Bcl-2 protein expression in acute and chronic hepatitis, cirrhosis and hepatocellular carcinoma

Bcl-2 protein blocks apoptosis and is involved in human intrahepatic bile-duct development. Formalin-fixed, paraffin-embedded archival tissue from 42 HBV and HCV hepatitis [20 acute AH, 22 chronic hepatitis (CH)], 12 active cirrhosis (CR) and 20 hepatocellular carcinoma (HCC) was immunostained for bcl-2 protein. In all cases, bcl-2 protein was detected in portal and intralobular lymphocytes but not in hepatocytes or Kupffer cells. Bcl-2 was positive in the cytoplasm of small portal bile ducts of chronic hepatitis, while it was strongly expressed in newly formed bile-ductules of the limiting plate, mainly in CH with marked activity and CR. Bcl-2 was detected in small bile ducts in only one case of acute hepatitis and was not detected in any case of HCC. Bcl-2 seems to be involved in the regulation of growth and apoptosis of cholangiolar cells. Its expression in small bile ducts and in newly-formed ductules especially in CH with marked activity and CR, implies that the embryonic model of intrahepatic bile duct development may be recapitulated in chronic hepatic disease. Moreover, it supports evidence for the existence of the controversial long-lived stem population in the liver. Bcl-2 does not seem to be involved in hepatocarcinogenesis.     

An immunocytochemical comparison of glial fibrillary acidic protein,S-100p and vimentin in human glial tumors

Immunostaining patterns of glial fibrillary acidic protein (GFAP), S-100 protein (S-100p) and vimentin were studied using immunohistochemical techniques on 48 paraffin embedded glial tumors. GFAP was positive in all tumor cases except in two oligodendrogliomas. S-100p was found in most astroglial tumors and in half of the oligodendrogliomas. Vimentin was positive in many astrocytomas but in no oligodendrogliomas. Most astroglial tumors showed similar immunoreactivity for GFAP and S-100p. Fibrillary processes, however, showed stronger and more crisp staining with anti-GFAP than with anti-S-100p, whereas cell nuclei were labeled only for S-100p. Vimentin was localised mainly in juxtanuclear positions.In many astrocytomas with different degrees of malignancy co-expression of GFAP, S-100p and vimentin was found. The presence of GFAP and S-100p was not correlated with the degree of differentiation in astrocytomas. Vimentin was more positive in anaplastic astrocytomas but this finding was not statistically significant. It seems that GFAP is a superior marker to S-100p and vimentin in the identification of human gliomas.     

The frequency of hepatitis B virus infection in Greek patients with various types of glomerulonephritis

The frequency of hepatitis B surface antigen (HBsAg) was studied in the sera of 622 patients with glomerulonephritis (GN). The prevalence of HBs-antigenemia was 2.8% (18/622; eleven adults and seven children); the difference from 2.6% in the general population of Central and Southern Greece was not statistically significant (²=0.01;p>0.50). Two of the 11 HBsAg-seropositive adult patients with GN suffered from IgA nephropathy, one from IgA and membranous glomerulonephritis (MGN), four from diffuse proliferative GN, two from membranous GN and one each from crescentic GN and focal segmental glomerulosclerosis. Five children out of 12 with membranous glomerulonephritis, one out of 24 with IgA nephropathy and one out of 16 with focal segmental glomerulosclerosis had HBs-antigenemia. The frequency of HBs-antigenemia in children with MGN was 41.7%, which is significantly higher than in children with others types of GN (0.9%). All seropositive patients were asymptomatic HBsAg carriers, while one seropositive HBsAg child with MGN suffered from chronic persistent hepatitis. HBsAg was detected by the immunoperoxidase-antiperoxidase (PAP) method in the glomeruli of only 3 children with MGN and HBs antigenemia, while HBcAg was not detected in any case. Our study suggests that in the Greek population there is no increased prevalence of HBs-antigenemia in patients with glomerulonephritis. Moreover, HBsAg was not found to contribute in the pathogenesis of GN in adults but it may be associated with the pathogenesis of membranous GN in children.     

Erectile dysfunction and premature ejaculation are the most frequently self-reported sexual concerns: profiles of 9,536 men calling a helpline

OBJECTIVES: To describe the range of sexual problems, as reported by men calling a help-line and to investigate factors associated with help seeking behaviour. METHODS: The study included all calls between 1999 and 2004. The information used for analysis comprised caller's demographic characteristics, the sexual problem reported, previous doctor contacts, coexisting physical and mental health problems. RESULTS: Erectile dysfunction (ED) and premature ejaculation (PE) were the most frequently reported problems (57 and 19.2% respectively). ED-reporting callers were older (OR 0.63 for the ages of 50-59 yrs), with co-morbidities (OR 1.75) and in stable relationship (OR 0.46), while PE-reporting callers were younger (OR 5.83 for the ages of 20-29 yrs), relatively healthy and more likely single (OR 2.62 and OR 2.92 respectively). Type and duration of sexual concern, age, coexisting health problems and marital status relate significantly (p<0.01) with willingness to seek medical help. CONCLUSIONS: The study demonstrates that ED and PE are men's major sexual concerns with personal and interpersonal factors influencing their help-seeking behaviour. Help-lines can serve as a link between health services and callers, while provide useful information for policy formation and improvement of support services.     

Effect of different ERK2 protein localizations on prognosis of patients with invasive breast carcinoma

Mitogen-activated protein kinase (MAP kinase) pathways represent a cascade of phosphorylation events, including three pivotal kinases, Raf, MEK and ERK1/2, which have been implicated in the pathogenesis of cancer. We examined 151 cases of invasive breast carcinoma by immunohistochemistry and compared the ERK2 expression with clinicopathological parameters, MMP-11 immunoexpression and patients' survival. ERK2 immunoexpression was detected in the cytoplasm and nucleus of cancer cells in 37.7% and 19.2% of cases, respectively. Nuclear ERK2 was inversely correlated with ER (p = 0.039), whereas cytoplasmic ERK2 was positively correlated with MMP-11 in fibroblasts (p = 0.032) and more often expressed in lobular than ductal carcinomas (p = 0.026). Nuclear ERK2 expression was found to be an independent prognostic factor of shortened overall survival of patients (p = 0.040), while cytoplasmic ERK2 had an independent, favorable effect on both disease-free and overall survival (p < 0.0001 and p = 0.002, respectively). These findings suggest that the different subcellular localizations of ERK2 seem to be related to different, possibly contradictory, effects on patient survival.     

Demonstration of alpha1-antitrypsin in paraffin sections of hepatoma and cirrhosis

Summary Alpha₁-antitrypsin has been examined in formalin-fixed, paraffin-embedded liver specimens from Greek patients with cirrhosis (35 cases) and hepatoma (55 cases) by peroxidase-antiperoxidase (PAP) method. Ring-like AAT globules were found in the non-neoplastic cells in 12% of the cases of hepatoma and in 11% of the cases of cirrhosis. Atypical globules were seen in neoplastic cells in 5.4% of the cases of hepatoma and in 17% of the cases of liver cirrhosis. A diffuse fine granular pattern of AAT distribution was present in 31% of the cases of hepatoma in the neoplastic cells and in 27% of those in the nonneoplastic cells. The relatively high incidence of ring-like AAT-globules, and of atypical globules in cases of hepatoma and cirrhosis is not in agreement with the extremely low gene frequency of Z allele in a Greek population of patients with cirrhosis and hepatoma. Thus, there is some doubt whether AAT-globules in the liver represent a histopathologic marker of genetically determined AAT deficiency. A relationship between AAT deposits and the degree of differentiation of hepatoma was noted in this series. AAT-positive cells were found in 55% of moderately differentiated, in 29% of highly differentiated and in 20% of poorly differentiated hepatomas.     

Abnormal alpha-catenin expression in invasive breast cancer correlates with poor patient survival

AIMS: alpha-Catenin is a member of the E-cadherin-catenin family of adhesion molecules whose role is essential for the function of the E-cadherin complex. In this study, we have evaluated the expression of alpha-catenin but also of the other catenins (beta-, gamma- and p120-catenin) and E-cadherin in invasive breast cancer and statistically analysed these expressions with known clinicopathological parameters, c-erbB-2 oncoprotein expression and patient survival. METHODS AND RESULTS: Abnormal E-cadherin and beta-catenin expression, especially loss of expression, was associated with lobular histological type of breast carcinomas (P=0.03 and P=0.01, respectively). Abnormal E-cadherin and alpha-catenin expression was associated with high histological grade ductal carcinomas (P=0.01 and P=0.03, respectively). Abnormal E-cadherin and beta-catenin expression was correlated with lymph node metastases (P=0.02 and P=0.05, respectively), while abnormal alpha- and beta-catenin were correlated with the advanced stage of the disease (P=0.04 and P=0.05, respectively). Abnormal p120-catenin expression was associated with loss of PR (P=0.008). Survival analysis demonstrated a statistically significant association between abnormal alpha-catenin expression and poor patient survival (P=0.02). When survival analysis was performed according to the different patterns of abnormal expression, statistically significant associations were seen between cytoplasmic alpha- and beta-catenin expression and poor survival (P=0.006 and P=0.04, respectively). CONCLUSIONS: alpha-Catenin, especially its cytoplasmic expression, seems to be a more sensitive prognostic marker than the other members of the E-cadherin complex in invasive breast cancer.     

Matrix metalloproteinase-1 and -3 in breast cancer: correlation with progesterone receptors and other clinicopathologic features

Although matrix metalloproteinases (MMPs) are implicated in breast cancer progression, the contribution of MMP-1 and MMP-3 to this process, has not been thoroughly investigated. Matrix metalloproteinases (MMPs) are important at several points during multistage neoplastic progression. Immunohistochemistry (Strept-ABC-HRP method) and in situ hybridization were performed to detect MMP-1, MMM-3 proteins, and MMP-3 mRNA, respectively, in 77 infiltrative breast carcinomas. MMP-1, MMP-3 protein, and MMP-3 mRNA detection were analyzed in parallel with clinicopathologic features (menopausal status, histological type, nuclear and histological grade, stage) and the immunohistochemical reactivity of estrogen (ER), progesterone (PR) receptors, and c-erbB-2 oncoprotein in breast carcinomas. Statistical analysis was performed using the multiple linear regression test. Immunoreactivity for MMP-1 and MMP-3 was observed in 59 of 77 (77%) and 22 of 77 (28.5%) breast carcinomas and was evaluated separately in cancer cells and in stromal fibroblasts. MMP-3 mRNA was detected in 72 of 77 (93.5%) carcinomas exclusively in stromal cells within the tumors or in the marginal portion of tumors. MMP-1 protein immunoreactivity in stromal fibroblasts but not in cancer cells showed a statistically significant correlation with tumor stage (P=.04). MMP-1 reactivity either in stromal or in cancer cells showed a statistically significant inverse correlation with PR expression (P=.04 and P=.04, respectively). MMP-3 protein immunoreactivity in cancer or stromal cells and MMP-3 mRNA expression was not associated with the clinicopathologic features studied. MMP-3 mRNA was detected more often in ductal carcinomas. These results indicate that MMP-1 may contribute to breast cancer invasiveness. Furthermore, they suggest differential functions for MMP-1 and MMP-3 in breast cancer progression.