The role of hepatic progenitor cells in predicting response to therapy in Egyptian patients with chronic hepatitis C, genotype 4.

BACKGROUND: Interferon therapy is used as a line of treatment of chronic hepatitis C virus (HCV) in several areas of the world including Egypt. OBJECTIVE: Our aim was to investigate the value of hepatic progenitor cells (HPCs) in predicting response of patients with chronic HCV, genotype 4 to pegylated interferon (PEGIFN) plus ribavirin (RBV) therapy. METHODS: Pre-treatment liver biopsies obtained from 110 patients with chronic HCV, genotype 4 were examined immunohistochemically for HPCs using cytokeratin19. The mean number of HPCs as ductular reaction (DR) and as isolated progenitor cells (IPCs) was counted in each case. The patients were classified into: those with sustained virological response (SVR) and those who did not achieve SVR. The results were compared between the two groups. Also, the relationships between HPCs and other clinico-pathologic variables were estimated using multivariate analysis. RESULTS: The mean number of HPCs was the only independent predictor of therapeutic response, being significantly higher in non-responders (P = 0 for DR and P = 0.03 for IPCs). On the other hand, fibrosis stage and steatosis were the only independent factors which showed a significant direct association with the mean number of HPCs in the form of DR and IPCs (P = 0 for each). CONCLUSION: The number of HPCs provides prognostic information in chronic HCV since it is significantly associated with stage of fibrosis. More importantly, it can be used as a marker to predict response of patients with chronic HCV to PEGIFN plus RBV therapy.

The role of E-cadherin and Runx3 in Helicobacter Pylori - Associated gastric carcinoma is achieved through regulating P21waf and P27 expression.

BACKGROUND: We assessed the role of E-cadherin (CDH1), runt-related transcription factor 3, p21waf and p27 promoter methylation (PM) and protein expression in Helicobacter pylori (HP)-associated gastric carcinomas (GCs) and adjacent non-neoplastic tissues (ANNTs). PATIENTS AND METHODS: 192 cases were assessed for PM and protein expression of CDH1, RUNX3, p21waf and p27 by methylation-specific PCR (MSP) and immunohistochemistry. The CagA gene was also assessed. RESULTS: In GCs, 66 (34.4%) and 84 (43.8%) cases showed CDH1-PM and reduced expression. It is significantly affected in GCs rather than in non-neoplastic groups (p < 0.001). In ANNTs, 108 (56.3%) cases showed CDH1-PM and all cases revealed preserved protein expression. RUNX3-PM was detected in 78 GCs (40.6%) and 69 ANNTs (35.9%), whereas reduced protein expression was detected in 99 (51.65%) GC compared to ANNTs 90 (46.9%). p21WAF and p27 showed PM in (48.4% and 45.3%) GCs and ANNTs; respectively. p21waf protein was reduced in 90 (46.9%) cases and 91 ANNTs (47.4%). p27 was reduced in 86 (44.8%) cases and 87 ANNTs (45.3%). CDH1 aberrations correlated with HP in tumors and ANNTs and with diffuse/intestinal tumors (p = 0.014, p = 0.014 and p = 0.02). RUNX3 aberrations associated with HP (p = 0.04), high grade (p = 0.04), and advanced stage (p = 032). Tumor grade associated with RUNX3-PM, CDH, p21 and p27 protein (p < 0.05 for all). Tumor stage associated significantly with PM and reduced protein expression of all markers. Positive lymph nodes associated significantly with p27PM (p < 0.001). CONCLUSIONS: HP plays an important role in the development and progression of GC through silencing of CDH1, RUNX3, p21WAF and p27 expression.

Idiopathic Granulomatous Mastitis: Cytologic and Histologic Study of 65 Egyptian Patients.

BACKGROUND: The etiology of idiopathic granulomatous mastitis (IGM) is unknown, and it is commonly misdiagnosed clinically and/or radiologically as breast cancer. The role of fine-needle aspiration cytology (FNAC) in its diagnosis is still a matter of debate. The aim of the current study is to assess the value of FNAC in the diagnosis of IGM, and to search for the presence of bacteria in IGM with cystic vacuoles, which was described recently by a few authors. MATERIALS AND METHODS: Retrospective study of cytologic smears and histologic tissue sections of 65 Egyptian IGM cases was done along with microbiologic testing. A comparison of the frequency of IGM in Egypt to that of other populations was also made. RESULTS: IGM has typical FNA features which can easily exclude malignancy. Histologically, cystic vacuoles were encountered in 35 out of 65 cases (53.9%), with only 6 (17.14%) of these cases showing Gram-positive bacilli (GPB). The frequency of IGM in Egypt is comparable to those in other Middle Eastern countries but much higher than in Western countries. CONCLUSION: IGM is a common breast disease in Egypt. FNAC in IGM has a high diagnostic accuracy. This study supports the few recent studies that have detected GPB in IGM with cystic vacuoles. Thus, bacteriologic examination in such cases may affect the treatment strategy.

Extrahepatic metastases as initial manifestations of hepatocellular carcinoma: an Egyptian experience.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) in Egypt has markedly increased in the recent years, mainly due to the high incidence of hepatitis C virus (HCV) infection. Consequently, the frequency of metastatic HCC has also increased. The current study presents a series of 47 patients who were initially diagnosed as metastatic HCC. METHODS: Forty seven patients with the diagnosis of extrahepatic metastases of HCC at initial presentation were included in the study. The sites of metastases were bones (17), lymph nodes (9), soft tissue (7), omentum (7), maxillary sinus (2), adrenal gland (2), brain (2) and skin (1). The diagnosis of metastatic HCC was confirmed by immunohistochemistry. RESULTS: The patients included in the study were 38 males and 9 females, ranging from 40 to 80 years (median 60 years). All patients were HCV-positive and 36 were cirrhotic. The diagnosis of primary HCC was confirmed in all cases, based on the typical hypervascular radiological features and/or high serum α-fetoprotein concentration, or histologic examination of liver biopsy. CONCLUSION: Metastasis of HCC should be put into consideration when evaluating metastatic carcinoma with unknown primary. This is of particular importance in the Egyptian population who has the highest prevalence of HCV infection in the world.

Role of alpha methylacyl-coenzyme A racemase in differentiating hepatocellular carcinoma from dysplastic and nondysplastic liver cell lesions.

Distinction of hepatocellular carcinoma (HCC) from liver cell dysplasia (LCD) is one of the problems faced by pathologists. In spite of various methods claimed to differentiate between these 2 lesions, no reliable marker is available until now. The aim of the study was to assess the value of alpha methylacyl-coenzyme A (COA) racemase (AMACR) in distinguishing HCC from LCD. Formalin-fixed, paraffin-embedded tissue sections from 30 HCCs and 30 nonneoplastic liver tissues (12 dysplastic and 18 nondysplastic lesions) were immunostained for AMACR. Staining intensity was interpreted as low (negative, mild) and high expressions (moderate, marked). Alpha methylacyl-COA racemase showed high expression in 21 (70%) of 30 HCCs and 7 (58.3%) of 12 LCDs. All 18 nondysplastic lesions revealed low AMACR expression. The percentage of high AMACR expression was significantly more in HCC and LCD as compared with nondysplastic lesions (P = .001 in each). There was no significant difference in AMACR expression between HCC and LCD. Furthermore, the pattern of AMACR immunostaining was coarsely granular cytoplasmic positivity in HCC as well as LCD in comparison with the weak finely granular in nondysplastic lesions. Alpha methylacyl-COA racemase cannot discriminate HCC from LCD, although it can separate HCC and LCD from nondysplastic lesions.

Immunoexpression of p53 and hMSH2 in oral squamous cell carcinoma and oral dysplastic lesions in Yemen: relationship to oral risk habits and prognostic factors.

Although several studies analyzed p53 and mismatch repair (MMR) gene expression separately in oral squamous cell carcinoma (SCC), no reports of combined assessment of both proteins in this cancer. The aim of this study was to investigate the roles of p53 and hMSH2 proteins in oral SCC as well as in oral dysplastic lesions (DL) in Yemen. Immunohistochemistry was used to examine the pattern of expression of p53 and hmsh2 proteins in 70 oral SCC and 21 oral DL obtained from Yemeni patients. p53 Immunoexpression was detected in 24 of the 70 oral SCC (34.3%) and 3 of 21 DL (14.3%) with no significant difference between the two groups. On the other hand, reduced expression of hMSH2 was detected in 26 of the 70 oral SCC (37.1%) and 2 of 21 oral DL (9.5%) with a statistically significant difference (P=0.03). Both proteins were significantly related to the grade of tumor differentiation (P=0.007 and 0.02, respectively). There was an inverse correlation between the levels of p53 and hMSH2 immunoexpression in the oral SCC (r=0.42, P=0.01). This study suggested that p53 may play a role in the early stages of oral carcinogenesis, while hMSH2 may be altered in the late stages. More importantly, the roles of p53 and hMSH2 in oral carcinogenesis seem to be interrelated in the pathogenetic pathway of oral SCC. Such a relationship has not been published previously in this type of cancer and needs to be clarified in future studies.

Human papilloma virus and p53 expression in bladder cancer in Egypt: relationship to schistosomiasis and clinicopathologic factors.

The aim of the current study was to compare the role of p53 and human papillomavirus (HPV) in schistosomiasis-related and schistosomiasis-unrelated carcinoma of the urinary bladder. To achieve this aim, we investigated 114 bladder carcinomas for p53 oncoprotein expression by immunohistochemistry and for human papillomavirus by in situ hybridization technique. The results revealed that 64 tumors (56.1%) were schistosomiasis-associated. Sixty seven (58.8%) were transitional cell carcinomas and 32 (28%) were squamous cell carcinomas. The remaining 15 tumors (13.2%) included adenocarcinomas and sarcomatoid carcinomas. In both schistosomiasis-associated and non-associated carcinomas, p53 oncoprotein expression was significantly higher in poorly differentiated tumors. However, it was significantly higher in locally more invasive tumors in the schistosomal carcinomas only. HPV types 16/18 could be detected in 1 of the 114 bladder carcinomas (0.95%), which was schistosomiasis-related squamous cell carcinoma in situ. These results suggest that p53 immunohistochemistry can be a prognostic factor in both schistosomal and nonschistosomal bladder cancer. More importantly, HPV does not seem to play a role in the pathogenesis of either type of bladder cancer in our country.

Immunophenotyping of tumor-infiltrating mononuclear cells in ovarian carcinoma.

Infiltrating mononuclear cells play an important role in many types of cancer. The aim of this work was to determine the immunologic characteristics of mononuclear cellular infiltrate in ovarian cancer as compared to benign ovarian tumors. Paraffin-embedded tissues obtained from 52 ovarian carcinomas and 21 benign ovarian neoplasms were examined immunohistochemically to demonstrate suppressor/cytotoxic T cells and macrophages by using CD8 and CD68 monoclonal antibodies, respectively. The mean percentage of CD8+ cells was much higher in the malignant than in the benign group (P=0.00009). Similarly, the mean level of CD68+ cells was significantly higher in carcinomas than in benign cases (P=0.006). There was a significant negative correlation between the percentage of CD8+ cells and CD68+ cells in the malignant group (P=0.000002). Conversely, no correlation could be obtained between the values of these two cell types in the benign lesions. In the malignant group, although the percentages of CD8+ cells and CD68+ cells were not related to tumor differentiation, they were significantly related to tumor type. CD8+ cells were significantly higher in the serous (P=0.02), and CD68+ cells were higher in the mucinous carcinomas (P=0.0005). CD8+ T cells and macrophages constitute a major component of the infiltrating mononuclear cells in ovarian carcinoma. Their frequency seems to be related to the tumor type rather than the degree of tumor differentiation.