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R Buffa

Publications and source records attributed to R Buffa.

At least 19 recordsLinked to original sources

A primary adrenal non-Hodgkin's lymphoma presenting as an incidental adrenal mass.

The primary adrenal localization of a non-Hodgkin's lymphoma (NHL) is a rare event. We report the case of a 70-yr-old woman, who was admitted at our Institute for a hormonal evaluation after the incidental discovery of a right adrenal mass during ultrasonography (US) performed for cardiovascular disease. At the physical examination, no sign of adrenal hyperfunction was present. She showed only an androgenetic alopecia and her blood pressure was 180/70 mm Hg, with an arrhythmic heart rate of 100 beats/min. No alterations in hormonal and biochemical data were observed. US studies showed a right adrenal mass (major diameter 16 mm), and an abdominal computed tomography (CT) scan confirmed this solid lesion (major diameter 15 mm) with a high density. [75Se] methylnorcholesterol adrenal scintigraphy exhibited a normal symmetrical radiotracer uptake. After 8 months of follow-up, an abdominal CT scan demonstrated a significant increase of the right adrenal mass (major diameter: 40 mm), with a solid tissue density and enhancement after i.v. contrast. [75Se] methylnorcholesterol adrenal scintigraphy showed an absent uptake on the right side versus the contralateral side. The hematological, hormonal and radiological evaluation did not reveal any sign of malignancy. Owing to the mass enlargement and the modification of scintigraphic pattern, the patient underwent unilateral adrenalectomy. Histological examination revealed a primary diffuse large B-cell NHL (REAL classification) of the adrenal gland. After surgery, she underwent a combined polychemotherapy (cyclophospamide, adriamycin, vincristine and prednisone) and subsequently one cycle of radiotherapy. At present, the patient is in good conditions and there are no signs or symptoms of recurrent disease.

Adrenal Gland Neoplasms↗

Clinical relevance of microvessel density in laryngeal squamous cell carcinomas.

The clinical implications of microvessel density (MVD) in head and neck tumors have not been fully elucidated. We investigated the clinicopathologic correlates and prognostic relevance of MVD in a series of 122 consecutive patients with surgically treated laryngeal squamous cell carcinoma followed-up for a mean of 79 months. MVD was evaluated after CD34 immunostaining in 3 250x microscopic fields representative of the "hot spot" area, and expressed as the mean value of the vessel counts per millimeter squared. The overall median value of the intratumoral vessel count was 69.5/mm(2). In the 20 cases we analyzed, MVD increased significantly from normal to dysplastic mucosa and infiltrating carcinoma (p = 0.0001). Nineteen carcinomas (15.6%) had MVD values that were equal to or lower than the highest MVD value (52.7/mm(2)) observed in normal mucosa samples (in which the median MVD count was 34.5/mm(2), range 16.6-52.7/mm(2), mean 35.1 +/- 11.5/mm(2)) and were therefore considered poorly vascularized. Periodic acid-Schiff (PAS) staining revealed intratumoral PAS-positive connective tissue septa in 13 cases (10.7%). The patients with poorly vascularized tumors showed a tendency toward a better prognosis, but the anatomical site, tumor extension and clinical stage were the only variables significantly associated with disease-free and overall survival.

Adult↗

Immunoreactivity for p27(KIP1) and cyclin E is an independent predictor of survival in primary gastric non-Hodgkin's lymphoma.

Our aim was to assess the prognostic implications of the expression of p27(KIP1) and cyclin E in gastric lymphoma. We investigated the prognostic value of the immunoreactivity of these molecules in 92 cases of primary gastric lymphoma: 34 LGMLs, 24 DLCLMLs and 34 DLCLs. p27 was positive in 88% of LGMLs, 71% of DLCLMLs and 32% of DLCLs (p = 0.004); cyclin E was positive in 9%, 33% and 59% of cases, respectively (p < 0.00001). p27/cyclin E immunoreactivity significantly correlated with histologic category, stage and LDH serum level. p27 immunoreactivity was significantly associated with better survival, whereas cyclin E reactivity was significantly related to worse outcome. Five-year CSS was 94% for patients with p27(+)/cyclin E(-) phenotype (n = 42), 79% for p27(+)/cyclin E(+) (n = 14) or p27(-)/cyclin E(-) (n = 16) phenotype and 60% for p27(-)/cyclin E(+) phenotype (n = 16) (p = 0.02). The prognostic role of p27/cyclin E expression was confirmed when analyzed separately within LGMLs and large-cell lymphomas. Immunoreactivity for p27 and cyclin E is an independent predictor of survival in PGLs that may be an adjunctive tool in identifying high-risk patients. It correlates with histologic category, stage and LDH serum level. p27(-)/cyclin E(+) phenotype is associated with worse survival, probably due to a synergistic effect of both cell-cycle defects. The predictive role of these molecules within each histologic group of PGLs deserves to be confirmed in larger series.

Adolescent↗

Gastric endocrine cells: types, function and growth.

The history of gastric endocrine cells identification and functional characterization is briefly outlined. An up to date classification of such cells is given. Present status of histopathological, histochemical, ultrastructural and molecular investigations on gastric endocrine hyperplasia and neoplasia is summarized and briefly discussed.

Animals↗

Immunohistochemical analysis of cyclin D1 shows deregulated expression in multiple myeloma with the t(11;14).

The t(11;14)(q13;q32) chromosomal translocation, the hallmark of mantle cell lymphoma (MCL), is recurrently found in multiple myelomas (MM) by means of conventional cytogenetics. Unlike MCL, recent molecular studies of MM-derived cell lines with t(11;14) have indicated that the breakpoints are highly dispersed over the 11q13 region; however, the fact that cyclin D1 is generally overexpressed in these cell lines suggests that this gene is the target of the translocation. To evaluate further the involvement of cyclin D1 in MM, we used immunohistochemistry and fluorescence in situ hybridization to investigate cyclin D1 expression and the presence of chromosome 11 abnormalities in a representative panel of 48 MM patients (40 at diagnosis and 8 at relapse). Cyclin D1 overexpression occurred in 12/48 (25%) of cases; combined immunohistochemistry and fluorescence in situ hybridization analyses in 39 patients showed cyclin D1 positivity in all of the cases (7/7) bearing the t(11;14), in two of the 13 cases with trisomy 11, and in one of the 19 cases with no apparent abnormalities of chromosome 11. Our data indicate that the t(11;14) translocation in MM leads to cyclin D1 overexpression and that immunohistochemical analysis may represent a reliable means of identifying this lesion in MM.

Adult↗

Melanoma antigen genes 1 and 2 are differentially expressed in human gastric and cardial carcinomas.

BACKGROUND: MAGE genes encode for tumor-rejection antigens and are expressed in tumors of different histologic types but not in normal tissues, with the exception of testis and placenta. The aim of this study was to evaluate the frequency of MAGE-1 and -2 expression in gastric and in cardial carcinomas; these conditions have been described as two distinct diseases, having different etiologies, epidemiologic patterns, and gene mutations. METHODS: Two groups of patients were studied: patients with distal gastric carcinoma and patients with carcinoma of the cardia. A group of patients with intestinal metaplasia in the gastric mucosa and controls were also included. All of them underwent upper GI endoscopy. Paired biopsy specimens were taken for routine histology and for RNA extraction, to study the expression of MAGE-1 and -2 genes. RESULTS: None of the intestinal metaplastic samples or controls expressed MAGE-1 and -2 at detectable levels. Whereas 40% of the gastric cancer patients expressed either MAGE-1 or -2, 26.6% transcribed both. In the cardial cancer group, 20% of the cases expressed at least one MAGE, and only 6.6% expressed both genes. These results might reinforce the concept that cancer of the cardia is a distinct neoplastic disease with regard to esophageal and gastric (distal) carcinomas. CONCLUSIONS: Here we show that MAGE gene expression occurs in advanced stages of gastric and cardial cancer and therefore appears to be a late event. This might point to a reconsideration of their potential role in cancer immunotherapy.

Adult↗

Angiogenesis in myelodysplastic syndromes.

It is now well established that solid tumour growth depends on angiogenesis. However, less is known about the generation of new vessels in haematological malignancies and, in particular, in preleukaemic-myelodysplastic syndromes (MDS). In this study, bone marrow microvessel density (MVD) was assessed by immunohistochemistry and compared in trephine biopsies from 14 controls, five infectious disease (ID), 82 MDS, 15 acute myeloid leukaemia (AML) and 14 myeloproliferative disorder (MPD) patients. Statistical analysis (P < 0.001) demonstrated that MDS MVD was higher than in controls and ID (21 +/- 9 vs 6 +/- 2 and 10 +/- 8 respectively) but lower than AML (30 +/- 12) and MPD (40 +/- 12). Among MDS-FAB subtypes, MVD was significantly higher in RAEB-t, CMML and fibrosis subsets compared to RA, RARS and RAEB subsets (P= 0.008). To further investigate angiogenesis machinery, the expression of vascular endothelial growth factor (VEGF) was evaluated by means of immunohistochemistry in control, MDS, AML and MPD biopsies. Even though VEGF mRNA expression was reported in the past in AML cell cultures and cell lines, in our samples VEGF expression was found to be particularly strong in most of the megakaryocytes but significantly less prominent in other cell populations including blasts. Since our findings suggest a correlation between angiogenesis and progression to leukaemia, additional work is now warranted to determine what regulates the generation of new vessels in MDS and leukaemia.

Antigens, CD34↗

Loss of interstitial cells and a fibromuscular layer on the luminal side of the colonic circular muscle presenting as megacolon in an adult patient.

BACKGROUND: Animal studies have shown that the neuromuscular structures on the luminal side of the colonic circular muscle coordinate circular muscle activity. These structures have been identified by electron microscopy in the normal human colon, but have never been thoroughly studied in patients with acquired intestinal hypoganglionosis. AIMS: To perform histological, immunocytochemical, and electron microscopic examinations of the colon of a patient with acquired intestinal hypoganglionosis presenting as megacolon. PATIENT: A 32 year old man with a one year history of constipation and abdominal distention, a massively dilated ascending and transverse colon, and a normal calibre rectum and descending and sigmoid colon. He had a high titre of circulating serum anti-neuronal nuclear antibodies. METHODS: Histology, immunocytochemistry (for neurofilaments, neurone specific enolase, synaptophysin, glial fibrillar acidic protein, S100 protein, and smooth muscle alpha-actin), and electron microscopic examinations on the resected colon. RESULTS: The number of ganglion cells and nerve trunks was decreased throughout the colon. Disruption of the neural network and a loss of interstitial cells of Cajal were observed on the luminal side of the circular muscle; in their place, the non-dilated colon contained a hypertrophic fibromuscular layer. CONCLUSIONS: Striking architectural alterations occurred at the site regarded as the source of the coordination of colonic circular muscle activity in an adult patient with acquired intestinal hypoganglionosis presenting as megacolon.

Adult↗

Clinical relevance of expression of the CIP/KIP cell-cycle inhibitors p21 and p27 in laryngeal cancer.

PURPOSE: To investigate the prognostic relevance of p21 and p27 protein expression in laryngeal squamous cell carcinoma (LSCC). PATIENTS AND METHODS: We have analyzed by immunohistochemistry p21 and p27 expression in a series of 132 patients who underwent surgical resection of their LSCC and who had previously been investigated for p53 gene mutations and cyclin D1 expression. The tumors were considered low expressors when they had </= 10% of p21 and </= 50% of p27 immunoreactive neoplastic cells. RESULTS: In 41 cases (31.1%), p21 was expressed in </= 10% of neoplastic cells; in 91 cases (68.9%), it was expressed in more than 10% of neoplastic cells. In 11 cases (8.3%), p27 was expressed in less than 5% of neoplastic cells; in 39 cases (29.6%), it was expressed in 5% to 50% of neoplastic cells; and in 82 cases (62.1%), it was expressed in more than 50% of the neoplastic cells. Low levels of p21 expression were associated with poor histologic differentiation and lymph node metastases. Low levels of p27 expression were associated with tumor extension and advanced clinical stage. Expression of p21 and p27 was not correlated with p53 gene status, and low p27 expression was more frequently detected in the cyclin D1-positive cases, with a borderline level of statistical significance. At univariate analysis, anatomic site, tumor extension, clinical stage, high cyclin D1 expression, and low p27 expression were significantly associated with reduced disease-free and overall survival rates. At multivariate analysis, high cyclin D1 expression and low p27 expression were the only significant covariates. The patients with a cyclin D1(+)/p27(-) phenotype had the poorest disease-free and overall survival rates. CONCLUSION: Our study provides evidence that the immunohistochemical evaluation of p27 expression is a significant independent predictor of prognosis in laryngeal carcinoma.

Adult↗

Clinical relevance of p53 and bcl-2 protein over-expression in laryngeal squamous-cell carcinoma.

We investigated immunohistochemically the clinical relevance of the over-expression of the apoptosis-regulating proteins p53 and bcl-2 in a homogeneous series of 149 laryngeal squamous-cell carcinomas. p53 was over-expressed in 75 cases and bcl-2 in 39 cases. p53 and bcl-2 co-expression was found in 21 cases. p53 and bcl-2 immunoreactivity was significantly associated with poor histological differentiation and lymph-node metastases. Moreover, a significant statistical correlation was found between bcl-2 expression, supraglottic tumor site and advanced disease stage. p53/bcl-2 co-expression was significantly associated with poor differentiation, tumor extension, the presence of lymph-node metastases and advanced clinical stage. Univariate analysis showed that a lower probability of survival was significantly associated with supraglottic site, tumor extension, advanced clinical stage and p53/bcl-2 co-expression, but not with p53 or bcl-2 considered separately. In multivariate analysis, only tumor extension and supraglottic site retained their prognostic value. Our data suggest that clinical staging remains the most reliable predictive indicator of survival in patients with laryngeal carcinoma.

Adult↗

Chromogranin A and B and secretogranin II in prostatic adenocarcinomas: neuroendocrine expression in patients untreated and treated with androgen deprivation therapy.

BACKGROUND: Neuroendocrine (NE) expression in prostatic adenocarcinomas (PACs) has been related to an adverse clinical course, but the reported data are not unequivocal. METHODS: We immunostained a series of 64 PACs with three monoclonal antibodies raised against chromogranin A (CgA), chromogranin B (CgB), and secretogranin II (SgII). The patients were followed up for 18-88 months (mean 43 months, standard deviation +/- 20 months); 58 of them received preoperative androgen deprivation therapy for 3-6 months. RESULTS: Of the 64 PACs under study, 39 (approximately 61%) were immunoreactive to CgA, 51 (approximately 80%) to CgB, and 38 (approximately 59%) to SgII. We found a strict correlation between pronounced neuroendocrine differentiation and the most poorly differentiated tumors (P = 0.01 for CgA, P = 0.03 for CgB, and P = 0.05 for SgII), and relationship (approaching statistical significance only for CgB, P = 0.07) between Cgs/Sg expression and advanced (C and D) clinical stage. However, we failed to detect any correlation between chromogranin expression and clinical outcome. CONCLUSIONS: These results suggest that NE differentiation is a frequent event in PACs, especially in the most poorly differentiated. Nevertheless, as Cgs/Sg expression is not clearly related to advanced clinical stage and poor prognosis, our findings suggest that clinical staging and grading, rather than NE differentiation, remain the most powerful prognostic indicators in PACs.

Adenocarcinoma↗

Organ culture in 3-dimensional matrix: in vitro model for evaluating biological compliance of synthetic meshes for abdominal wall repair.

A new in vitro method to evaluate the early critical interactions between synthetic prosthetic materials and growing tissues is reported. The correct spatial organization and proper cell to cell interaction required to mimic the in vivo environment was obtained in a 3-dimensional (3-D) embryo organ culture. The clot formed by plasma and chick-embryo extract provided a natural 3-D extracellular matrix that was able to support the growth and differentiation of intestinal tissue dissected from 12-day-old chick embryos. Different materials used for the repair of abdominal wall defects were taken as standards; all the prosthetic materials were devoid of any evident cytotoxic potential over a 10-day culture period, so they did not interfere with the organogenesis process. A polyglactin mesh (Vicryl) was fully incorporated into the growing tissue, but early signs of its degradation were detectable. The biologically inert materials polyethylene terephthalate (Mersilene) and polypropylene (Marlex, Prolene, and Herniamesh) retained their structural integrity when incubated with cultured tissue at 37 degrees C, and they did not hinder cellular proliferation or fibroblast migration. However, the outgrowth behavior was very different while the connective tissue invaded the interstices of the polyethylene terephthalate mesh; the explants and the migrating cells were repelled by hydrophobic polypropylene meshes. These findings are in agreement with other reported results in in vivo studies. Therefore, this method can be considered as reliable and predictable for the evaluation of biopolymers.

Abdominal Muscles↗

Low-grade MALT lymphoma involving multiple mucosal sites and bone marrow.

Mucosa-associated lymphoid tissue (MALT) lymphomas are indolent neoplasms which tend to remain localized for a long time before spreading. We describe here the case of a 36-year-old woman with a low-grade MALT lymphoma involving the lung, stomach, lingual tonsil, and bone marrow at the time of diagnosis. The clonal origin of the pulmonary and bone marrow neoplastic infiltrates was assessed by means of gene rearrangement analysis. All of the involved sites were infiltrated by centrocyte- and monocytoid-like cells expressing the B-cell-associated antigens CD19 and CD20 and showed IgM lambda chain restriction; no CD5, CD10, or CD43 expression was detectable. As the patient had a history of recurrent bronchitis, and computed tomography performed 3 years before the lymphoma diagnosis had already revealed a lesion of the left lung, we conclude that the present case probably represents a pulmonary low-grade MALT lymphoma characterized by an early and unusual involvement of different mucosal sites and bone marrow.

Adult↗

The predictive value of p53, MDM-2, cyclin D1 and Ki67 in the progression from low-grade dysplasia towards carcinoma of the larynx.

To evaluate the predictive role of the oncogenes p53, MDM-2 and cyclin D1, and the proliferative marker Ki67, in the progression from low-grade dysplasia to carcinoma of the larynx. We studied immunohistochemically a series of 32 low-grade pre-neoplastic laryngeal lesions, 10 of which progressed to invasive carcinoma. Immunoreactivity in more than 10 per cent of the dysplastic cells was detected in five cases immunostained with anti-p53 (approximately 15 per cent), in two with anti-MDM-2 (approximately six per cent), and 11 with anti-Ki67 antibodies (approximately 34 per cent), whereas none of the cases showed cyclin D1 overexpression. No significant association was found between p53 and MDM-2 immunoreactivity and the evolution to carcinoma; on the contrary, Ki67 expression was detectable in all but one of the 10 cases developing an infiltrative tumour (90 per cent), and in two of the 22 cases that did not progress (approximately nine per cent) (p = 0.01). These findings indicate that immunohistochemical assessment of the proliferative index in bioptic samples of dysplastic laryngeal mucosa may be useful in selecting patients who should undergo a more specific follow-up evaluation.

Adult↗

Clinical relevance of cyclin D1 protein overexpression in laryngeal squamous cell carcinoma.

PURPOSE: To investigate the prognostic relevance of cyclin D1 gene overexpression in laryngeal squamous cell carcinomas (LSCCs). PATIENTS AND METHODS: The overexpression of cyclin D1 was analyzed in 149 LSCC patients with a median follow-up duration of 60 months using the DCS6 monoclonal antibody; only cases that overexpressed cyclin D1 in more than 5% of neoplastic cells were considered positive. RESULTS: Forty-eight cases (32.2%) were immunoreactive to the DCS6 antibody. Cyclin D1 overexpression was significantly associated with tobacco smoking and alcohol consumption, tumor extension, advanced clinical stage, and the presence of lymph node metastases. Univariate analysis showed that a shorter disease-free and overall survival were significantly associated with supraglottic site, tumor extension, advanced clinical stage, and cyclin D1 overexpression. At multivariate analysis, tumor extension and cyclin D1 overexpression were significantly associated with tumor recurrence, whereas tumor extension, supraglottic site and, at a borderline level of statistical significance, cyclin D1 overexpression, were associated with reduced overall survival. CONCLUSION: The overexpression of cyclin D1 in LSCC is associated with unfavorable clinicopathologic features and represents an independent significant predictor of laryngeal carcinoma prognosis, particularly for disease-free survival. This indicates that cyclin D1 evaluation may be a further useful element for selecting subgroups of patients who should be treated with more aggressive therapies.

Adult↗

Plasmablastic lymphoma of the stomach. A case report.

We report the case of a 53 year-old woman with a gastric tumor showing morphological, phenotypical and molecular features of a plasmablastic lymphoma, a recently recognized subtype of diffuse large B-cell lymphoma. The tumor was composed of plasmablast-like cells, lacked CD45 and B-cell associated antigens, expressed the plasma cell-associated antigen CD38, and showed clonally rearranged IgH genes in the absence of bcl-2 and bcl-6 genes rearrangement.

Female↗

Molecular and immunohistochemical analysis of the bcl-1/cyclin D1 gene in laryngeal squamous cell carcinomas: correlation of protein expression with lymph node metastases and advanced clinical stage.

BACKGROUND: The molecular pathogenesis of laryngeal squamous cell carcinomas (LSCCs) is still only partially understood, although genetic alterations affecting various protooncogenes or tumor suppressor genes have often been detected. METHODS: To improve their understanding of the role of cyclin D1 in the pathogenesis of LSCCs, the authors investigated the expression of cyclin D1 protein and the amplification status of the bcl-1/cyclin D1 locus in a panel of 58 pathologic samples. RESULTS: Expression of cyclin D1 protein was detected in 23 of the 58 patients (approximately 39%), 14 of whom had lymph node metastases (approximately 61%); of the remaining 35 patients without any detectable cyclin D1 expression, 7 had lymph node metastases (20%). Expression of cyclin D1 was detectable in 5% of the specimens of normal mucosa, 13% of those with mild-to-moderate dysplasia, and 25% of those with severe dysplasia. Amplification of the bcl-1/cyclin D1 locus was detected in 12 of the 49 LSCCs investigated (approximately 24%), 7 of which had lymph node metastases (approximately 58%); of the remaining 37 LSCCs with an apparently normal copy number of the cyclin D1 locus, 12 had lymph node metastases (approximately 32%). The authors found almost complete concordance between locus amplification and protein expression. Statistical analysis showed a correlation between cyclin D1 expression and both the presence of lymph node metastases (P < 0.01) and advanced clinical stage (P < 0.02). CONCLUSIONS: The authors' observations suggest that the deregulation of cyclin D1 expression may be involved in the pathogenesis of more aggressive LSCCs.

Adult↗