Biomedical subjects

Walter F Grigioni

Publications and source records attributed to Walter F Grigioni.

8 recordsLinked to original sources

PubMed2004

Endothelial cell differentiation in hepatocellular adenomas: implications for histopathological diagnosis.

BACKGROUND/AIMS: Little information is available about the patterns of endothelial cell differentiation observed in hepatocellular adenomas. We therefore aimed to analyze the endothelial cell immunophenotype in a large series of these tumors and evaluate its possible diagnostic relevance. METHODS: The expression of continuous and sinusoidal endothelial cell markers and of extracellular matrix proteins was analyzed by immunoperoxidase in 56 adenomas, as compared with 30 cases of focal nodular hyperplasia (FNH), 2 cases of telangiectatic FNH and 40 cases of hepatocellular carcinoma (HCC). RESULTS: Twenty-eight adenomas (50%) presented a sinusoidal pattern of endothelial cell differentiation, characterized by the expression of specific sinusoidal endothelial cell markers and the presence of a subendothelial matrix resembling the normal perisinusoidal matrix. Eleven tumors (19.5%) presented a continuous pattern of endothelial cell differentiation. Seventeen tumors (30.5%) showed a mixed pattern. Twenty-eight FNH presented a sinusoidal pattern of endothelial cell differentiation; all HCC presented a continuous pattern of endothelial cell differentiation. CONCLUSIONS: In hepatocellular adenomas, intra-tumoral vessels usually present a sinusoidal pattern of endothelial cell differentiation. However, the vascular phenotypic heterogeneity observed in our study questions the potential relevance of endothelial cell immunophenotyping for the differential diagnosis between hepatocellular adenomas and well differentiated HCC.

Adenoma, Liver Cell↗

PubMed2003

A multiorgan donor cancer screening protocol: the Italian Emilia-Romagna region experience.

BACKGROUND: We describe the Emilia-Romagna screening protocol for all multiorgan donors within this region of Italy and report on the first 2 years of implementation. SETTING: Setting is a 24-hour multidisciplinary call service covering the 16 intensive care units in Emilia-Romagna (3,969,000 inhabitants) and a centralised pathology center, directed by a transplant coordination center. STUDY POPULATION AND PERIOD: All 271 effective donor candidates presenting in Emilia-Romagna in 2001-2002. PROTOCOL: Anamnesis, external examination, and thorough laboratory and instrumental screening is followed by sampling of internal effusions and evaluation of all internal organs. All suspect findings are then investigated by extemporary pathologic evaluation. To fit national legal requirements, candidates are classified as standard risk (no transmissible risk); nonstandard risk (low-risk of transmission, eligibility restricted to certified clinical emergencies pending informed consent); and unacceptable risk (unconditional exclusion because of high-risk pathologies). RESULTS: The protocol was successfully implemented for all 271 candidates. In addition to 14 independent exclusions, clinical suspicion of cancer was raised for 61 donors presenting with 82 lesions or effusions. Along with one case of lymph-node tuberculosis (unacceptable risk), histocytologic screening revealed eight cases of malignancy (5 prostate, 1 papillary-thyroid, 1 follicular-thyroid, and 1 renal cell, all nonstandard risk); the remainder were benign (standard risk). Protocol implementation led to exclusion of 8 (3.0%) candidates (1 nonstandard risk transplantation was performed). CONCLUSIONS: This stringent protocol-now adopted with some modifications at a national level-provides an initial example of a feasible intervention aimed at maximising donation safety while rationalizing use of marginal donors.

Adolescent↗

PubMed2003

Expression of beta-galactoside alpha2,6 sialyltransferase and of alpha2,6-sialylated glycoconjugates in normal human liver, hepatocarcinoma, and cirrhosis.

beta-Galactoside alpha2,6-sialyltransferase (ST6Gal.I) mediates the addition of alpha2,6-linked sialic acid to glycoproteins. ST6Gal.I is strongly expressed by the liver and is up-regulated in several cancers, but little is known of its regulation in human liver diseases. We have investigated the expression of ST6Gal.I and its product, the alpha2,6-sialylated lactosamine, in normal human liver, hepatocarcinoma (HCC), and cirrhosis. We found that both ST6Gal.I activity and mRNA can undergo up- or down-regulation in different HCC patients. At the mRNA level, the groups of specimens showing the highest expression were HCC of grade 2, HCC developed without preexisting cirrhosis, and HCC of male patients. The lectin from Sambucus nigra (SNA) reveals a significative overexpression of alpha2,6-sialylated glycoconjugates in HCC tissue homogenates and their intracellular accumulation in HCC histological sections, even though in a few cases the extent of alpha2,6-sialylation dramatically decreases. Transcription of the gene occurs through at least two different promoters, resulting in two differentially expressed mRNA species. RNA in situ hybridization reveals that the ST6Gal.I mRNA can be expressed at a quantitatively heterogeneous level among the neoplastic cells. Neither ST6Gal.I expression nor alpha2,6-sialylation are altered in cirrhosis. These data indicate that neoplastic transformation but not cirrhosis can alter the process of alpha2,6-sialylation of liver glycoproteins.

Aged↗

PubMed2003

Increased expression of p21 (WAF1/CIP1) cyclin-dependent kinase (CDK) inhibitor gene in chronic allograft nephropathy correlates with the number of acute rejection episodes.

The p21 (WAF1/CIP1) cyclin-dependent kinase (CDK) inhibitor gene is considered to be the senescence marker in some recent publications. Expression of the gene was evaluated in 14 normal human kidney tissues of different ages and in nine chronically rejected renal allografts. All normal kidneys were negative for p21 expression. Glomerular, tubular and interstitial expression of the marker was detected in 88.9% ( P<0.0001) and vascular expression in 66.7% of chronically rejected grafts ( P<0.001). No correlation was found between the intensity of p21 expression and recipient age, donor age or number of human leukocyte antigen (HLA) mismatches. The marker was expressed more in grade 3 of chronic allograft nephropathy (CAN) than in grade 2 ( P=0.059 for glomerular score). Tubular expression of p21 was correlated with the number of acute rejections: P<0.05 for three vs one and two, and P=0.0046 for three vs no previous acute rejection episodes.

Acute Disease↗

PubMed2003

Increased expression of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor genes in aging human kidney and chronic allograft nephropathy.

BACKGROUND: The goal of the current study was to examine the potential value of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor (CDKI) genes in the process of human kidney aging in vivo, and in the development of chronic allograft nephropathy (CAN). METHODS: Expression of p16(INK4a) and p27(Kip1) CDKI genes was evaluated and compared in 20 normal human kidney tissues of different ages (range, 21 to 80 years) and in 9 chronically rejected kidney grafts. Age dependency of marker expression was analyzed by the Pearson correlation and linear regression. RESULTS: Expression of p16 in cortical tubular (CTS) and interstitial (CIS) cells of normal kidney was age dependent (correlation coefficients: 0.608 and 0.726, 95% confidence interval [CI]: 0.227 to 0.828 and 0.417 to 0.884, respectively). Cortical tubular expression of p27 was also correlated with increasing age (0.672, 95% CI: 0.327 to 0.859). Linear regression analyses confirmed the linearity of marker relationship with age (coefficient of determination R(2):0.370, 0.452, and 0.527 for CIS p16, CTS p27, and CTS p16, respectively). The mean chronological and predicted graft ages (53 +/- 21 and 76 +/- 8.9 years, respectively) were significantly different (P = 0.0126). The glomeruli, tubules, and interstitial cells of rejected grafts expressed significantly higher levels of p16 and p27 than normal kidneys. Expression of p16 in glomerular and cortical interstitial cells was higher in grade 3 of CAN than in grade 2 (P = 0.013 and 0.004, respectively). CONCLUSION: The results of the current study show that expression of p16(INK4a) and p27(Kip1) CDKI genes is increased in cortical cells of the aging human kidney and in chronic allograft rejection, supporting the senescence theory of CAN.

Adolescent↗

PubMed2003

Primary diffuse meningeal melanomatosis: radiologic-pathologic correlation.

We report a case of primary diffuse meningeal melanomatosis, a rare variant of primary malignant melanoma of the CNS, in a 68-year-old woman. The disease mimicked intracranial hypotension syndrome and was diagnosed only at autopsy (CSF cytologic results were negative). CT revealed hydrocephalus with effacement of the cerebral convexity sulci and abnormal contrast enhancement in the right sylvian and frontoparietal fissures, whereas MR imaging showed diffuse marked dural and leptomeningeal contrast enhancement. In retrospect, these nonspecific findings correlated with the extensive leptomeningeal invasion in the cerebral hemispheres, brain stem and spinal cord. The clinical, radiologic, and pathologic features of diffuse meningeal melanomatosis are reviewed.

Aged↗

PubMed2002

Expression, regulation, and function of alpha V integrins in hepatocellular carcinoma: an in vivo and in vitro study.

The expression of alpha V integrins by neoplastic cells contributes to the promotion of local invasion and metastasis. The most characteristic extracellular ligands of alpha V integrins are vitronectin and fibronectin. Hepatocytes are the main source of vitronectin, and the capacity to synthesize and secrete vitronectin is usually retained in hepatocellular carcinoma. The aim of this study was to explore the expression, regulation, and functional role of alpha V integrins in hepatocellular carcinoma. We first analyzed the expression of alpha V integrins and their ligands fibronectin and vitronectin in 80 cases of hepatocellular carcinoma. alpha V integrin chain was detected in 44 cases and vitronectin in 50. Twenty-four of the 44 alpha V-positive tumors contained large amounts of vitronectin. These cases presented more frequently with adverse histoprognostic factors, including infiltrative growth pattern (62.5%), lack of capsule (71%), presence of capsular invasion (57%), and satellite nodules (50%). We then used HepG2 and Hep3B cell lines as in vitro models to study alpha V integrin regulation and function. HepG2 and Hep3B cells expressed alpha V integrin chain and used alpha V beta 1 and alpha V beta 5 for adhesion and migration on vitronectin. Tumor necrosis factor (TNF) alpha and transforming growth factor (TGF) beta significantly increased the expression levels of alpha V integrins and stimulated the adhesion and migration of both HepG2 and Hep3B cell lines on vitronectin. The effects of growth factors on cell adhesion and migration were reproduced by incubation with conditioned medium from rat liver myofibroblasts. In conclusion, our results support the existence of an alpha V integrin/vitronectin connection in hepatocellular carcinoma and suggest that this connection may be an adverse prognostic factor.

Adult↗

PubMed2002

Primary paraganglioma strictly confined to the liver and mimicking hepatocellular carcinoma: an immunohistochemical and in situ hybridization study.

We describe a case of primary nonfunctioning paraganglioma that, unlike any other previously reported case, was strictly confined to the liver and must therefore have arisen on liver parenchyma. An asymptomatic 46-year-old man was referred to us for laparotomy and a right hemihepatectomy after a preoperative diagnosis of fibrolamellar hepatocellular carcinoma, based on a fine-needle biopsy. An 8-cm resiliently firm, pale gray nodule with a large central area of fibrosis and a thin fibrous capsule was resected. The polygonal eosinophilic tumor cells containing round nuclei lacking nucleoli were arranged in small nests set in a vascularly rich stroma. At immunohistochemistry neoplastic cells were strongly positive for chromogranin A, neuron-specific enolase, synaptophysin, and IGF-II protein; they were negative for keratin, S-100 protein, CD10, vimentin, and smooth muscle actin. In situ hybridization confirmed that, as in other sites, liver paraganglioma can express IGF-II gene. Conversely (and unlike hepatocellular carcinomas), the neoplastic cells did not express albumin mRNA, which was detected only in surrounding hepatocytes. The clinical course was benign and the patient is well and free of neoplastic disease 9 years after surgery. Knowledge of the entity should avoid possible confusion with hepatocellular carcinoma, especially of the fibrolamellar variety.

Carcinoma, Hepatocellular↗