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R Buffa

Publications and source records attributed to R Buffa.

At least 37 records · Page 2Linked to original sources
PubMed1997

p53 protein accumulation and p53 gene mutation in esophageal carcinoma. A molecular and immunohistochemical study with clinicopathologic correlations.

BACKGROUND: p53 gene mutation and p53 protein accumulation are common in human cancer. However, their clinical significance is controversial and p53 accumulation may not correlate with gene mutation. The current study investigates the occurrence of p53 alterations in esophageal carcinoma, the correlation between the analyses at the gene and protein level, and their prognostic significance. METHODS: A series of 74 esophageal carcinomas (46 squamous cell carcinomas, 21 Barrett's adenocarcinomas, and 7 undifferentiated carcinomas) was studied by single strand conformation polymorphism (SSCP) analysis and immunohistochemistry (IHC) to detect p53 mutation and accumulation, respectively. RESULTS: p53 mutations in exons 5-8 were detected in 53% of the carcinomas whereas p53 accumulation was observed in 57% of cases. Comparing SSCP and IHC, there were 27 discordant cases (38%). Overall, only 20 tumors (27%) did not display p53 mutation and/or p53 accumulation. No associations were found between p53 aberrations and clinicopathologic parameters, including patients age and gender tumor type, stage, and grade. p53 protein accumulation and p53 gene mutation were not related to patient survival by univariate or multivariate analysis in esophageal carcinomas. CONCLUSIONS: p53 aberrations are very common in esophageal carcinomas. However, p53 gene mutation and p53 protein accumulation have a significant discordance, suggesting that p53 function may be inactivated by mechanisms other than mutation. p53 aberrations do not independently predict prognosis in esophageal tumors.

Adenocarcinoma↗
PubMed1997

Granulomatous sarcoidotic lesion of hypothalamic-pituitary region associated with Rathke's cleft cyst.

The association of large pituitary mass, lack of clinical syndromes of pituitary hypersecretion, hypopituitarism and visual field defects suggests the diagnosis of nonfunctioning pituitary adenoma, but the same characteristics can be present in patients affected by other tumorous lesions, cysts, inflammatory processes or vascular disease. The management of these patients depends on a correct diagnosis. A 53-year-old woman was admitted for nausea, vomiting and severe hypotension. For three months she had complained of weakness, sleepness, skin-dryness and loss of weight. Imaging and endocrine evaluations revealed an intra and extrasellar mass causing hypopituitarism without diabetes insipidus. Histological examination of the tissue obtained at transsphenoidal surgery showed a Rathke's cleft cyst, surrounded by areas of noncaseous granulomatous tissue with scattered multinucleated giant cells of foreign body type, similar to a sarcoid lesion. Other systemic sarcoidosis localizations were absent. After two years of full well-being, the patient reported a sudden visual impairment, due to sarcoidosis involvment of the prechiasmatic tract of the optic nerve, that promptly improved with corticosteroid treatment. This report emphasizes the overlap of signs and symptoms between non functioning tumors and nontumoral masses of hypothalamic-pituitary region and underlines the fact that a correct diagnosis is feasible only on histopathological basis. Although, occasionally, the coexistence of Rathke'cyst with pituitary adenoma has been reported, to the best of our knowledge, this is the first report of the association between Rathke's cleft cyst and noncaseating granuloma tissue. Finally, the remission of neurolgical symptoms following corticosteroid therapy confirms this treatment as a valid medical approach and suggests its use in a short therapeutic trial when the diagnosis is doubtful.

Cysts↗
PubMed1997

Polysialylated N-CAM, chromogranin A and B, and secretogranin II in neuroendocrine tumours of the lung.

Highly alpha 2-8-sialylated N-CAM (neural cell adhesion molecule) impairs N-CAM-mediated cell adhesion. We investigated polysiaN-CAM immunoreactivity in a range of neuroendocrine lung tumours: 15 typical carcinoids, 21 atypical carcinoids, 2 large cell neuroendocrine carcinomas and 12 small cell lung carcinomas were selected on a morphological basis and by their immunoreactivity for chromogranin A and B and secretogranin II. A progressive loss of chromogranin expression, particularly of chromogranin B, was paralleled by the up-regulation of polysiaN-CAM in histologically more aggressive tumours (P = 0.001). These data support the hypothesis that loss of cell-cell adhesion properties might be a relevant factor in the origin of the aggressivity of lung neuroendocrine tumours.

Antibodies, Monoclonal↗
PubMed1997

Cyclin D1 protein expression is related to clinical progression in laryngeal squamous cell carcinomas.

The expression of cyclin D1 gene was investigated in 74 laryngeal squamous cell carcinomas (LSCCs) in order to determine its clinical and prognostic value. Overexpression of cyclin D1 was detected immunohistochemically using DCS6 monoclonal antibody on formalin-fixed, paraffin-embedded tissue sections. Cyclin D1 expression was detected in 22 of the 74 cases investigated (30 per cent), thirteen of which presented nodal metastases (59 per cent); of the patients without any detectable cyclin D1 protein expression, six presented nodal metastases (12 per cent). Cyclin D1 protein expression was found in five per cent of the specimens of normal mucosa, eight per cent of those with low-grade dysplasia and 20 per cent of those with high-grade dysplasia. A statistically significant association was found between cyclin D1 expression and the supraglottic site (p < 0.05), tumour extension (p < 0.001), the presence of lymph node metastases (p < 0.001), and advanced clinical stage (p < 0.001). Cyclin D1 expression analysis is an important tool in the selection of LSCC patients with an aggressive clinical course.

Aged↗
PubMed1997

Expression of the epidermal growth factor receptor gene in human intestinal metaplasia: a preliminary report.

BACKGROUND: The role of growth factors/receptors in the etiopathology and/or development of gastric cancer has recently come under scrutiny, since overexpression or amplification of the EGF system has been found in many intestinal type gastric cancers and related to a more aggressive behavior. Since these gastric carcinomas appear to develop from intestinal metaplasia, a study was planned to investigate whether overexpression of the EGF-receptor gene also occurred in intestinal metaplastic mucosa. METHODS: Patients underwent upper GL endoscopy. Gastric biopsies for routine histology, Helicobacter pylori detection, quantification of intestinal metaplasia and EGF-R expression analysis were performed. A 30mer EGF-R specific oligonucleotide was end-labeled and used to probe a dot blot filter containing the RNA from the bioptic samples. RESULTS: Though all the gastric samples transcribed the EGF-R gene to a detectable level, overexpression of the EGF-R gene was found in the metaplastic mucosa in a minority of patients. CONCLUSIONS: These preliminary findings suggest that overexpression of the EGF-R gene is infrequent in the metaplastic gastric mucosa.

Aged↗
PubMed1997

MDM-2 oncoprotein overexpression in laryngeal squamous cell carcinoma: association with wild-type p53 accumulation.

The MDM-2 gene encodes for a nuclear phosphoprotein that binds p53 and inhibits its ability to activate transcription by concealing the p53 activation domain. It has been suggested that MDM-2 overexpression might represent an alternative mechanism by which p53-mediated pathways are inactivated in human tumors. MDM-2 overexpression can be detected by immunohistochemical analysis as a result of gene amplification and/or increased mRNA expression. We studied MDM-2 gene amplification and protein overexpression in 46 and 50 cases, respectively, of laryngeal squamous cell carcinomas previously analyzed for p53 gene alterations. Not one of the cases showed MDM-2 gene amplification, whereas MDM-2 nuclear immunoreactivity was found in 17 tumors (34%). In 10 of these, coexpression of p53 protein was detectable in the absence of gene mutations in exons 5 through 9 (P = .03). Likewise, MDM-2 was also overexpressed in 18 (46%) of 39 morphologically normal mucosa samples, 15 (50%) of 30 preneoplastic lesions, and 9 (40%) of 22 cases of severe dysplasia. Finally, we found no significant correlations between MDM-2 expression (neither per se nor in association with wild-type or mutated p53), and the evaluated clinicopathologic parameters of histologic grade, lymph node status, or clinical stage. Our results suggest that MDM-2 gene amplification might not occur in laryngeal carcinomas and that MDM-2 protein overexpression might represent an alternative mechanism by which p53 is inactivated in the early stages of laryngeal cancer tumorigenesis.

Adult↗
PubMed1996

Ontogeny, distribution and amine/peptide content of chromogranin A- and B-immunoreactive endocrine cells in the small and large intestine of the chicken.

Chromogranin A-(CgA-) and chromogranin B-(CgB-)-immunoreactive endocrine cells were investigated in the chicken intestine during embryonic and post-hatching life. CgA- and CgB-immunoreactive cells first appeared in the intestinal tract at various embryonic ages from day 10 in the cloaca to day 16 in the distal ileum and colon. To identify the CgA- and CgB-immunoreactive cells, each tissue section was double-immunostained using a panel of polyclonal antibodies raised against gut amine/peptides. Almost all the serotonin-immunoreactive cells co-localised CgA and CgB along the entire intestinal mucosa and at all ages examined. In contrast, substance P-, peptide tyrosine tyrosine-, neurotensin- and secretin-immunoreactive cells displayed heterogeneous co-localisation patterns. For example, either all or only some cells of a given endocrine type co-stored Cg; they did so variously - only in the embryo, only after hatching, or at both stages, and co-localizing cells were sometimes located within the mucosa only in the villi and not in the glands, and sometimes vice versa. All the CgA/CgB-immunoreactive cells also displayed argyrophilia.

APUD Cells↗
PubMed1996

p53 protein expression in laryngeal squamous cell carcinomas bearing wild-type and mutated p53 gene.

We performed an immunohistochemical analysis to investigate the expression of p53 protein in a panel of 18 laryngeal squamous cell carcinomas, 15 primary tumours and three in relapse, previously analysed by us for the presence of p53 gene mutations. Dysplastic and/or normal surrounding mucosa was evaluated in 15 different tumours. The results of our study are the following: (1) expression of p53 protein was observed in one out of five tumours positive for p53 gene mutations (20%) and in 10 out of 13 (80%) negative cases; (2), p53 protein over-expression was frequently observed in normal and/or dysplastic mucosa surrounding either wild-type (7/11) or mutated p53 tumours (2/4); (3), p53 immunoreactive cells showed a pattern of distribution in normal and mildly/ moderately dysplastic mucosa (basal layers), different from that in severely dysplastic mucosa (whole thickness). These data further support the hypothesis that p53 protein over-expression may be a marker of the earliest phases of multistep tumorigenesis in laryngeal squamous cell carcinoma.

Aged↗
PubMed1996

Three-step immunoscintigraphy with anti-chromogranin A monoclonal antibody in tumours of the pituitary region.

In the present paper we evaluated the ability of pretargeted immunoscintigraphy (ISG) with antichromogranin A (CgA) monoclonal antibody (Mc-ab A11) in visualizing pituitary masses. The results obtained in 23 patients are described along with those of [111In]pentetreotide scintigraphy (Octreoscan) in 18 cases. Positive ISG was obtained in 9/11 (82%) non-functioning, 1/4 growth hormone-, 1/2 prolactin-, 1/2 thyrotropin-, 1/1 follicle-stimulating hormone-, 0/1 adrenocortico-trophin-secreting pituitary adenomas. In one patient with a positive ISG scan of a non-functioning pituitary adenoma, an associated neurinoma of the acoustic nerve was not imaged. The same occurred in one patient with a pituitary deposit from a mammary carcinoma and in another one with a cyst of the Rathke's pouch. Chromogranin A immunohistochemistry, carried out in 10 tumours, was positive in eight pituitary adenomas and negative in two non-adenomatous lesions. A concordant ISG occurred in all cases except for two pituitary adenomas: one cystic and necrotized and one post-operative remnant very small in size. In 18 patients with pituitary adenoma both ISG and Octreoscan were positive in 61% of cases but with a different distribution among tumours. At variance with ISG, Octreoscan visualized only 5/10 (50%) non-functioning pituitary adenomas and all (4/4) somatotropinomas. In conclusion, ISG is able to image pituitary tumours and particularly non-functioning pituitary adenomas. In this respect, it may be helpful in discriminating non-neuroendocrine masses of the pituitary region from non-functioning pituitary adenomas.

Adolescent↗
PubMed1995

Ontogeny, distribution and amine/peptide colocalization of chromogranin A- and B-immunoreactive cells in the chicken gizzard and antrum.

The ontogeny and the distribution of chromogranin A (CgA)- and chromogranin B (CgB)-immunoreactive endocrine cells was studied in the chicken gizzard and gizzard-duodenal junction (also called pylorus or antrum) during embryonic and postnatal life. The same tissue sections were then double-immunostained to identify the CgA-and CgB-immunoreactive cells, with a panel of polyclonal antibodies raised against main gut amine/peptides. In the gizzard, positive cells were observed only in its two diverticula (proximal and distal caeca), where the first CgA- and CgB-immunoreactive cells were found on day 12 of incubation. They always remained moderate in number and co-stored mainly serotonin, gastrin/CCK and neurotensin. A few also co-stored somatostatin, but only during the embryonic period. Others co-stored PYY, but only after hatching. Co-localization with motilin was rare and never occurred with bombesin. In the chicken antrum, the first CgA- and CgB-immunoreactive cells were observed on day 12 of incubation and soon reached very high numbers. Antral positive cells showed almost the same co-localization pattern as the gizzard diverticula. Despite their high chromogranin content, the antral cells had weak argyrophilia, whereas in the gizzard diverticula the two staining patterns corresponded.

Amines↗
PubMed1995

The prevalence and clinical significance of chromogranin A and secretogranin II immunoreactivity in colorectal adenocarcinomas.

Colorectal adenocarcinomas may display features of endocrine differentiation, shown by argyrophil stains and by the expression of endocrine markers such as chromogranin A. We investigated chromogranin A and secretogranin II immunoreactivity in a series of 208 carcinomas of the large bowel to assess the prevalence and clinical significance of endocrine differentiation. Tumors expressing endocrine markers were classified as low expressors (< than 1 immunoreactive tumour cell/mm2) and high expressors (> than 1 immunoreactive tumour cell/mm2). There were 33 (16%) carcinomas showing both chromogranin A and secretogranin II immunoreactivity: 11 tumours (5%) were high expressors. Endocrine differentiation was not related to the disease stage, tumour location, grade, DNA ploidy and p53 protein accumulation. In the entire series chromogranin A immunoreactivity did not provide prognostic information using univariate and multivariate analysis. A worse overall survival (P = 0.048) was demonstrated for the stage III patients with high expressor tumours, but there were only five patients in this group. The results of our investigation suggest that chromogranin A immunoreactivity is not a useful variable in the prognostic assessment of colorectal adenocarcinomas.

Adenocarcinoma↗
PubMed1994

Immunohistochemical localization of chromogranin A and B in the endocrine cells of the alimentary tract of the green frog, Rana esculenta.

Novel monoclonal antibodies to human chromogranin A (CgA) and chromogranin B (CgB) were used to investigate the presence of immunoreactive (-IR) elements in the alimentary tract of the green frog Rana esculenta. Numerous CgA-IR and a few CgB-IR endocrine cells were found within the gut mucosa, from the oesophagus to the cloaca, with some local differences in density. Co-localization studies demonstrated that they were co-stored in almost all the serotonin-IR, the amylin-IR or islet amyloid polypeptide-IR cells and in the peptide tyrosine tyrosine-IR cells located proximal to the pylorus, but not in those located in more caudal tracts. No other co-localization was demonstrated; substances investigated included somatostatin, substance P, gastrin/cholecystokinin, glucagon, glycentin, bombesin, secretin and neurotensin. CgA-IR and CgB-IR cells nearly always displayed argyrophilia with the Grimelius silver method.

Amyloid↗
PubMed1994

Production of basic fibroblast growth factor by gastric carcinoid tumors and their putative cells of origin.

Using immunohistochemical techniques a subpopulation of endocrine cells in the human oxyntic mucosa was found to react with antibodies against basic fibroblast growth factor (bFGF). These cells were identified as histamine-producing enterochromaffin-like (ECL) cells and, to a minor extent, serotonin-producing enterochromaffin cells. Basic fibroblast growth factor immunoreactive cells were most frequently found in hyperplastic lesions of ECL cells occurring in hypergastrinemic patients (20 of 27 cases) and in ECL cell carcinoid tumors (10 of 17 cases). In addition, bFGF mRNA was demonstrated by Northern blot analysis of homogenates from two gastric carcinoids cytologically characterized as pure ECL cell tumors. Although the function of bFGF in normal cells remains unknown, its production in neoplastic conditions may be responsible for the associated desmoplastic and angioblastic proliferations. Moreover, secretion of bFGF by hyperplastic or neoplastic ECL cells may contribute to the circulating levels of the bFGF-like mitogenic factor identified in patients affected by multiple endocrine neoplasia type 1 syndrome.

Carcinoid Tumor↗
PubMed1994

Phylogenetic aspects of the occurrence and distribution of secretogranin II immunoreactivity in lower vertebrate gut.

A novel monoclonal antibody raised against bovine secretogranin II (Sg II) was used in immunohistochemical studies on amphibian (Rana esculenta), reptilian (Podarcis sicula) and avian (Gallus gallus) gut. Sg II immunoreactivity was detected in epithelial and nervous elements. Cells immunoreactive for Sg II were examined by double immunostainings to determine whether they might also co-store certain previously known bioactive amine/peptide substances. Almost all the endocrine cells immunoreactive for bombesin, substance P, neurotensin, gastrin/cholecystokinin, neuropeptide tyrosine (NPY) and calcitonin gene-related peptide as well as some of those immunostained for serotonin, histamine, and polypeptide tyrosine tyrosine (PYY) also contained Sg II. Sg II-immunoreactive cells varied in number and distribution according to regions of the gut and animal species. The number of Sg II immunoreactive granules notably varied not only according to cell type, but also within the same cell population. Many histamine-, calcitonin gene-related peptide (CGRP)-, substance P-, PYY-, and neurotensin-immunoreactive neurons also contained Sg II. These were mostly situated in the myenteric plexus; their distribution pattern varied among the three species. These findings show that, despite being well conserved during phylogeny, Sg II has a heterogeneous distribution.

Animals↗