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Dive into the research topics where Mario Budroni is active.

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Featured researches published by Mario Budroni.


The Journal of Pathology | 2004

Distribution and significance of 14-3-3σ, a novel myoepithelial marker, in normal, benign, and malignant breast tissue

Peter T. Simpson; Theodora Gale; Jorge S. Reis-Filho; Chris Jones; Suzanne Parry; Dawn Steele; Antonio Cossu; Mario Budroni; Giuseppe Palmieri; Sunil R. Lakhani

14‐3‐3σ is a candidate tumour suppressor gene transactivated by p53 in response to DNA damage. In gene expression analysis of normal luminal and myoepithelial cells, 14‐3‐3σ was preferentially expressed by myoepithelial cells. This study has analysed the immunohistochemical distribution and subcellular localization of 14‐3‐3σ in normal breast tissue and in a large series of benign and malignant breast lesions on whole tissue sections and by tissue microarray. Immunohistochemistry demonstrated that 14‐3‐3σ was consistently expressed in the cytoplasmic compartment and occasionally in the nuclei of myoepithelial cells arranged as a continuous layer around normal ducts and lobular units, whereas luminal epithelial, stromal, endothelial, pericytic, lipomatous, and neural cells showed no staining. Myoepithelial cells of benign proliferations and pre‐invasive lesions were consistently positive for 14‐3‐3σ. Strong expression of 14‐3‐3σ was evident in one case of ductal carcinoma in situ (5.5%) and in 105/554 invasive cancers (18.9%). Survival data were available for 452 patients with invasive breast carcinoma. 14‐3‐3σ cytoplasmic subcellular localization was a statistically significant prognostic factor for the whole series of invasive carcinomas, as well as for those positive for oestrogen (ER) or progesterone receptors (PR). This analysis demonstrates the utility of 14‐3‐3σ as a new adjunct antibody for characterization of myoepithelial cells and myoepithelial lesions and it may be a novel prognostic factor for breast cancer patients. Copyright


Journal of Clinical Oncology | 2004

BRAF Gene Is Somatically Mutated but Does Not Make a Major Contribution to Malignant Melanoma Susceptibility: The Italian Melanoma Intergroup Study

Milena Casula; Maria Colombino; Maria P. Satta; Antonio Cossu; Paolo Antonio Ascierto; Giovanna Bianchi-Scarrà; Daniele Castiglia; Mario Budroni; Carla Rozzo; Antonella Manca; Amelia Lissia; Annangela Carboni; Elisabetta Petretto; Sabrina M. R. Satriano; Gerardo Botti; Michela Mantelli; Paola Ghiorzo; Michael R. Stratton; Fraficesco Tanda; Giuseppe Palmieri

PURPOSE Ocogenic activation of the BRAF gene has been demonstrated to be involved in the pathogenesis of malignant melanoma (MM). In this study, we investigated the contribution of BRAF to melanoma susceptibility, also making a comparison with frequency of CDKN2A germline mutations in MM patients from different areas in Italy. PATIENTS AND METHODS sing a combination of denaturing high-performance liquid chromatography analysis and automated sequencing on genomic DNA from peripheral blood or tumor tissue samples, 569 MM patients (211 from northern Italy and 358 from southern Italy) were screened for BRAF mutations. RESULTS Three BRAF germline sequence variants (M116R, V599E, and G608H) were identified in four (0.7%) of 569 MM patients. The most common BRAF mutation, V599E, was detected in one germline DNA sample only; M116R and G608H were newly described mutations. A high frequency (59%) of BRAF mutations was instead observed in tumor samples from patients also undergoing germline DNA analysis; at the somatic level, substitution of valine 599 was found to account for the majority (88%) of BRAF mutations. We then estimated the germline mutation rates in BRAF and CDKN2A among 358 consecutively collected patient samples originating in southern Italy; a low (2.5%) or very low (0.29%) prevalence of CDKN2A and BRAF mutations, respectively, was detected. CONCLUSION utation analysis of either blood DNA from a large collection of MM patients or matched MM tissues from a subset of such patients revealed that BRAF is somatically mutated and does not play a major role in melanoma susceptibility. The present study further suggests that patient origin may account for different mutation rates in candidate genes.


European Journal of Cancer | 2013

High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease.

Pamela Minicozzi; Franco Berrino; Federica Sebastiani; Fabio Falcini; Rosa Vattiato; Francesca Cioccoloni; Gioia Calagreti; Mario Fusco; Maria Francesca Vitale; Rosario Tumino; Aurora Sigona; Mario Budroni; Rosaria Cesaraccio; Giuseppa Candela; Tiziana Scuderi; Maurizio Zarcone; Ildegarda Campisi; Milena Sant

PURPOSE We investigated the effect of fasting blood glucose and body mass index (BMI) at diagnosis on risk of breast cancer death for cases diagnosed in five Italian cancer registries in 2003-2005 and followed up to the end of 2008. METHODS For 1607 Italian women (≥15 years) with information on BMI or blood glucose or diabetes, we analysed the risk of breast cancer death in relation to glucose tertiles (≤84.0, 84.1-94.0, >94.0 mg/dl) plus diabetic and unspecified categories; BMI tertiles (≤23.4, 23.5-27.3, >27.3 kg/m(2), unspecified), stage (T1-3N0M0, T1-3N+M0 plus T4anyNM0, M1, unspecified), oestrogen (ER) and progesterone (PR) status (ER+PR+, ER-PR-, ER and PR unspecified, other), age, chemotherapy and endocrine therapy, using multiple regression models. Separate models for ER+PR+ and ER-PR- cases were also run. RESULTS Patients often had T1-3N0M0, ER+PR+ cancers and received chemotherapy or endocrine therapy; only 6% were M1 and 17% ER-PR-. Diabetic patients were older and had more often high BMI (>27 kg/m(2)), ER-PR-, M1 cancers than other patients. For ER+PR+ cases, with adjustment for other variables, breast cancer mortality was higher in women with high BMI than those with BMI 23.5-27.3 kg/m(2) (hazard ratio (HR)=2.9, 95% confidence interval (CI) 1.2-6.9). Breast cancer mortality was also higher in women with high (>94 mg/dl) blood glucose compared to those with glucose 84.1-94.0mg/dl (HR=2.6, 95% CI 1.2-5.7). CONCLUSION Our results provide evidence that in ER+PR+ patients, high blood glucose and high BMI are independently associated with increased risk of breast cancer death. Detection and correction of these factors in such patients may improve prognosis.


BMC Cancer | 2009

Role of key-regulator genes in melanoma susceptibility and pathogenesis among patients from South Italy

Milena Casula; Antonio Muggiano; Antonio Cossu; Mario Budroni; Corrado Caracò; Paolo Antonio Ascierto; Elena Pagani; Ignazio Stanganelli; Sergio Canzanella; Maria Cristina Sini; Grazia Palomba; Giuseppe Palmieri

BackgroundSeveral genetic alterations have been demonstrated to contribute to the development and progression of melanoma. In this study, we further investigated the impact of key-regulator genes in susceptibility and pathogenesis of such a disease.MethodsA large series (N = 846) of sporadic and familial cases originating from South Italy was screened for germline mutations in p16CDKN2A, BRCA2, and MC1R genes by DHPLC analysis and automated DNA sequencing. Paired primary melanomas and lymph node metastases from same patients (N = 35) as well as melanoma cell lines (N = 18) were analyzed for somatic mutations in NRAS, BRAF, and p16CDKN2Agenes.ResultsFor melanoma susceptibility, investigations at germline level indicated that p16CDKN2Awas exclusively mutated in 16/545 (2.9%) non-Sardinian patients, whereas BRCA2 germline mutations were observed in 4/91 (4.4%) patients from North Sardinia only. Two MC1R germline variants, Arg151Cys and Asp294His, were significantly associated with melanoma in Sardinia. Regarding genetic events involved in melanoma pathogenesis at somatic level, mutually-exclusive mutations of NRAS and BRAF genes were observed at quite same rate (about two thirds) in cultured and in vivo melanomas (either primary or metastatic lesions). Conversely, p16CDKN2Agene alterations were observed at increased rates moving from primary to metastatic melanomas and melanoma cell lines. Activation of the ERK gene product was demonstrated to be consistently induced by a combination of molecular alterations (NRAS/BRAF mutations and p16CDKN2Asilencing).ConclusionOur findings further clarified that: a) mutation prevalence in melanoma susceptibility genes may vary within each specific geographical area; b) multiple molecular events are accumulating during melanomagenesis.


Thyroid | 2012

Changes in the Incidence of Thyroid Cancer Between 1991 and 2005 in Italy: A Geographical Analysis

Mauro Lise; Silvia Franceschi; Carlotta Buzzoni; Paola Zambon; Fabio Falcini; Emanuele Crocetti; Diego Serraino; Francesco Iachetta; Roberto Zanetti; Marina Vercelli; Stefano Ferretti; Francesco La Rosa; Andrea Donato; Vincenzo De Lisi; Lucia Mangone; Susanna Busco; Giovanna Tagliabue; Mario Budroni; Luigi Bisanti; Mario Fusco; Rosa Maria Limina; Rosario Tumino; Silvano Piffer; Anselmo Madeddu; Francesco Bellù; Adriano Giacomin; Giuseppa Candela; Monica Lucia Anulli; Luigino Dal Maso

BACKGROUND The incidence of thyroid cancer (TC) has been increasing over the last 30 years in several countries, with some of the worldwide highest TC incidence rates (IRs) reported in Italy. The objectives of this study were to evaluate by histological subtypes the geographical heterogeneity of the incidence of TC in Italy and to analyze recent time trends for papillary thyroid carcinoma (PTC) in different cancer registries (CRs). METHODS The study included cases of TC (<85 years of age) reported to 25 Italian CRs between 1991 and 2005. Age-standardized IRs were computed for all histological subtypes of TC according to CRs. Estimated annual percent change and joinpoint regression analysis were used for analysis of PTC. RESULTS In women, IRs of PTC ranged between 3.5/100,000 in Latina and 8.5/100,000 in Sassari for the period 1991-1995 (a 2.4-fold difference) and between 7.3/100,000 in Alto Adige and 37.5/100,000 in Ferrara for 2001-2005 (a 5.1-fold difference). In men, IRs ranged between 0.7/100,000 in Latina and 3.4/100,000 in Sassari for the period 1991-1995 (a 4.9-fold difference) and between 2.0/100,000 (Alto Adige, Trento) and 10.6/100,000 in Ferrara for 2001-2005 (a 5.3-fold difference). In both sexes, IRs significantly higher than the pooled estimates emerged for the most recent period in the majority of CRs located within the Po River plain and in Latina, but they were lower in the Alpine belt. For women, CRs reported higher IRs than pool estimates showed, between 1991 to 2005, a significantly more marked annual percent change (+12%) than other CRs (+7%). For men the corresponding estimates were +11% and +8%. CONCLUSIONS The distribution of PTC does not lend support to a role of environmental radiation exposure due to the Chernobyl fallout, iodine deficiency, or (volcanic) soils. Between 1991 and 2005, wide geographic variations in the incidence of PTC and heterogeneous upward trends emerged, suggesting that the heterogeneity was a relatively recent phenomenon; this appeared to be mainly explained by variations, at a local level, in medical surveillance.


Multidisciplinary Respiratory Medicine | 2013

Lung cancer epidemiology in North Sardinia, Italy

Panagiotis Paliogiannis; Federico Attene; Antonio Cossu; Mario Budroni; Rosaria Cesaraccio; Francesco Tanda; Mario Trignano; Giuseppe Palmieri

BackgroundThe aim of this study was to analyze and describe the epidemiological characteristics and trends of lung cancer in North Sardinia, Italy, in the period 1992–2010.MethodsData were obtained from the tumor registry of Sassari province which is a part of a wider registry web, coordinated today by the Italian Association for Tumor Registries.ResultsThe overall number of lung cancer cases registered was 4,325. The male-to-female ratio was 4.6:1 and the mean age 68.1 years for males and 67 years for females. The standardized incidence rates were 73.1/100,000 and 13.5/100,000 and the standardized mortality rates 55.7/100,000 and 9.9/100,000 for males and females, respectively. An increasing trend in incidence of lung cancer in women was evidenced. Conversely, incidence was found to decrease in males. Relative survival at 5 years from diagnosis was low (8.8% for males and 14.9% for females). Furthermore, an increase in mortality rates was observed in both sexes in the period under investigation.ConclusionsOur data show an increasing trend of lung cancer incidence in women in North Sardinia in the last decades. Conversely, a reduction of incidence rates was observed in males. Furthermore, a slightly increasing trend in mortality rates was observed in both sexes, suggesting the need to enhance smoking control strategies, consider adoption of effective surveillance policies, and improve diagnosis and treatment methods.


Cancer | 2005

Spectrum and prevalence of BRCA1 and BRCA2 germline mutations in Sardinian patients with breast carcinoma through hospital-based screening

Grazia Palomba; Marina Pisano; Antonio Cossu; Mario Budroni; Maria F. Dedola; Antonio Farris; Antonio Contu; Paola Baldinu; Francesco Tanda; Giuseppe Palmieri

Factors that are predictive of carrying BRCA1 and BRCA2 germline mutations in patients with breast carcinoma are awaited widely. The genetically homogeneous Sardinian population may be useful for defining the role of such genetic alterations further through a clinical evaluation program.


Journal of Translational Medicine | 2012

Prevalence of KRAS, BRAF, and PIK3CA somatic mutations in patients with colorectal carcinoma may vary in the same population: clues from Sardinia

Grazia Palomba; Maria Colombino; Antonio Contu; B. Massidda; Giovanni Baldino; Antonio Pazzola; Maria Teresa Ionta; Francesca Capelli; Vittorio Trova; Tito Sedda; Giovanni Sanna; Francesco Tanda; Mario Budroni; Giuseppe Palmieri; Antonio Cossu

BackgroundRole of KRAS, BRAF and PIK3CA mutations in pathogenesis of colorectal cancer (CRC) has been recently investigated worldwide. In this population-based study, we evaluated the incidence rates and distribution of such somatic mutations in genetically isolated population from Sardinia.MethodsFrom April 2009 to July 2011, formalin-fixed paraffin-embedded tissues (N = 478) were prospectively collected from Sardinian CRC patients at clinics across the entire island. Genomic DNA was isolated from tissue sections and screened for mutations in KRAS, BRAF, and PIK3CA genes by automated DNA sequencing.ResultsOverall, KRAS tumour mutation rate was 30% (145/478 positive cases). Distribution of mutation carriers was surprisingly different within the island: 87/204 (43%) in North Sardinia vs. 58/274 (21%) in Middle-South Sardinia (p<0.001). Among 384 CRC cases whose DNA was available, only one (0.3%) patient carried a mutation in BRAF gene; PIK3CA was found mutated in 67 (17%) patients. A significant inverse distribution of PIK3CA mutation rates was observed within Sardinian population: 19/183 (10%) cases from northern vs. 48/201 (24%) cases from central-southern island (p<0.001). This heterogeneity in frequencies of KRAS/PIK3CA somatic mutations is consistent with already-reported discrepancies in distribution of germline mutations for other malignancies within Sardinian population. Preliminary clinical evaluation of 118 KRAS wild-type patients undergoing anti-EGFR-based treatment indicated lack of role for PIK3CA in predicting response to therapy.ConclusionsOur findings support the hypothesis that differences in patients’ origins and related genetic backgrounds may contribute to even determine the incidence rate of somatic mutations in candidate cancer genes.


Journal of Cancer Epidemiology | 2013

Epidemiology of Thyroid Cancer in an Area of Epidemic Thyroid Goiter

Antonio Cossu; Mario Budroni; Panagiotis Paliogiannis; Giuseppe Palmieri; Fabrizio Scognamillo; Rosaria Cesaraccio; Federico Attene; Mario Trignano; Francesco Tanda

The aim of this study was to analyze and describe the epidemiological characteristics and trends of thyroid cancer in the province of Sassari (Sardinia, Italy), an area with epidemic thyroid goiter, in the period 1992–2010. Data were obtained from the local tumor registry which makes part of a wider registry web, coordinated today by the Italian Association for Tumor Registries. An increasing trend in the incidence of thyroid cancer in the province of Sassari was evidenced. This trend seems to follow the general worldwide trend and does not seem to be related to the high incidence of thyroid goiter in the area. The frequencies of the different histological subtypes were similar to those reported in numerous national and international reports. Women are affected earlier than men and, therefore, suffer greater professional, economic, and social impacts. Overall mortality is low and a relative 5-year survival is excellent, especially in comparison to other malignancies.


BMC Cancer | 2009

A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population

Grazia Palomba; Angela Loi; Antonella Uras; Patrizia Fancello; Giovanna Piras; Attilio Gabbas; Antonio Cossu; Mario Budroni; Antonio Contu; Francesco Tanda; A. Farris; Sandra Orrù; Carlo Floris; Marina Pisano; Mario Lovicu; Maria Cristina Santona; Gennaro Landriscina; Laura Crisponi; Giuseppe Palmieri; Maria Monne

BackgroundIn recent years, numerous studies have assessed the prevalence of germline mutations in BRCA1 and BRCA2 genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of BRCA1-2 mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of BRCA1-2 germline mutations was also evaluated.MethodsThree hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for BRCA1-2 mutations by DHPLC analysis and DNA sequencing. Association of BRCA1 and BRCA2 mutational status with clinical and pathological parameters was evaluated by Pearsons Chi-Squared test.Results and ConclusionOverall, 8 BRCA1 and 5 BRCA2 deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in BRCA2 gene. The geographical distribution of BRCA1-2 mutations was related to three specific large areas of Sardinia, reflecting its ancient history: a) the Northern area, linguistically different from the rest of the island (where a BRCA2 c.8764_8765delAG mutation with founder effect was predominant); b) the Middle area, land of the ancient Sardinian population (where BRCA2 mutations are still more common than BRCA1 mutations); and c) the South-Western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of BRCA1-2 germline mutations.

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Grazia Palomba

National Research Council

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Maria Colombino

National Research Council

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Marina Pisano

National Research Council

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