EpCAM, Ki67, and ESM1 Predict Hepatocellular Carcinoma Recurrence After Liver Transplantation.

Liver transplantation (LT) is a good therapeutic decision, cures hepatocellular carcinoma (HCC) and promotes survival of cases with unrespectable HCC based on the Milan criteria. HCC still recur after LT. Identifying high risk tissue markers that predict recurrence becomes important for LT decision-making. Little is known regarding use of tissue expression of epithelial cell adhesion molecule (EpCAM) to predict HCC recurrence. This study investigates the role of EpCAM, Ki67, and endothelial-cell-specific molecule-1 (ESM1) as immunohistochemical markers to predict HCC recurrence after LT. It included 52 explanted HCC tissues from Egyptian patients who had undergone LT for HCC according to Milan criteria. Immunohistochemical staining was done on paraffin-embedded formalin-fixed tissue sections. HCC recurrence occurred in 13.5% cases. Positive EpCAM expression in HCC, was significantly associated with HCC recurrence, ( P =0.011), achieving 71.43% sensitivity, 84.44% specificity and 78.8% accuracy in predicting recurrence. High Ki67 percentage was significantly associated with HCC recurrence, ( P =0.005), achieving 57.14% sensitivity, 86.67% specificity and 82.69% accuracy in predicting HCC recurrence. ESM1 showed significant association with HCC recurrence ( P =0.041), with 71.43% sensitivity, 71.11% specificity and 71.15% accuracy in predicting HCC recurrence. EpCAM score and Ki67 percentage showed positive correlation. In conclusion, it is suggested that large tumor size (≥3 cm), advanced pathologic staging and Ki67 could be stratified as high risk predictors of HCC recurrence after LT. Although higher classes of Child-Turcotte-Pugh classification, high serum alpha-fetoprotein, microvascular invasion, positive EpCAM and ESM1 are stratified as lower risk predictors of HCC recurrence after LT.

Role of SET oncoprotein in hepatocellular carcinoma: An immunohistochemical study.

Hepatocellular carcinoma (HCC) is the most prevalent primary cancer of the liver and it is the fourth most common cause of cancer related death worldwide. In Egypt, liver cancer constitutes the most common cause of mortality-related cancer. This study aimed to evaluate the immunohistochemical expression of SET oncoprotein in HCC tissues in comparison with its expression in non tumorous liver tissues and to correlate its expression with clinicopathological parameters. This study investigated 100 cases of HCC (including tumorous and non tumorous tissues). One hundred percent of tumorous and non-tumorous tissues were positive for SET expression. The mean and median values of H-score for SET expression were higher in tumorous than non tumorous tissues (P = .03). Higher SET expression was significantly correlated with larger tumor size (P = .012), positive lymphovascular invasion (P = .028), and shorter overall survival (P < .001). SET expression in tumor tissues is the most independent factor to affect the overall survival of HCC patients. SET plays a role in hepatocarcinogenesis proved by the increase of SET expression from non-tumorous to tumorous tissues. Also, SET can be used as a prognostic indicator and a novel target therapy in HCC patients.

Adequacy criteria of Tru-cut needle liver biopsy in neonatal cholestasis.

INTRODUCTION AND OBJECTIVES: Assessment of liver biopsy sample adequacy criteria is essential to avoid sampling errors in patients with diffuse liver pathology. Many studies have evaluated these criteria in adults; however, no previous studies have been performed on neonatal liver disorders. We aimed to assess the adequacy criteria of Tru-cut needle liver biopsy samples in infants with neonatal cholestasis (NC). METHODS: In a retrospective analysis of infants who underwent liver biopsy for NC within a one-year duration, 58 specimens were recruited. The core lengths after fixation were measured. All samples were acquired with a 16-gauge (G) Tru-cut needle. Serial shortening of these samples was performed to define the smallest core length that gives representative parenchyma that could determine the activity grade and fibrosis stage reported by larger cores. RESULTS: It was found that a 4-mm core length with a complete portal tract (CPT) number of 8±3 could adequately assess the NC activity grade. In addition, a 6-mm core length with a CPT number of 11±3 could adequately estimate NC fibrosis stage. CONCLUSIONS: The adequacy criteria of liver tissue samples for the accurate assessment of NC are different from those defined for adult diffuse liver pathology. At least a 4-mm core length with a CPT number of 8±3 and a 6-mm core length with a CPT number of 11±3 acquired by a 16-G Tru-cut needle should be used to assess NC activity grade and fibrosis stage, respectively.

Clinico-pathological assessment of surgically removed abdominal wall endometriomas following cesarean section.

BACKGROUND: Over the past few decades, the rate of Cesarean Section (CS) delivery has been rising rapidly and the prevalence of CS-associated complications including Abdominal Wall Endometriomas (AWE) increases with each additional operation. The aim of this study was to evaluate the clinical characteristics, histopathological diagnostic role and surgical management of post-CS AWE through a retrospective case review. METHODS: We calculated the incidence of AWE and reviewed all the patients underwent surgical removal of Post-CS AWE during the period of 2012-2018 who were diagnosed, treated and followed up for 2-8 years at our tertiary hospital. RESULTS: Thirty women with AWE were included. The main symptom in 2/3 of cases was cyclic pain and 4 cases (13.3%) had no symptoms. The mean interval between prior CS and appearance of symptoms was 55.2 months and the mean size of the excised mass was 42 mm. Free surgical margin was less than 9 mm in 9 patients (30%) but no recurrence was recorded among all the studied patients. Pre-operative FNAC diagnosis was performed for only 3 patients (10%) which helped in excluding other potential pathologies. The clinical-pathological agreement value for detection of the nature of the abdominal wall mass was 93.4%. CONCLUSIONS: Patients with suspected AWE should undergo preoperative cytological biopsy to exclude alternative diagnosis. Wide surgical excision with margin of less than 1 cm could be accepted especially in case of weak abdominal wall. More studies on the post-CS complications; risks, prevention, early detection and proper management should be encouraged.

SOX9 in biliary atresia: New insight for fibrosis progression.

BACKGROUND: Liver fibrosis is a hallmark determinant of morbidity in biliary atresia (BA) even in successfully operated cases. Responsible factors for this rapid progression of fibrosis are not completely defined. Aberrant expression of the transcription factor SOX9 and hepatic progenitor cells (HPCs) proliferation have roles in fibrogenesis in cholestatic disorders. However, they were not investigated sufficiently in BA. We aimed to delineate the relation of SOX9 and HPCs to fibrosis and its progression in BA. METHODS: Forty-eight patients with BA who underwent an initial diagnostic liver biopsy (LB) and consequent intraoperative LB were recruited and compared to 28 cases with non-BA cholestasis that had an LB in their diagnostic workup. Liver fibrosis, tissue SOX9 and HPC expressions were studied in both BA and non-BA-cholestasis cases. Liver fibrosis, SOX9, and HPCs' dynamic changes in BA cases were assessed. Relation of fibrosis and its progression to SOX9 and HPCs in BA was assessed. RESULTS: SOX9 and HPCs in ductular reaction (DR) form were expressed in 100% of BA and their grades increased significantly in the second biopsy. The rapidly progressive fibrosis in BA, represented by fibrosis grade of the intraoperative LB, correlated significantly to SOX9-DR and HPC-DR at the diagnostic (r = 0.420, P = 0.003 and r = 0.405, P = 0.004, respectively) and the intraoperative (r = 0.460, P = 0.001 and r = 0.467, P = 0.001, respectively) biopsy. On the other hand, fibrosis, SOX9-DR, and HPC-DR were significantly lower in non-BA cases at a comparable age (P < 0.001, P = 0.006, and P = 0.014, respectively). CONCLUSIONS: Fibrosis in BA is rapidly progressive within a short time and is significantly correlated to SOX9 and HPCs. Assessment of targeting SOX9 and HPCs on fibrosis progression is warranted.

Temporal histopathological changes in biliary atresia: A perspective for rapid fibrosis progression.

INTRODUCTION AND OBJECTIVES: Biliary atresia (BA) is characterized by rapid progression of fibrosis with no definite causes. Histopathological findings have been extensively described, but very few studies have assessed temporal changes in BA. Understanding these short-term changes and their relationship with fibrosis progression could have an impact on ameliorating rapid fibrogenesis. We aimed to study the relationship between temporal histopathological changes and fibrosis progression in BA within a short time interval. PATIENTS AND METHODS: Forty-nine infants with BA who underwent Kasai portoenterostomy, a diagnostic liver biopsy, and an intraoperative liver biopsy were recruited. Histopathological characteristics of the two biopsies were examined. Temporal histopathological changes were assessed by comparing the two types of biopsies. Correlation of temporal changes in fibrosis with age, interval between biopsies, laboratory profiles, and temporal histopathological changes were studied. RESULTS: In the univariate analysis, bile ductular proliferation (BDP), portal infiltrate, giant cells, hepatocellular swelling, and fibrosis showed significant temporal changes within a short interval (5-31 days). BDP and fibrosis showed the most frequent increase in their grades (32/49 and 31/49 cases, respectively). In the multivariate analysis, BDP was the only independent pathological feature showing a significant temporal increase (p = 0.021, 95% confidence interval: 1.249-16.017). Fibrosis progression was correlated with temporal changes in BDP (r = 0.456, p = 0.001), but not with age (p = 0.283) or the interval between the biopsies (p = 0.309). CONCLUSIONS: Fibrosis in BA progresses rapidly and is significantly correlated with BDP. Assessment of targeting BDP as an adjuvant medical therapy is recommended.

Relation Between Immunohistochemical Expression of Hippo Pathway Effectors and Chronic Hepatitis Induced Fibrosis in Egyptian Patients.

OBJECTIVE: Chronic hepatitis is a global health problem especially in Egypt. Hepatic fibrosis is a common end clinical manifestation of many chronic liver diseases. Although it is a wound-healing process, excessive accumulation of fibrillary collagen leads to architectural damage, cirrhosis and liver failure. Recently, a few studies have linked Hippo pathway effectors of yes-associated protein (YAP) and its paralog transcriptional coactivator with PDZ-binding motif (TAZ) to extracellular matrix deposition and ongoing fibrosis. MATERIAL AND METHOD: Immunohistochemical expression of YAP and TAZ were analyzed in 121 liver needle core biopsies (91 core biopsies of chronic viral hepatitis, 20 biopsies of autoimmune hepatitis and 10 normal liver cores). RESULTS: YAP and TAZ nuclear localization was absent in all normal liver cores. Autoimmune hepatitis cases showed higher nuclear expression of both YAP and TAZ in comparison to chronic viral cases. YAP and TAZ expression were correlated with severity of hepatocyte injury together with fibrosis in chronic viral cases but these correlations were absent in AIH cases despite the pronounced increase of YAP and TAZ nuclear localization. CONCLUSION: The correlation between Hippo effectors activation and fibrosis in chronic viral hepatitis patients emphasize their role in the development and advancement of hepatic scarring and highlight the use of both YAP and TAZ as novel targets to ameliorate liver fibrosis.

Hepatoprotective effect of artichoke leaf extracts in comparison with silymarin on acetaminophen-induced hepatotoxicity in mice.

Acetaminophen is a common analgesic-antipyretic agent, which is safe in therapeutic doses but in higher doses can produce hepatic necrosis. The aim of this study is to investigate the hepatoprotective effects of artichoke, silymarin, and both agents in acetaminophen-induced liver damage in mice. Forty male mice were divided into five main groups, (1) control (2) Acetaminophen (APAP) (3) Artichoke leaf extracts (ALE) and APAP (4) silymarin and APAP group (5) ALE, silymarin and APAP groups. Blood samples were collected for the measurement of liver enzymes (ALT, AST, and ALP). The liver was excised, weighed and dissected into two parts, one used for measurement of malondialdehyde (MDA) and glutathione reductase, and the other part used for histopathological examination and assessment of proliferative cell nuclear antigen (PCNA) immunohistochemical expression. APAP group showed a significant increase in liver weight, ALT, AST, ALP, MDA, and PCNA expression with a significant decrease in glutathione reductase in comparison to control group. All these parameters were significantly improved in the three treated groups when compared to APAP group. APAP group showed marked portal inflammation and parenchyma necrosis. Co-administration of ALE and/or silymarin to acetaminophen treated mice showed a significant reduction in PCNA expression compared to APAP group. Both ALE and silymarin co-treatment showed a significant decrease in PCNA percentage to a level near to control group. Artichoke and/or silymarin are suggested to protect against acetaminophen-induced hepatotoxicity in mice by ameliorating liver enzymes, antioxidant effect, decreasing liver damage and proliferation.Abbreviation: ALT, alanine transaminase. AST, aspartate transaminase. ALP, alkaline phosphatase.MDA, malondialdehyde. PCNA, proliferative cell nuclear antigen.

Evaluation of the diagnostic value of emerin and CD56 in papillary thyroid carcinoma - an immunohistochemical study.

Papillary thyroid carcinoma (PTC) is diagnosed in both cytological and histological specimens on the basis of distinct nuclear morphology. These features may not be prominent in some PTC variants and may be seen in some benign conditions. It is necessary to differentiate PTC from other neoplastic and nonneoplastic lesions since it affects treatment strategy and patients' fate. Emerin is a type II integral membrane protein of the inner nuclear membrane that has a characteristic staining pattern in PTC. CD56 is a homophilic membrane glycoprotein that is expressed in thyroid follicular epithelial cells and adrenal glands. The aim of this study was to evaluate the diagnostic value of emerin (positivity, percentage, and highlighting nuclear features) and CD56 (positive versus negative) both singly and in combination for differentiation of PTC from other neoplastic and nonneoplastic mimics. This study was performed on 50 cases of PTC, 9 cases of follicular adenoma (FA), and 12 cases of nonneoplastic thyroid lesions using immunohistochemistry for detection of emerin and CD56. Positive emerin expression was seen in 82% of PTC and in 16.7% of nonneoplastic cases with an absence of expression in FA. CD56 was expressed in 88.9% of FA, 91.7% of nonneoplastic cases and in a minority of PTC cases (6%). Positive emerin revealed 82% sensitivity and 90% specificity, while emerin-highlighted nuclear changes was more specific (95%). Negative CD56 expression revealed 84% sensitivity and 90% specificity. Combined positive emerin (including highlighting nuclear changes) and negative CD56 showed 72% sensitivity and 100% specificity. Positive emerin expression (moderate/strong) and its highlighting nuclear changes combined with negative CD56 could be a very helpful procedure in difficult and overlapping cases with high diagnostic validity (high specificity and positive predictive value).

Immunohistochemical expression HIF1α in chronic plaque psoriasis, an association with angiogenesis and proliferation.

Psoriasis is characterized by excessive cell proliferation, angiogenesis, and regions of hypoxia. Hypoxia stimulates production of hypoxia inducible factors (HIFs) such as HIF1α. The aim of the present study is to investigate the possible role of HIF1α in pathogenesis of psoriasis and to correlate its expression with angiogenesis and proliferation in involved and uninvolved skin in patients with plaque psoriasis using CD34 and Ki-67. The current study was performed on 40 skin specimens of patients presented with chronic plaque psoriasis both involved and uninvolved together with 40 specimens from age- and sex-matched healthy volunteers as a control group. The specimens were submitted for HIF1α, CD34, and Ki-67 immunostaining. HIF1α was expressed in 37.5% of normal skin with mild intensity and cytoplasmic localization instead of its expression in 72.5% and 100% of uninvolved and involved psoriatic skin, respectively. Nucleocytoplasmic pattern of HIF1α was seen in 34.5% and 37.5% of uninvolved and involved psoriatic skin, respectively. Positive and intense expression of HIF1α as well as its nucleocytoplasmic localization were significantly in favor of psoriatic skin either involved or uninvolved in comparison to normal skin (P < 0.05). Intense HIF1α was significantly associated with microvessel density in both involved and uninvolved skin (P < 0.05). Nucleocytoplasmic pattern was significantly associated with epidermal acanthosis (P < 0.05) and tended to be associated with percentage of Ki-67 of psoriatic skin (P = 0.06). The present study demonstrated that HIF1α is upregulated in the skin of psoriatic cases (involved and uninvolved) compared to normal skin indicating its role in pathogenesis of psoriasis especially its active nuclear form that showed an association with angiogenesis and proliferation.