Cyclic neutropenia and concomitant IgA nephropathy: a case report.

BACKGROUND: IgA nephropathy (IgAN) is universally recognized as one of the most common primary glomerular diseases in all ages. Cyclic neutropenia (CN) is a rare haematologic disorder that is associated with mutations of the ELANE gene. The co-occurrence of IgAN and CN is extremely rare. This is the first case report of a patient with IgAN and genetically confirmed CN. CASE PRESENTATION: We report a case of a 10-year-old boy who presented with recurrent viral upper respiratory tract infections accompanied by several episodes of febrile neutropenia, haematuria, proteinuria and acute kidney injury. Upon first admission, his physical examination was unremarkable. His kidney function was impaired, whereas his urine microscopy showed evidence of macroscopic haematuria and proteinuria. Further workup showed elevated IgA. The renal histology was consistent with mesangial and endocapillary hypercellularity with mild crescentic lesions, while immunofluorescence microscopy showed IgA-positive staining, which was characteristic of IgAN. Moreover, genetic testing confirmed the clinical diagnosis of CN, therefore Granulocyte colony-stimulating factor (G-CSF) was initiated to stabilize the neutrophil count. Regarding proteinuria control, the patient was initially treated with an Angiotensin-converting-enzyme inhibitor for approximately 28 months. However, due to progressive proteinuria (> 1 g/24 h), Corticosteroids (CS) were added for a period of 6 months according to the revised 2021 KDIGO guidelines with favorable outcome. CONCLUSIONS: Patients with CN are more susceptible to recurrent viral infections, which can trigger IgAN attacks. In our case CS induced remarkable proteinuria remission. The use of G-CSF contributed to the resolution of severe neutropenic episodes, viral infections and concomitant AKI episodes, contributing to better prognosis of IgAN. Further studies are mandatory to determine whether there is a genetical predisposition for IgAN in children with CN.

Generation of a novel decay accelerating factor (DAF) knock-out rat model using clustered regularly-interspaced short palindromic repeats, (CRISPR)/associated protein 9 (Cas9), genome editing.

Decay accelerating factor (DAF), a key complement activation control protein, is a 70 kDa membrane bound glycoprotein which controls extent of formation of the C3 and C5 convertases by accelerating their decay. Using clustered regularly-interspaced short palindromic repeats, (CRISPR)/associated protein 9 (Cas9) genome editing we generated a novel DAF deficient (Daf-/-) rat model. The present study describes the renal and extrarenal phenotype of this model and assesses renal response to complement-dependent injury induced by administration of a complement-fixing antibody (anti-Fx1A) against the glomerular epithelial cell (podocyte). Rats generated were healthy, viable and able to reproduce normally. Complete absence of DAF was documented in renal as well as extra-renal tissues at both protein and mRNA level compared to Daf+/+ rats. Renal histology in Daf-/- rats showed no differences regarding glomerular or tubulointerstitial pathology compared to Daf+/+ rats. Moreover, there was no difference in urine protein excretion (ratio of urine albumin to creatinine) or in serum creatinine and urea levels. In Daf-/- rats, proteinuria was significantly increased following binding of anti-Fx1A antibody to podocytes while increased C3b deposition was observed. The DAF knock-out rat model developed validates the role of this complement cascade regulator in immune-mediated podocyte injury. Given the increasing role of dysregulated complement activation in various forms of kidney disease and the fact that the rat is the preferred animal for renal pathophysiology studies, the rat DAF deficient model may serve as a useful tool to study the role of this complement activation regulator in complement-dependent forms of kidney injury.

Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib.

Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD (P=0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P=0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.

Audit of cytology of upper urinary tract.

OBJECTIVE: Cytology is an essential tool for the investigation of urinary tract malignancy. In this audit, we aimed to assess our laboratory performance in the diagnosis of upper urinary tract malignancy and to use the information provided to improve our service. METHODS: We retrieved cytology reports of upper urinary tract specimens from two periods, re-evaluated the cases, compared the reports with histology data and estimated the sensitivity, specificity and positive predictive value (PPV). In the time interval between the two periods, we adopted new terminology, established better communication with clinicians and gained experience in the field. Finally, the data from the two periods were compared. RESULTS: In phase A, we estimated a sensitivity of 73%, specificity of 86% and PPV of 84.6%. As a result of the cytological re-evaluation, correlation with histology and clinical follow-up, plus communication with the clinicians during the audit, we established new terminology and a new request form. A three tiered grading system of atypia (mild, moderate and severe) was replaced by a two tiered grading system. The first category "atypia probably benign" corresponded to "mild atypia" while the second category "atypia, not otherwise specified" corresponded to "moderate atypia". The cases diagnosed as "severe atypia" were reclassified as "suspicious for malignancy". In phase B, the sensitivity, specificity and PPV were 75%, 89% and 90%, respectively. CONCLUSIONS: Our laboratory performance is in concordance with reported data and has been improved through this study. The audit process is extremely valuable for the identification of problems, for taking action and, finally, for the improvement of the clinical cytology service in the field of upper urinary tract malignancy.

Expression of Ser729 phosphorylated PKCepsilon in experimental crescentic glomerulonephritis: an immunohistochemical study.

PKCε, a DAG-dependent, Ca2+- independent kinase attenuates extent of fibrosis following tissue injury, suppresses apoptosis and promotes cell quiescence. In crescentic glomerulonephritis (CGN), glomerular epithelial cells (GEC) contribute to fibro-cellular crescent formation while they also transdifferentiate to a mesenchymal phenotype. The aim of this study was to assess PKCε expression in CGN. Using an antibody against PKC-ε phosphorylated at Ser729, we assessed its localization in rat model of immune-mediated rapidly progressive CGN. In glomeruli of control animals, pPKCε was undetectable. In animals with CGN, pPKCε was expressed exclusively in glomerular epithelial cells (GEC) and in GEC comprising fibrocellular crescents that had acquired a myofibroblast-type phenotype. In non-immune GEC injury induced by puromycin aminonucleoside and resulting in proteinuria of similar magnitude as in CGN, pPKCε expression was absent. There was constitutive pPKCε expression in distal convoluted tubules, collecting ducts and thick segments of Henley's loops in both control and experimental animals. We propose that pPKCε expression occurring in GEC and in fibrocellular crescentic lesions in CGN may facilitate PKCε dependent pathologic processes.

Lupus nephritis and non-Hodgkin lymphoma simultaneously diagnosed in a patient on methimazole.

A 78 year old white male on methimazole due to Grave's thyroiditis presented with acute renal failure after a short term history of progressive shortness of breath, malaise, myalgias, arthralgias, and bilateral lower limb swelling. The abdomen was remarkable for splenomegaly and lower extremities for erythema nodosum. No peripheral lymphadenopathy was detected. Serum albumin was 1.7 g/dl and very high erythrocyte sedimentation rate. Urine sediment was very active with dysmorphic red blood cells and casts and significant proteinuria (6.6 grams/day). Serum complements were abnormally low and antinuclear and anti-DNA antibodies were positive. Renal histopathology revealed membranoproliferative glomerulonephritis, along with a full house pattern on IFF consistent with lupus nephritis. Bone marrow aspiration revealed a 40% infiltration by a lymphocyte population of small cells consistent with a B cell non-Hodgkin lymphoma. The patient was treated with methylprednisolone, cyclophosphamide and rituximab and acute dialysis. Over the following weeks the patient became dialysis independent and returned to his baseline GFR.

Clinical implications of the histologically and immunohistochemically detected solitary lymph node metastases in gastric cancer.

BACKGROUND: Topographic correlation between the primary gastric tumor and the first peri- and extragastric lymphatic drain basin (solitary lymph node metastasis) on gastrectomy specimens, represents a reliable method to investigate and understand the exact pattern of lymphatic drainage from a gastric tumor. Analyzing that correlation, useful information regarding the extent of the appropriate oncological perigastric lymphadenectomy will be provided. We retrospectively evaluate the usefulness of a modified D2 lymphadenectomy in gastric cancer patients, based on the topographic correlation between the primary tumor and the location of the solitary lymph node metastases, as they were detected by histology and immunohistochemistry. MATERIALS AND METHOD: Between April 2003 and March 2010, 134 gastric cancer patients were submitted to a modified D2 lymphadenectomy. Postoperatively, the standard histological ex-amination by hematoxylin and eosin (HE) staining, disclosed metastatic infiltration of at least two lymph nodes in 90 patients, solitary lymph node metastases were histologically detected in 10 patients, while the remaining 34 patients were classified as pN0. All lymph nodes of the ten patients with histological solitary lymph node metastases, as well as the 34 patients who had been classified as pN0 by histology, were further submitted to immunohistochemistry for micrometastases detection. More than one micrometastases were detected in none of them, while in seven patients solitary micrometastases were detected either in the level I perigastric or in the level II extragastric lymph nodes stations (skip micrometastases). RESULTS: Solitary lymph node metastases were detected by histology in ten patients and by immunohistochemistry in additional seven (nine females and eight males). Solitary metastases were detected in the level I LN stations in seven patients (four by histology and three by immunohistochemistry) and in the level II LN stations in ten patients (six by histology and four by immunohistochemistry). In order of frequency, the solitary lymph node metastases were located in the no 7 (n = 6), no 6 (n = 4), no 9 (n = 2), no 5 (n = 2), no 4 (n = 1), no 8 (n = 1) and no 12 (n = 1) LN stations. Skip metastases encountered the 60% of the histologically detected, 57% of the immunohistochemically detected and 59% of all solitary lymph node metastases. 80% of solitary metastases in the level II LN stations, were mainly located in the nos 7-9 lymph node stations complex. Tumors of the lower and middle-third of the stomach were equally drained both to the level I and level II lymph node stations, while 67% of the tumors towards the lesser curvature, were mainly drained in the level II lymph node stations. CONCLUSION: D2 lymphadenectomy increases the number of true R0 resections. Thus, a modified D2 lymphadenectomy should be routinely performed in gastric cancer patients.

Comparative study of the immunohistochemical expression of metalloproteinases 2, 7and 9between clearly invasive carcinomas and "in situ" trophoblast invasion.

KEYWORDS: Matrix metalloproteinases (MMPs) are endopeptidases considered to participate in the transient invasive property of trophoblastic cells during embryo implantation and placentation. The same molecules play an important role in the invasive and metastatic potential of cancer cells. The aim of this study was to compare the immunohistochemical expression of MMP2, 7and 9between clearly invasive carcinomas and "in situ" trophoblast invasion in an effort to illuminate their distinct roles in uncontrolled and controlled invasion.
We performed an immunohistochemical analysis of 45 clearly invasive carcinomas of various organs (colorectal, gastric, breast, pulmonary, renal) and 40 first trimester gestation specimens (before the 9th week of gestation). The markers expression was evaluated semiquantitavely, seperately in cancer parenchymal and gestational trophoblastic cells as well as cancer stromal and decidual cells, according to apercentage scale (0 %, 50% of cells) and according to staining intensity (0, +, ++, +++).
MMP9 was expressed more often in the malignant parenchymal as well as in the malignant stromal component of carcinomas than in the trophoblastic (p=0, 0118) and decidual (p=0,017) component of gestations respectively. Although all carcinomas and almost all gestation specimens stained for MMP2 and MMP7, the immunostaining for both molecules was statistically more extensive and intense in trophoblasts and decidual cells by comparison to cancerous elements.
In conclusion, although there seems to be adirect link between cancer invasion and MMP9 immunohistochemical expression, the role of MMP2 and MMP7 appears to be more complicated underlining the complexity of the mechanisms involved in cancer spreading.

Liver histology alterations during carbon dioxide pneumoperitoneum in a porcine model.

BACKGROUND: This study aimed to investigate the time course changes in liver histology during carbon dioxide (CO(2)) pneumoperitoneum in a large animal model. METHODS: For this study, 14 white pigs were anesthetized. Liver biopsies performed 0, 1, and 2 h after establishment of CO(2) pneumoperitoneum (at 12 mmHg) and after peritoneal desufflation were sent for histologic examination. Heart rate, mean blood pressure, hepatic artery flow, portal vein flow, and aortic flow were recorded in 10-min increments. Three animals served as control subjects. RESULTS: A statistically significant time course increase was observed in portal inflammation, intralobular inflammation, edema, sinusoidal dilation, sinusoidal hyperemia, centrilobular dilation, centrilobular hyperemia, pericentrilobular ischemia, and focal lytic necrosis scores. There were no significant changes in the control group. This eliminated an effect of anesthesia only. The portal vein flow increased as much as 21%, and the hepatic artery flow decreased as much as 31% of baseline, but these differences did not attain statistical significance. Aortic flow remained relatively stable. CONCLUSION: Histomorphologic changes occurred, indicating liver tissue injury during CO(2) pneumoperitoneum at an intraabdominal pressure of 12 mmHg in the porcine model. Portal vein flow increased, and hepatic artery flow decreased, whereas aortic flow remained relatively unaffected in this experiment.

Minichromosome maintenance proteins 2 and 5 in non-benign epithelial ovarian tumours: relationship with cell cycle regulators and prognostic implications.

Minichromosome maintenance proteins (MCM) have recently emerged as novel proliferation markers with prognostic implications in several tumour types. This is the first study investigating MCM-2 and MCM-5 immunohistochemical expression in a series of ovarian adenocarcinomas and low malignant potential (LMP) tumours aiming to determine possible associations with clinicopathological parameters, the conventional proliferation index Ki-67, cell cycle regulators (p53, p27(Kip1), p21(WAF1) and pRb) and patients' outcome. Immunohistochemistry was applied in a series of 43 cases of ovarian LMP tumours and 85 cases of adenocarcinomas. Survival analysis was restricted to adenocarcinomas. The median MCM-2 and MCM-5 labelling indices (LIs) were significantly higher in adenocarcinomas compared to LMP tumours (P<0.0001 for both associations). In adenocarcinomas, the levels of MCM-2 and MCM-5 increased significantly with advancing tumour stage (P=0.0052 and P=0.0180, respectively), whereas both MCM-2 and MCM-5 increased significantly with increasing tumour grade (P=0.0002 and P=0.0006, respectively) and the presence of bulky residual disease (P<0.0001 in both relationships). A strong positive correlation was established between MCM-2 or MCM-5 expression level and Ki-67 LI (P<0.0001) as well as p53 protein (P=0.0038 and P=0.0500, respectively). Moreover, MCM-2 LI was inversely correlated with p27(Kip-1) LI (P=0.0068). Finally, both MCM-2 and MCM-5 were associated significantly with adverse patients' outcome in both univariate (> or =20 vs >20%, P=0.0011 and > or =25 vs <25%, P=0.0100, respectively) and multivariate (P=0.0001 and 0.0090, respectively) analysis. An adequately powered independent group of 45 patients was used in order to validate our results in univariate survival analysis. In this group, MCM-2 and MCM-5 expression retained their prognostic significance (P<0.0001 in both relationships). In conclusion, MCM-2 and MCM-5 proteins appear to be promising as prognostic markers in patients with ovarian adenocarcinomas.

Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas.

Caspase-3 is the ultimate executioner caspase that is essential for the nuclear changes associated with apoptosis. We investigated caspase-3 immunohistochemical expression in 58 primary intracranial meningiomas, using one monoclonal antibody detecting both precursor and cleaved caspase-3 (CPP32) and a second recognizing only the cleaved activated form (ASP175). Caspase-3 expression was analyzed in relation to baseline apoptosis-as illustrated by the expression of anti-single stranded DNA (ss-DNA), the antiapoptotic protein bcl-2, proliferation indices (Ki-67, PCNA, topoisomerase IIa, mitosin C), hormonal status (estrogen, progesterone, androgen receptors), standard clinicopathological parameters and patients' disease-free survival. Caspase-3 immunostaining was observed in 62% of cases for CPP32 and in 24% for ASP175. In both instances, the labeling index (LI) was significantly correlated with ss-DNA LI (p=0.038 and p=0.018). CPP32 but not ASP175 LI positively correlated with the mitotic index (p=0.001) and PCNA LI (p=0.004). Both CPP32 and ASP175 LIs were increased in nonbenign meningiomas (p<0.0001 and p=0.0035 respectively). In univariate and multivariate survival analyses, caspase-3 predicted meningioma recurrence, independently affecting disease-free survival (p=0.011 and p=0.047 respectively for CPP32; p<0.0001 and p=0.012 respectively for ASP175). Caspase-3 may prove to be a useful predictor of early recurrence in a group of neoplasms characterized by the frequent discordance between histology and clinical behavior.

Tenascin-C protein expression and mRNA splice variants in thyroid carcinoma.

Tenascin-C (Tn-C) is a matricellular protein involved in the initial and intermediate stages of cell adhesion. The present study is the first undertaken to comparatively investigate Tn-C in neoplastic, non-neoplastic thyroid lesions and normal thyroid tissues. Forty-eight thyroid specimens were studied immunohistochemically using a monoclonal antibody against Tn-C. Immunohistochemistry was supplemented by RT-PCR analysis of the two Tn-C mRNA splice variants in 13 thyroid cancer cell lines. Normal and non-neoplastic tissues were devoid of Tn-C, as well as follicular neoplasms, Huerthle-cell and anaplastic carcinomas. Most papillary carcinomas showed a focally intensive extracellular staining, localized in the connective tissue stroma, whereas most medullary carcinomas showed a staining in the connective tissue but also in intracellular location mainly. RT-PCR analysis detected Tn-C mRNA in all thyroid cancer cell lines with prevalence of the large splice variant in all but the medullary line, characterized by a higher Tn-Csmall:Tn-Clarge ratio. In conclusion, Tn-C re-expression has been observed in papillary and medullary thyroid carcinomas with different staining patterns accompanied by the prevalence of different mRNA splice variants in cell cultures. It seems possible that Tn-C is rather synthesized by tumor cells than by activated stromal cells.

Sequential recurrences of ovarian granulosa cell tumour 10 and 11 years after initial diagnosis as haemoperitoneum and subhepatic mass: a case report and review of the literature.

Adult granulosa cell tumours (GCTs) are rare ovarian neoplasms characterised by an indolent course and a propensity for late recurrence. Due to frequent endocrine manifestations most GCTs are diagnosed at an early stage. However, clinical behaviour can not be safely predicted on the basis of conventional clinicopathologic parameters. Surgery remains the cornerstone of therapeutic management. We report on a rare case of a Stage IA GCT twice recurring ten and 11 years after initial surgical treatment. The first recurrence presented as an acute abdomen due to haemoperitoneum after tumour rupture. The second recurrence presented as a subhepatic mass. This case emphasises the need for extended, lifelong follow-up even for patients with early stage, apparently completely removed GCTs. Prognostic parameters and therapeutic options especially for patients with recurrent disease are discussed.

Sarcomas of the head and neck. Results from the treatment of 25 patients.

AIMS: Head and neck sarcomas comprise a heterogenous and biologically diverse group of rare neoplasms. In an effort to clarify some of the obscure clinical behavior of head and neck sarcomas, we present our experience and review the relevant literature. METHODS: Retrospective analysis of patients with histologically proven head and neck sarcomas treated in a tertiary Hospital Department between 1992 and 2002. RESULTS: During this period, 25 patients with head and neck sarcomas were registered. Follow-up ranged from 8 to 144 months. Twenty-three patients were treated with surgery as the primary modality; 14 were treated by surgery alone. Clear margins were obtained in all of them and local control was achieved in 12/13. The 2- and 5-year survival rates for the entire group were 80 and 40%, respectively. Mean overall survival time of our patients was 62 months (median 52 months). CONCLUSIONS: Surgical treatment remains the cornerstone of therapeutic management of head and neck sarcomas.

MMP-3 mRNA and MMP-3 and MMP-1 proteins in bladder cancer: a comparison with clinicopathologic features and survival.

Matrix metalloproteinases (MMPs) are proteolytic enzymes important at several points during multistep neoplastic progression. Although MMP-1 and MMP-3 have been implicated in the progression of various human cancers, their expression in bladder cancer has not been addressed. Immunohistochemistry (Strept-ABC-HRP method) and in situ hybridization were performed to detect MMP-1 protein, MMP-3 protein, and MMP-3 mRNA, respectively, in 59 transitional cell bladder carcinomas. To assess the role of these MMPs in bladder cancer, their expression was evaluated in relation to known clinicopathologic parameters and patients' disease-free and overall survival. Immunoreactivity for MMP-1 and MMP-3 proteins was observed in the cytoplasm of cancer cells in 30.5% and 24% of samples, respectively. Transcripts for MMP-3 mRNA were localized in stromal cells in 71.2% of cases and in cancer cells in 49% of cases. MMP-1 immunoreactivity demonstrated a statistically significant association with deeply invasive and grade III tumors versus superficial and lower grade tumors. MMP-3 protein immunoreactivity and MMP-3 mRNA immunolocalization did not associate with the parameters studied. However, MMP-3 mRNA localization in stromal cells demonstrated a borderline association with poor patients' disease-free and overall survival. In conclusion, the authors' results demonstrate a differential expression between MMP-1 and MMP-3 in bladder cancer; MMP-1 appears to participate in invasiveness and possibly in loss of differentiation in urothelial carcinomas in contrast to MMP-3.

Expression patterns of beta-catenin in in situ and invasive breast cancer.

BACKGROUND: beta-Catenin plays a central role in the E-cadherin/catenin cell-cell adhesion complex and is possibly involved in cellular signalling pathways. In this study, we evaluated the expression patterns of this molecule in in situ and invasive breast cancer. METHODS: The expression of beta-catenin was evaluated in 121 breast cancer specimens by immunohistochemistry. Its relationship to clinicopathological features was also investigated. RESULTS: Altered beta-catenin expression was found in 68% of tumours. Lobular carcinomas showed abnormal beta-catenin expression more frequently (77%) than ductal carcinomas (64%) with 46% of lobular cases showing complete absence of beta-catenin immunoreactivity. Cytoplasmic beta-catenin localization was seen only in ductal carcinomas. Aberrant beta-catenin expression was observed in 54% of ductal carcinomas in situ with highly concordant beta-catenin expression patterns in the nearby in situ and invasive components. CONCLUSIONS: Quantitative and qualitative changes in beta-catenin expression occur in a considerable proportion of in situ and invasive ductal carcinomas and are more prominent in invasive lobular carcinomas.

c-met tyrosine kinase receptor expression is associated with abnormal beta-catenin expression and favourable prognostic factors in invasive breast carcinoma.

AIMS: Receptor-type tyrosine kinases are important in cell signal transduction and proliferation. Abnormal expression of tyrosine kinases often leads to malignant transformation. c-met is a tyrosine kinase receptor and its ligand is hepatocyte growth factor (HGF). In this study, we have evaluated c-met expression in 69 invasive breast carcinomas and statistically analysed this expression with known clinicopathological prognostic parameters and patients' survival. We also studied for the first time c-met expression in association with E-cadherin and beta-catenin expression. METHODS AND RESULTS: Immunohistochemistry (ABC-HRP method) was peformed for the detection of c-met, E-cadherin and beta-catenin. c-met immunoreactivity was observed in 58% of cases and was associated with the lobular type of breast carcinomas (P = 0.012), low histological grade ductal carcinomas (P = 0.05), favourable prognostic and predictive factors such as oestrogen and progesterone receptor immunohistochemical expression and negative c-erbB-2 expression (P = 0.05, P = 0.014 and P = 0.03, respectively). c-met immunoreactivity did not correlate with lymph node status, tumour size and stage of the disease. Cox's proportional hazard regression model demonstrated that tumours with positive c-met immunoreactivity correlated significantly with favourable patients' survival (P = 0.028). When c-met staining was compared with E-cadherin and beta-catenin expression, a statistical significant correlation was established between c-met immunoreactivity and abnormal beta-catenin expression (P = 0.025) suggesting possible involvement of c-met in the downregulation of the E-cadherin-catenin complex, possibly through tyrosine phosphorylation of beta-catenin. CONCLUSION: c-met immunohistochemical expression seems to be associated with abnormal beta-catenin expression, good prognostic and predictive factors and favourable outcome in breast cancer patients.

Tissue immunodetection of c100 hepatitis C virus antigen in major thalassemic patients.

BACKGROUND/AIMS: Hepatitis C Virus (HCV) detection in the livers of chronically infected patients remains a debatable issue. To determine the significance of hepatic expression of hepatitis C viral antigen c100, an immunohistochemical assay was performed in 113 young thalassemics with chronic HCV infection. METHODOLOGY: One hundred and thirteen patients were seropositive for antibody to HCV by second-generation testing. The monoclonal antibody TORDJI-22 was used in an alkaline phosphatase 3-step staining method, and any possible association between the results of HCV immunodetection and various clinicopathologic variables was investigated by univariate and multivariate statistical analysis. In 36 cases, post-therapy liver biopsy specimens were also studied. RESULTS: HCV c100 antigen was detected in 62% of all pretherapy samples, exclusively in the cytoplasm of rather few hepatocytes. Its expression was positively associated with male gender (p = 0.02) as well as with rather advanced age (p = 0.03) and was frequently accompanied by low necroinflammatory scores (according to the modified HAI grading). At the end of interferon-alpha (IFN-alpha) therapy, the immunoreactive prevalence of c100 antigen decreased significantly (pF = 0.002). CONCLUSIONS: We conclude that hepatic expression of c100 antigen is detected in a considerable percentage of thalassemics but it is not likely to provide information concerning the viral load in the infected liver. IFN therapy appears to reduce the hepatic expression of this viral antigen in thalassemic patients.