower accuracy, sensitivity and specificity compared with benign and primary invasive tumors. Workingexperience was positively closely associated with diagnosis accuracy. Logistic regression analysis revealed workingexperience and confidence score to be positively related to the diagnostic accuracy(OR, 95%CI, 1.68, 1.15-3.97for working experience; OR, 95%CI, 3.75, 1.67-6.98 for confidence score). Conclusion: Our study showed thatlevel of confidence is positively associated with diagnostic performance, and the accuracy is greatly influencedby working experience and confidence score.     

Immunohistochemical Detection of Phospho-Akt,Phospho-BAD,HER2 and Oestrogen Receptors α and β in Malaysian Breast Cancer Patients

Activation of Akt signaling pathway has been documented in various human malignancies, including breast carcinoma. The objective of this study is to determine the incidence of Akt phosphorylation in breast tumours and its relationship with expression of ER-α, ER-β, HER2, Ki-67 and phosphorylated Bcl-2 associated death domain (p-BAD). Immunohistochemical staining was performed to detect these molecules on 43 paraffin-embedded breast tumour tissues with commercially available antibodies. Eighteen (41.9%), 3 (7.0%), 23 (53.5%), 35 (81.4%), 21 (48.8%), 29 (67.4%), and 34 (81.0%) of breast tumours were positive for nuclear ER-α, nuclear ER-β, membranous HER2, cytonuclear p-Akt (Thr308), p-Akt (Ser473), p-BAD and Ki-67, respectively. ER-α expression was inversely correlated with HER2 and Ki-67 (P = 0.041 and P = 0.040, respectively). The p-Akt (Ser473) was correlated with increased level of p-BAD (Ser136) (P = 0.012). No relationship of Akt phosphorylation with HER2, ER-α or ER-β was found. The p-Akt (Ser473) immunoreactivity was significantly higher in stage IV than in stage I or II (P = 0.036 or P = 0.009). The higher Ki-67 and lower ER-α expression showed an association with patient age of <50 years (P = 0.004) and with positive nodal status (P = 0.033), respectively. Our data suggest that the Akt phosphorylation and inactivation of its downstream target, BAD may play a role in survival of breast cancer cell. This study does not support the simple model of linear HER2/PI3K/Akt pathway in breast cancer.     

Immunohistochemical analysis of the mutant epidermal growth factor, ΔEGFR,in glioblastoma

The naturally occurring mutated form of the epidermal growth factor receptor, ΔEGFR (also named EGFRvIII and de2-7EGFR), greatly enhances glioblastoma (GBM) cell growth in vivo through several activities, such as down-regulating p27 and up-regulating BclX(L) while increasing signaling through the RAS-MAPK and PI3-K cascades. More than half of GBMs, especially of the de novo type, overexpress EGFR, and 50%–70% of these express ΔEGFR. However, little is known about the distribution of ΔEGFR-expressing tumor cells within surgical specimens. In order to address this clinically important issue, we performed immunohistochemical analyses of 53 GBMs obtained during surgery using the anti-ΔEGFR monoclonal antibody, DH8.3. We also simultaneously analyzed wild-type EGFR expression in these tissues using the anti-EGFR monoclonal antibody, EGFR. 113. ΔEGFR and wild-type EGFR expression were observed in 20/53 (38%) and 29/53 (55%), respectively. Nineteen (95%) of the ΔEGFR-positive tumors also expressed wild-type EGFR; one case was ΔEGFR-positive but wild-type EGFR-negative. In 13/20 (65%) of the ΔEGFR-positive tumors, tumor cells were scattered diffusely within the tumors, 6/20 showed geographical distribution of ΔEGFR-positive tumor cells, and one case showed homogeneous staining. In the wild-type EGFR-positive cases, almost all tumor cells expressed EGFR. The differential distribution of cells expressing the two receptors observed here may suggest either that ΔEGFR arises at a low frequency from wild-type EGFR-expressing cells, perhaps during the process of gene amplification, or that there is a paracrine-type of interaction between them.     

Is There a Survival Benefit of Adjuvant Chemotherapy in Stage IC1 Epithelial Ovarian Cancer Patients? A Meta-Analysis

The purpose of the present systematic review is to clarify whether adjuvant chemotherapy improves survival rates in women with stage IC1 ovarian cancer. We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar. We considered comparative observational studies and randomized trials that investigated survival outcomes (progression-free (PFS) and overall survival (OS)) among women with intraoperative rupture of early-stage epithelial ovarian cancer who received adjuvant chemotherapy and those that did not. Eleven studies, which recruited 7556 patients, were included. The risk of bias was defined as moderate after assessment with the Risk of Bias in non-Randomized Trials tool. Meta-analysis was performed with RStudio. Seven studies investigated the impact of adjuvant chemotherapy on recurrence-free survival of patients experiencing intraoperative cyst rupture for otherwise stage I ovarian cancer. The outcome was not affected by the use of adjuvant chemotherapy as the effect estimate was not significant (HR 1.24, 95% CI 0.74, 2.04). The analysis of data from 5 studies similarly revealed that overall survival rates were comparable among the two groups (HR 0.75, 95% CI 0.54, 1.05). This meta-analysis did not detect any benefit from adjuvant chemotherapy for stage IC ovarian cancer patients with cyst rupture. However, conclusions from this investigation are limited by a study population which included multiple histologic subtypes, high and low grade tumors and incompletely staged patients.     

Immunohistochemical Assessment of E-cadherin and β-catenin in the Histological Differentiations of Oral Squamous Cell Carcinoma

The aim of this study was to establish the expression and localization of E-cadherin and β-catenin inoral squamous cell carcinomas (OSCC) so that we could correlate the findings with prognostic-relevanthistopathological variables. E-cadherin and β-catenin expression in normal oral epithelia and in oral squamouscell carcinomas was examined immunohistochemically, and associations with histopathological differentiationand prognosis were then analyzed in 33 patients who had been operated on for OSCC. E-cadherin expressionwas found in (82%) of the squamous cells of well differentiated OSCC, (61%) of moderately differentiatedand (39%) of poorly differentiated. E-cadherin expression was significantly associated with histological grade(p=0.000). No nuclear staining was detected. In (19.5%) of the cells E-cadherin localized in the cytoplasm, withno correlation to the histological grade (p=0.106). β-Catenin expression was found in 87% of the squamous cellsof well differentiated OSCC, 67% of moderately differentiated and 43% of poorly differentiated, the expressionwas significantly associated with histological grade (p=0.000). the nuclear β-Catenin expression appeared in 3.3%of the cells and it was correlated to the histological grade (p=0.000). In (23.5%) of the cells β-Catenin localizedin the cytoplasm, with correlation to the histological grade (p=0.002). According to this study the expression ofβ-catenin and E-cadherin were independent prognostic factors for histological grade. E-cadherin was closelylinked to β-catenin expression in OSCC (p=0.000) and to tumor differentiation. That reflects a structuralassociation and the role of both in tumor progression.