STIM1/SOX2 proteins are co-expressed in the tumor and microenvironmental stromal cells of pancreatic ductal adenocarcinoma and ampullary carcinoma.

Pancreatic ductal adenocarcinoma (PDAC) and ampullary carcinoma (AAC) are lethal malignancies with modest benefits from surgery. SOX2 and STIM1 have been linked to anticancer activity in several human malignancies. This study included 94 tumor cases: 48 primary PDAC, 25 metastatic PDAC, and 21 primary AAC with corresponding non-tumor tissue. All cases were immunohistochemically stained for STIM1 and SOX2 and results were correlated with clinicopathologic data, patient survival, and BCL2 immunostaining results. Results revealed that STIM1 and SOX2 epithelial/stromal expressions were significantly higher in PDAC and AAC in comparison to the control groups. STIM1 and SOX2 expressions were positively correlated in the primary and metastatic PDAC (P = 0.016 and, P = 0.001, respectively). However, their expressions were not significantly associated with BCL2 expression. SOX2 epithelial/stromal expressions were positively correlated with the large tumor size in the primary AAC group (P = 0.052, P = 0.044, respectively). STIM1 stromal and SOX2 epithelial over-expressions had a bad prognostic impact on the overall survival of AAC (P = 0.002 and P = 0.001, respectively). Therefore, STIM1 and SOX2 co-expression in tumor cells and intra-tumoral stroma could contribute to the development of PDAC and AAC. STIM1/SOX2 expression is linked to a bad prognosis in AAC.

Appraisal of Chitosan-Coated Lipid Nano-Combination with Miltefosine and Albendazole in the Treatment of Murine Trichinellosis: Experimental Study with Evaluation of Immunological and Immunohistochemical Parameters.

PURPOSE: Resistance and adverse consequences of albendazole (ABZ) in treating trichinellosis urged demand for secure and effective new drugs. The current study aimed to assess the effect of chitosan-coated lipid nano-combination with albendazole and miltefosine (MFS) in treating experimental murine trichinellosis and evaluating pathological and immunological changes of trichinellosis. MATERIALS AND METHODS: One hundred twenty Swiss albino mice were divided into six groups. Each group was subdivided into a and b subgroups based on the scarification time, which was 7- and 40-days post-infection (PI), respectively. The treatment efficacy was evaluated using parasitological, histopathological, serological (interleukin (IL)-12 and IL-4 serum levels), immunohistochemical (GATA3, glutathione peroxidase1 (GPX1) and caspase-3), and scanning electron microscopy (SEM) methods. RESULTS: The most effective drug was nanostructured lipid carriers (NLCs) loaded with ABZ (G5), which showed the most significant reduction in adults and larval count (100% and 92.39%, respectively). The greatest amelioration in histopathological changes was reported in G4 treated with MFS. GATA3 and caspase-3 were significantly reduced in all treated groups. GPX1 was significantly increased in G6 treated with MFS + NLCs. The highest degenerative effects on adults and larvae by SEM were documented in G6. CONCLUSION: Loading ABZ or MFS on chitosan-coated NLCs enhanced their efficacy against trichinellosis. Although ABZ was better than MFS, their combination should be considered as MFS caused a significant reduction in the intensity of infection. Furthermore, MFS showed anti-inflammatory (↓GATA3) and antiapoptotic effects (↓caspase-3), especially in the muscular phase. Also, when loaded with NLCS, it showed an antioxidant effect (↑GPX1).

Does the expression of granzyme B participate in inflammation, fibrosis, and fertility of hydatid cysts?

Echinococcus granulosus (sensu lato), a cestode that is endemic in Egypt, causes cystic echinococcosis (CE), a significant but neglected zoonotic disease that is prevalent throughout the world. Infected hydatid cysts are classified as fertile or non-fertile based on the presence of protoscoleces; nevertheless, the mechanism of non-fertile CE cysts remains unknown. The study aimed to assess whether granzyme B (GrB) expression and CD4 + /CD8 + could be related to the induction of non-fertile CE cysts. A total of fifty-eight individuals diagnosed with visceral hydatid cysts were selected, and they were further divided according to cyst fertility into fertile and non-fertile. Immunohistochemistry for CD4, CD8, and GrB was done. According to the results, hydatid cysts are common in adults and have no gender preference. The same clinical and laboratory data were shared by patients with fertile and non-fertile cysts (p = 0.186). GrB expression was not impacted by the fibrous deposition inside the hydatid cyst wall (p = 0.85); however, GrB was significantly correlated with the inflammatory density (p = 0.005). GrB expression was also found to be significantly higher in non-fertile cysts (p = 0.04). GrB expression is positively correlated with CD4 and CD8 expression. In conclusion, the expression of GrB in hydatid cysts may exacerbate the inflammatory response and impede cyst fertility while not affecting the fibrous deposition in the cyst wall.

Farnesoid X receptor in chronic liver diseases: an immunohistochemical study.

Chronic hepatitis C virus (HCV) related liver diseases are still an ongoing cause of hepatic failure despite the effective role of direct-acting anti-viral agents. Farnesoid X receptor (FXR) agonists have a potential therapeutic effect on the management of chronic liver diseases (CLD). However, data regarding FXR protein expression in human CLDs are limited and conflicting. We aimed to assess the immunohistochemical expression of FXR in HCV-related chronic hepatitis and cirrhosis in comparison with metabolic-associated fatty liver disease (MAFLD) and normal liver tissue. The expression of FXR was low both in hepatocytes and bile ducts of HCV-related chronic hepatitis and cirrhosis (p = .001, respectively). In addition, a significantly low expression of FXR was observed in HCV-related hepatitis and cirrhosis groups compared to MAFLD in hepatocytes (p < .001, for both) and bile ducts (p = .004 and p = .018). FXR expression in HCV-related cirrhosis was significantly associated with compensated liver function (p = .032) and low inflammatory activity (p = .022). FXR expression decreases in HCV-related CLDs. There was some evidence that FXR expression could protect against post-hepatitis cirrhosis.

Recombinant Mouse Prolactin Confers Partial Protection Against Toxoplasma gondii Infection in a Pre-treated Experimental Murine Model.

INTRODUCTION: Toxoplasmosis is one of the most important health-threatening diseases with worldwide distribution and global impact. It is caused by Toxoplasma gondii (T. gondii), an intracellular apicomplexan parasite that can evade the host immune responses and establish a chronic infection. The available treatments are not efficient against this stage and have many adverse effects. There are no available effective vaccines, apart from Toxovax®, which is used in sheep to prevent abortion. Studies documented that prolactin (PRL) had in vivo and in vitro anti-Toxoplasma effects. Detailed research was recommended about the mechanisms of such inhibitory effects. AIM: This study was designed to assess the possible protective role of the recombinant prolactin (rPRL) against T. gondii. MATERIALS AND METHODS: Sixty experimentally infected mice with T. gondii were used. The treated mice received rPRL for five days before infection. Serum prolactin levels were measured; survival rate was monitored; number, size, and DNA of T. gondii cysts in the brain were measured; and histopathological and immunological studies were done. RESULTS: There was a significant increase in the survival rate of the rPRL-treated mice, a significant decrease in the number, size, and DNA amount of T. gondii cysts in the brain with a noticeable improvement of histopathological lesions in the brain and liver tissues when compared to the infected untreated group. These effects seem to be achieved through stimulating humoral and cell-mediated immune responses that were evident by the significant rise in serum levels of anti-Toxoplasma IgM, IFN-γ, and TNF-α. CONCLUSION: The rPRL elicited robust immune responses, which provided efficient protection against murine T. gondii infection.

Lymphoepithelioma-like Hepatocellular Carcinoma: a Case Report and Review of Literature.

We report a case of hepatic lymphoepithelioma-like carcinoma-hepatocellular carcinoma subtype (LEL-HCC) in a 41-year-old man with chronic hepatitis C virus (HCV) infection. The patient presented with abdominal pain and further assessment revealed a hypoechoic mass on ultrasonography. Serum alpha-fetoprotein (AFP) was 13·6 ng/dl. The patient was diagnosed as hepatocellular carcinoma based on the established triphasic computed tomography (TCT) diagnostic criteria and he underwent a surgical resection of the mass. Microscopic examination showed sheets and cords of malignant epithelial cells intermixed with heavy lymphoid infiltrate, with more than 100 tumor-infiltrating lymphocytes (TILs) per 10 high-power-field (HPF). Based on immunohistochemical studies, the malignant cells were positive for Hep Par 1 and glypican 3, focally positive for cytokeratin 7 (CK7), and negative for cytokeratin 20 (CK20). TILs were diffusely positive for cluster of differentiation 3 CD3 with an approximately equal CD4/CD8 ratio. The patient was recurrence free at 25 months after surgery, as evident by CT and serum alpha-fetoprotein level. LEL-HCC is a rare variant of HCC with a relatively better prognosis. Exploring the potential for immune modulator-based therapy in this subset of tumors is highly recommended.

Role of liver biopsy in management of liver diseases without hepatic nodules following end of the interferon era: experience of a tertiary referral center.

Liver biopsy (LB) is the cornerstone in the management of patients with liver diseases. However, a lot of queries had emerged about its role following the end of the interferon era. The aim of this study was to re-evaluate the current role of LB in the diagnosis of liver diseases. All patients who had underwent LB at the Department of Hepatology, National Liver Institute, from January 2015 through December 2018 were recruited. Indications for LB, pathology reports and medical records of all cases were retrieved, reviewed and statistically analyzed. A total of 275 liver biopsies were collected, 191 males and 84 females with mean age 41.22 ± 13.36 years. Etiological diagnosis made by histopathological evaluation was 48 drug-induced liver injury (DILI), 42 nonalcoholic fatty liver disease (NAFLD), 34 chronic hepatitis B, or C with cholestasis, 29 autoimmune hepatitis, 34 primary sclerosing cholangitis, 13 primary biliary cholangitis, 7 autoimmune overlap syndrome, 13 active bilharziasis and 10 Wilson's disease. Minor number of cases was diagnosed by different other etiologies. Initial diagnosis was made by liver biopsy and confirmed by clinical response and laboratory findings. Liver biopsy is still considered as the gold standard diagnostic measure of different liver diseases representing an integral component of management decisions in hepatology.

The expression of VEGF and cyclin D1/EGFR in common primary liver carcinomas in Egypt: an immunohistochemical study.

Background: The most common types of primary malignant liver tumours are hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Treatment options for patients who are inoperable/advanced, or recurring are challenging. Cyclin D1, epidermal growth factor (EGFR) and vascular endothelial growth factor (VEGR) are common carcinogenic proteins that have potential therapeutic targets in various cancers. They have been implicated in the development of HCC and CCA. In this study, we aimed to evaluate the oncogenic function expression of cyclin D1, EGFR and VEGF in HCC and CCA of Egyptian patients. This could help to validate their therapeutic potential. Material and methods: Tumour cases were selected from 82 cases of primary liver carcinomas, with 58 cases being from HCC and 24 cases from CCA compared to 51 non-tumour adjacent liver cases and 18 from normal liver tissue. The immunohistochemical study of cyclin D1, EGFR and VEGR was conducted. Results: Cyclin D1, EGFR and VEGF are overexpressed in HCC and CCA as compared to the control group (p < 0.001). Cyclin D1 was related to well-differentiated grade and early pathologic stage in HCC (p = 0.016 and p = 0.042, respectively). The well-differentiated grade showed significantly higher VEGF levels (p = 0.04). In the CCA group, however, EGFR was strongly related to high tumour size (p = 0.047). EGFR and VEGF were overexpressed in HCC raised in the non-cirrhotic liver compared to those developed in post-hepatitic liver cirrhosis (p = 0.003 and p = 0.014). Conclusion: Cyclin D1, EGFR and VEGF shared significant overexpression in HCC and CCA. EGFR and VEGF may play an oncogenic function in the development of HCC in non-cirrhotic liver. Furthermore, cyclin D1 and VEGF may play a good prognostic function in HCC, but EGFR may play a bad prognostic role in CCA.

The clinicopathological and prognostic factors of hepatocellular carcinoma: a 10-year tertiary center experience in Egypt.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a major health problem despite the emergence of several preventive and therapeutic modalities. HCC has heterogeneous and wide morpho-molecular patterns, resulting in unique clinical and prognostic criteria. Therefore, we aimed to study the clinical and pathological criteria of HCC to update the morpho-molecular classifications and provide a guide to the diagnosis of this disease. METHODS: Five hundred thirty pathologically analyzed HCC cases were included in this study. The clinical and survival data of these cases were collected. RESULTS: Hepatitis C virus is still the dominant cause of HCC in Egypt. Post-direct-acting antiviral agent HCC showed an aggressive course compared to interferon-related HCC. Old age, male gender, elevated alpha-fetoprotein level, tumor size, and background liver were important prognostic parameters. Special HCC variants have characteristic clinical, laboratory, radiological, prognostic, and survival data. Tumor-infiltrating lymphocytes rather than neutrophil-rich HCC have an excellent prognosis. CONCLUSIONS: HCC is a heterogenous tumor with diverse clinical, pathological, and prognostic parameters. Incorporating the clinicopathological profile per specific subtype is essential in the treatment decision of patients with HCC. TRIAL REGISTRATION: This was a retrospective study that included 530 HCC cases eligible for analysis. The cases were obtained from the archives of the Pathology Department, during the period between January 2010 and December 2019. Clinical and survival data were collected from the patients' medical records after approval by the institutional review board (IRB No. 246/2021) of Liver National Institute, Menoufia University. The research followed the guidelines outlined in the Declaration of Helsinki and registered on ClinicalTrials.gov (NCT05047146).

Expression of cyclo-oxygenase-2 and yap/taz in hepatocellular carcinoma in untreated and treated hepatitis C virus patients.

The pathogenesis of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) differs according to whether prior treatment with interferon (IFN) vs. direct-acting antiviral agents (DAAs) was administered. Cyclo- oxygenase-2 (COX-2), yes-associated protein 1 (YAP), and transcriptional co-activator with PDZ-binding motif (TAZ) play a crucial role in hepatocarcinogenesis. However, their roles in untreated or treated HCV-related HCC development have not been clarified. Therefore, we performed an immunohistochemical study and stained tissue from 83 HCV-related HCC cases using antibodies against COX-2, YAP, and TAZ and correlated their expression with the clinicopathological characteri stics and survival data. The cases were subdivided into 3 groups based on prior HCV treatment. In the 3 groups, COX-2 was significantly higher in HCC tissue compared with adjacent non-tumour liver tissue. However, the expression of YAP/TAZ was not significantly different between HCC and adjacent non-tumour tissue. We further grouped HCC cases into YAP+/TAZ+ and YAP-/TAZ- cases. In the YAP+/TAZ+ cases, COX-2 was significantly associated with tumour size, tumour multifocality, and late pathologic stage. No significant difference was observed in COX-2 and TAZ expression as a result of IFN or DAA treatment; however, YAP was significantly higher in IFN-treated HCC. Cyclo-oxygenase-2 overexpression may play a role in late HCC development, while YAP/TAZ could play an early role in HCC progression. Sustained expression of combined YAP/TAZ could mediate the poor prognostic role of COX-2.

The Prognostic Role of CD73/A2AR Expression and Tumor Immune Response in Periampullary Carcinoma Subtypes.

INTRODUCTION: Periampullary adenocarcinoma (PAAC) is a rare, lethal heterogeneous group of malignancy that differs in their molecular phenotypes. Ecto-5'-nucleotidase (CD73)/adenosine A2A Receptor (A2AR) pathway has shown an emerging role in cancer therapy through modulating the immune response. Therefore, this study aimed to explore the functional role of CD73 and A2AR in pancreatic ductal adenocarcinoma (PDAC) and ampullary carcinoma (AC). MATERIAL AND METHODS: An immunohistochemical study for CD73 and A2AR carried on 48 PDAC cases, 21 AC cases and 34 adjacent non-tumor tissues that were taken from the farthest point of normal pancreatic tissue away from the tumor. RESULTS: CD73 was overexpressed in the PDAC (p < 0.001), and AC (p = 0.004) groups compared to their non-tumor tissues. However, A2AR was overexpressed in the PDAC group (p = 0.003) but not in the AC group (p = 0.359) compared to non-tumor tissue. In the PDAC group, CD73 overexpression was significantly associated with longer overall survival (p = 0.018). In contrary, A2AR overexpression was significantly associated with high grade (p = 0.001) and late- stage (p = 0.01). Both markers had no prognostic impact on AC. In the meantime, tumor immune response showed a negative prognostic role in PDAC and AC. The prognostic role of tumor immune response in the PDAC group was strongly modulated by CD73 and A2AR expression. CONCLUSIONS: PDAC and AC shared CD73 Overexpression while A2AR was overexpressed in PDAC only. In PDAC, CD73 and A2AR showed an opposed  prognostic effect but both had no prognostic impact on AC. In addition, tumor immune response showed a controversial impact on the prognosis of PDAC and AC.

The Potential Utility of Circulating Oncofetal H19 Derived miR-675 Expression versus Tissue lncRNA-H19 Expression in Diagnosis and Prognosis of HCC in Egyptian Patients.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Interestingly, lncRNA-H19 acts independently in HCC and influences miR-675 expressions. We aimed to assess the potential utility of tissue lncRNA-H19 versus miR-675 expressions as a non-invasive biomarker for HCC diagnosis and prognosis in Egyptian patients. Ninety-one HCC patients and 91 controls included in this study were investigated for expression of lncRNA-H19 and miR675 using RT-qPCR. Our results showed that the expression of lncRNA-H19 and microRNA-675 were higher in patients than in controls (p < 0.001 for both). Additionally, lncRNA-H19 expression was higher in tumorous than in non-tumorous tissue (p < 0.001). Linear regression revealed that miR-675 expression was a significantly higher positive predictor than lncRNA-H19 for tumor size, pathologic grade, and AFP level; similarly, for cyclin D1 and VEGF protein expression. By using the ROC curve, the sensitivity of miR-675 was higher than lncRNA-H19 for discriminating HCC from controls (95-89%, respectively) and the sensitivity of lncRNA-H19 was higher in tumorous than in non-tumorous tissues (76%). The high expressions of both were associated with low OS (p < 0.001, 0.001, respectively). Oncofetal H19-derived miR-675 expression could be considered a potential noninvasive diagnostic and prognostic biomarker, outstanding the performance of the expression of tissue lncRNA-H19 for HCC.

Trichrome-positive intrahepatic cytoplasmic globules are potential histopathological clue for COVID-19-induced hepatitis: a case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection mainly affects respiratory system. Later, liver affection has also been reported in the form of marked elevated liver enzymes. However, the association of coronavirus disease-19 (COVID-19) and autoimmune diseases is not clear. CASE PRESENTATION: A female patient with a known history of autoimmune hemolytic anemia (AIHH) for which she was treated with prednisolone was admitted for uncontrolled anemia followed by fever and elevated liver enzymes. All the laboratory and radiological investigations were not typical for COVID-19 or any other etiology. Liver biopsy revealed numerous pale eosinophilic trichrome-positive intracytoplasmic globules. The pathology raised the suspicion for SARS-CoV-2-associated hepatitis, which was confirmed by a positive IgG titer. The patient showed a dramatic improvement on the maintenance dose of prednisolone. CONCLUSIONS: AIHA patients co-infected with SARS-CoV-2 may be at risk of uncontrolled disease and should continue their treatment regimen. Histopathology has a role in the diagnosis of liver affection due to SARS-CoV-2 infection.

SARS-CoV-2-associated gastrointestinal and liver diseases: what is known and what is needed to explore.

BACKGROUND: The pandemic of COVID19 which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first described in China as an unexplained pneumonia transmitted by respiratory droplets. Gastrointestinal (GI) and liver injury associated with SARS-CoV-2 infection were reported as an early or sole disease manifestation, mainly outside China. The exact mechanism and incidence of GI and liver involvement are not well elucidated. MAIN BODY: We conducted a PubMed search for all articles written in the English language about SARS-CoV-2 affecting the GI and liver. Following data extraction, 590 articles were selected. In addition to respiratory droplets, SARS-CoV-2 may reach the GI system through the fecal-oral route, saliva, and swallowing of nasopharyngeal fluids, while breastmilk and blood transmission were not implicated. Moreover, GI infection may act as a septic focus for viral persistence and transmission to the liver, appendix, and brain. In addition to the direct viral cytopathic effect, the mechanism of injury is multifactorial and is related to genetic and demographic variations. The most frequently reported GI symptoms are diarrhea, nausea, vomiting, abdominal pain, and bleeding. However, liver infection is generally discovered during laboratory testing or a post-mortem. Radiological imaging is the gold standard in diagnosing COVID-19 patients and contributes to understanding the mechanism of extra-thoracic involvement. Medications should be prescribed with caution, especially in chronic GI and liver patients. CONCLUSION: GI manifestations are common in COVID-19 patients. Special care should be paid for high-risk patients, older males, and those with background liver disease.

Post direct acting anti-viral agents associated primary hepatic Castleman's disease: A case report.

Castleman's disease (CD) is a primary lymphoproliferative disorder of the lymph nodes with rare extra-nodal primary affection. PRESENTATION OF CASE: Here we present a case of primary hepatic CD associated with hepatocellular carcinoma (HCC). DISCUSSION: Sixty-two years old, male received direct-acting antiviral agents (DAAs) for HCV infection. Follow up revealed sustained virologic response; however, three hepatic focal lesions were accidently discovered. Triphasic CT confirmed the HCC nature of two masses while the other mass remained undiagnosed. Surgical intervention was the treatment of choice, and pathological examination showed a fairly circumscribed mass formed of angiolymphoid hyperplasia displayed atrophic germinal center, expanded mantle zone, and variable hyalinization. The radiological evaluation of lymph nodes was unremarkable. The patient is 40 months alive after resection, with no further management advised. CONCLUSION: The immune-modulatory effect of DAAs may induce hepatic CD development in a cirrhotic patient, necessitating further studies. A new radiologic finding was observed in the present case in the form of vessels traversing through the lesion with no attenuation or occlusion. Pathology remains the gold standard in the diagnosis of CD.

Prognostic factors for long-term survival after pancreaticoduodenectomy for periampullary adenocarcinoma. A retrospective cohort study.

BACKGROUND: Periampullary adenocarcinoma (PAAC) had a poor prognosis, and pancreaticoduodenectomy (PD) remains the only potentially curative treatment. The study aimed to identify the impact of different clinicopathological factors on long-term survival following PD for PAAC. PATIENTS AND METHODS: This study is a retrospective cohort study for the patients who underwent PD for pathologically proven PAAC from January 2010 to January 2019. Statistical analysis was done using Cox regression multivariate analyses for independent risk factors for survival. RESULT: There were 137 patients with PAAC who underwent PD, 79 patients (57.7%) underwent pylorus-preserving PD. Pancreatico-jejunostomy was done in 108 patients (78.8%). The primary analysis showed that risk factors for poor long-term survival include patients with co-morbidities like hypertension or ischemic heart disease, Carbohydrate Antigen 19-9 > 400U/ml, tumor size > 3 cm, poor tumor differentiation, positive lymph nodes invasion, lymphovascular invasion, and Perineural invasion. Multivariate analysis demonstrated that large tumor size > 3 cm (HR: 0.177, 95%CI: 0.084-0.374, P = 0.002), poorly differentiated tumor (HR: 0.059, 95%CI: 0.020-0.0174, P = 0.016), and perineural invasion in the pathological study (HR: 0.101, 95%CI: 0.046-0.224, P = 0.006) were independent risk factors for poor 5-years survival. The prognosis was better in ampullary adenocarcinoma (5-year survival was 42.1%) than pancreatic adenocarcinoma (5-year survival was 24.3%). The 1, 3, 5 and 7-year overall survival rates were 84.5%, 57.4%, 35.9% and 20.1% respectively. CONCLUSION: It seems from the current study that Tumor size > 3 cm, poor tumor differentiation, and Perineural invasion were independent predictors of poor survival in patients with PAAC.

Nuclear BAP1 loss is common in intrahepatic cholangiocarcinoma and a subtype of hepatocellular carcinoma but rare in pancreatic ductal adenocarcinoma.

Deletion in the 3p21 region, the chromosomal location of BAP1, has been reported in a subset of hepatocellular carcinoma (HCC), biliary and pancreatic cancers. This suggests that BAP1 could play a role in the pathogenesis of these tumors. We assessed the frequency of BAP1 loss by immunohistochemistry in 103 hepatic, biliary and pancreatic cancers. We also assessed chromosomal alterations in the BAP1 region in the same tumors by genotyping. We identified high frequency 4/8 (50%) of BAP1 loss in intrahepatic cholangicarcinoma (ICC). However the frequency was lower in HCC 9/51 (17.6%), pancreatic 1/42(2.4%) and extrahepatic biliary cancers (0/2). Loss of heterozygosity of at least one marker from the 3p21 region was observed in 75% of ICC, 52.9% of HCC and 45.2% of pancreatic cancers. Expression of hepatocytic (HepPar1) and bile duct (cytokeratin 7) markers were common (7/9, 77.8%) in the HCC tumors with loss or decrease of BAP1 compared with those with preserved BAP1 (18/42, 42.9%), (Fisher exact p = 0.0751). Our results confirm the high frequency of BAP1 alterations in ICC and low frequency in pancreatic cancers. It also suggests that BAP1 is commonly altered in a subtype of HCC with both hepatocytic and biliary differentiation. Further studies of the therapeutic implications of our findings are warranted.

The Diagnostic Role of SPINK1 in Differentiating Hepatocellular Carcinoma From Nonmalignant Lesions.

BACKGROUND AND AIM: Distinction of small-sized hepatocellular carcinoma (HCC) from dysplastic nodules may be difficult. In addition, distinction of well-differentiated HCC (WD-HCC) from high-grade dysplastic nodule (HGDN) is also difficult in small needle biopsy. We aimed to study serine peptidase inhibitor, Kazal type 1 (SPINK1) immunohistochemical expression in HCC to differentiate it from nonmalignant lesions. METHODS: This study included 179 specimens from the archival material of Pathology Department, National Liver Institute, Menoufia University, between 2007 and 2014, divided as 93 HCC and 86 nonmalignant lesions. All cases were stained for SPINK1 antibody. RESULTS: SPINK1 was expressed in 76.3% of HCC cases with a diagnostic accuracy of 79.3%.There was a significant difference between focal nodular hyperplasia and WD-HCC cases regarding mean value of SPINK1 expression (P=0.015). In addition, there was low SPINK1 score in cirrhosis cases compared with WD-HCC. Moreover, there was a high significant difference between WD-HCC and HGDN regarding SPINK1 expression (P=0.001), with 83.3% sensitivity and 84.6% specificity. CONCLUSIONS: SPINK1 can be used to differentiate between a WD-HCC and a HGDN with high diagnostic validity.