Carraro D.M.,National Institute of Science and Technology in Oncogenomics INCITO |
Andrade V.P.,Ac Camargo Cancer Center
Bioscience Reports | Year: 2014
The spread of mammographic screening programmes around the world, including in developing countries, has substantially contributed to the diagnosis of small non-palpable lesions, which has increased the detection rate of DCIS (ductal carcinoma in situ). DCIS is heterogeneous in several ways, such as its clinical presentation, morphology and genomic profile. Excellent outcomes have been reported; however, many questions remain unanswered. For example, which patients groups are overtreated and could instead benefit from minimal intervention and which patient groups require a more traditional multidisciplinary approach. The development of a comprehensive integrated analysis that includes the radiological, morphological and genetic aspects of DCIS is necessary to answer these questions. This review focuses on discussing the significant findings about the morphological and molecular features of DCIS and its progression that have helped to uncover the biological and genetic heterogeneity of this disease. The knowledge gained in recent years might allow the development of tailored clinical management for women with DCIS in the future. © 2014 The Author(s).
Silva S.D.,McGill University |
Silva S.D.,Ac Camargo Cancer Center |
Alaoui-Jamali M.A.,McGill University |
Hier M.,McGill University |
And 3 more authors.
Clinical and Experimental Metastasis | Year: 2014
Overexpression of members of the ErbB receptor family is common in oral squamous cell carcinomas (OSCC); however, their prognostic value for aggressive OSCC has been debated. Extranodal spread to cervical lymph nodes is the most significant prognostic indicator in OSCC. In the present study, we investigated the clinical significance of single versus paired overexpression of members of the ErbB receptor family in 82 OSCC patients with lymph nodes metastasis, with or without capsular rupture (CR) followed by at least 10 years. Immunohistochemistry analysis revealed a common overexpression of ErbB1 (P = 0.021), ErbB2 (P = 0.001), ErbB4 (P = 0.048), as well as MMP-2 (P = 0.043) in OSCC cases with CR+. Increased expression of ErbB1 was associated with MMP-2 in tumors with advanced clinical stages, including poorly differentiated (grade III) tumors (P < 0.050). Vascular embolization was associated with MMP-2 (P = 0.021) and MMP-13 (P = 0.010) overexpression. Survival analysis revealed a lower survival probability in tumors over-expressing ErbB1 (P = 0.038), ErbB4 (P = 0.043), and MMP-12 (P = 0.050). As well a strong association was observed in cases with high risk of recurrence and strong immunostaining for ErbB1 (P = 0.017), ErbB4 (P = 0.008), MMP-1 (P = 0.003), MMP-2 (P = 0.016), MMP-10 (P = 0.041), and MMP-13 (P = 0.005). Stratified multivariate survival analysis revealed a strong prognostic interdependence of ErbB1 and ErbB4 cooverexpression in predicting the worst overall and disease-free survivals (P = 0.0013 and P = 0.0004, respectively). Taken together, these results support a cooperation of ErbB1, ErbB4, and members of the MMP family in predicting OSCC invasion and poor clinical outcomes. © Springer Science+Business Media 2013.
Lourenco S.V.,University of Sao Paulo |
Fernandes J.D.,Federal University of Bahia |
Hsieh R.,University of Sao Paulo |
Coutinho-Camillo C.M.,Ac Camargo Cancer Center |
And 3 more authors.
American Journal of Dermatopathology | Year: 2014
Head and neck mucosal melanoma (MM) is an aggressive and rare neoplasm of melanocytic origin. To date, few retrospective series and case reports have been reported on MM. This article reviews the current evidence on head and neck MM and the molecular pathways that mediate the pathogenesis of this disease. Head and neck MM accounts for 0.7%-3.8% of all melanomas and involve (in decreasing order of frequency) the sinonasal cavity, oral cavity, pharynx, larynx, and upper esophagus. Although many studies have examined MM of the head and neck and the underlying molecular pathways, individual genetic and molecular alterations were less investigated. Further studies are needed to complement existing data and to increase our understanding of melanocytes tumorigenesis. © 2014 Lippincott Williams & Wilkins.
Bines J.,Instituto Nacional Of Cancer |
Dienstmann R.,Fred Hutchinson Cancer Research Center |
Obadia R.M.,Instituto Nacional Of Cancer |
Branco L.G.P.,Instituto Nacional Of Cancer |
And 6 more authors.
Annals of Oncology | Year: 2014
Background: As novel treatments carry substantial price tags and are mostly cost-prohibitive in low-and middleincome countries, there is an urgent need to develop alternatives, such as off-patent drugs. Megestrol acetate (MA) has a longstanding history in the treatment of breast cancer, but recently it is being used less often due to the advent of newer agents. Patients and methods: This two-stage phase II trial evaluated the antitumor activity and toxicity of MA in postmenopausal women with hormone-sensitive advanced breast cancer who had experienced disease progression on a thirdgeneration nonsteroidal aromatase inhibitor (NSAI). Eligible patients had metastatic breast cancer treated with a NSAI with at least 6-month progression-free survival (PFS), or relapse after =1 year on adjuvant NSAI. Patients received MA at a single daily oral dose of 160 mg. Primary end point was clinical benefit rate (CBR).Results: Forty-eight patients were enrolled. The CBR was 40% [95% confidence interval (CI) 25% to 55%], and the median duration of clinical benefit was 10.0 (95% CI 8.0-14.2) months. The median PFS was 3.9 (95% CI 3.0-4.8) months. The most common grade 3 adverse events were anemia (2%), dyspnea (2%), fatigue (2%), musculoskeletal pain (4%), deep vein thrombosis (10%), and weight gain (2%). Conclusions: This is the first study to prospectively evaluate the efficacy and safety of MA in postmenopausal women with hormone-sensitive disease progressing on a NSAI. MA has demonstrated activity and acceptable tolerability in this setting, and therefore remains a reasonable treatment option in a cost-sensitive environment. These results also provide the background for further evaluation of progestins in the treatment of breast cancer. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Dal Sasso A.A.,Federal University of Rio de Janeiro |
Belem L.C.,Federal University of Rio de Janeiro |
Zanetti G.,Federal University of Rio de Janeiro |
Souza C.A.,University of Ottawa |
And 5 more authors.
Respiratory Medicine | Year: 2015
Background: Birt-Hogg-Dubé syndrome (BHDS) is a rare, inherited autosomal-dominant disorder characterized by the development of cutaneous lesions, renal tumors, pulmonary cysts, and spontaneous pneumothorax. The gene responsible for BHDS is located on the short arm of chromosome 17 (17p11.2) and codes for the protein folliculin, which is believed to be an oncogene suppressor protein. Methods: We reviewed currently published literature on the main characteristics of BHDS. Results: Pulmonary cysts and spontaneous pneumothorax are often the presenting manifestations that lead to a final diagnosis in family members affected by the syndrome. Conclusions: Certain imaging characteristics of pulmonary cysts, including size and location, can suggest the diagnosis of BHDS based on chest computed tomography alone. The main concern in patients with BHDS is the increased risk of renal carcinoma. The aim of this review is to describe the main pathological, clinical, and imaging aspects of BHDS, ranging from its genetic basis to treatment, with emphasis on pulmonary involvement. © 2014 Elsevier Ltd. All rights reserved.
Jaguar G.C.,Ac Camargo Cancer Center |
Lima E.N.P.,Ac Camargo Cancer Center |
Kowalski L.P.,Ac Camargo Cancer Center |
Pellizzon A.C.,Ac Camargo Cancer Center |
And 3 more authors.
Radiotherapy and Oncology | Year: 2015
This study assessed the prophylactic bethanechol use to prevent salivary gland dysfunction during radiotherapy. A total of 97 head and neck cancer patients were allocated into two groups: Bethanechol or Placebo. Bethanechol group presented significantly improve of salivary parameters. Bethanechol was effective in decreasing the salivary gland damage. © 2015 Elsevier Ireland Ltd. All rights reserved.
Castro R.P.,Ac Camargo Cancer Center |
Stephens A.,Skin and Cancer Associations |
Fraga-Braghiroli N.A.,Skin and Cancer Associations |
Oliviero M.C.,Skin and Cancer Associations |
And 4 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2015
Background Reflectance confocal microscopy (RCM) increases specificity of identification of basal cell carcinoma (BCC). A smaller-diameter handheld RCM (HH-RCM) allows better access to limited anatomic locations. Objective To compare accuracy of HH-RCM in identification of BCC to that of traditional wide-probe RCM (TWP-RCM). Methods Patients presenting at least one lesion clinically and dermoscopically suspicious for BCC, were recruited from two dermatology skin cancer clinics. Prior to excision, we attempted to image all lesions with HH-RCM and TWP-RCM using a standardized protocol. RCM images were retrospectively evaluated, jointly by two blinded readers. For purposes of comparative RCM, sensitivity and specificity analysis, we used a threshold of ≥3 RCM criteria to identify BCC, whereby at least one criterion had to be presence of 'dark silhouettes' or 'bright tumor islands'. Results Among 54 lesions imaged with both RCM devices, 45 were biopsy-proven BCCs. Comparison between TWP-RCM vs. HH-RCM was as follows: sensitivity (100% vs. 93%), specificity (78% for both probes), positive predictive value (96% vs. 95%), and negative predictive value (100% vs. 70%) respectively. Notably, both TWP-RCM and HH-RCM demonstrated the presence of 'dark silhouettes' or 'bright tumor islands' in all 45 BCCs. Conclusion Both RCM probes demonstrate high PPV. TWP-RCM shows higher NPV, since its broader field-of-view probably allows more exhaustive search for BCC criteria. The RCM criteria threshold for BCC identification should be further tested. © 2014 European Academy of Dermatology and Venereology.
Da Costa W.H.,Ac Camargo Cancer Center |
Rezende M.,Ac Camargo Cancer Center |
Carneiro F.C.,Ac Camargo Cancer Center |
Rocha R.M.,Ac Camargo Cancer Center |
And 4 more authors.
BJU International | Year: 2014
Objective: • To analyse the immunohistochemical and mRNA expression of SWI/SNF (SWItch/Sucrose NonFermentable) complex subunit polybromo-1 (PBRM1) in clear cell renal cell carcinoma (ccRCC) and its impact on clinical outcomes. Patients and Methods: • In all, 213 consecutive patients treated surgically for renal cell carcinoma (RCC) between 1992 and 2009 were selected. • A single pathologist reviewed all cases to effect a uniform reclassification and determined the most representative tumour areas for construction of a tissue microarray. • In addition, mRNA expression of PBRM1 was analysed by reverse transcriptase-polymerase chain reaction. Results: • Of the 112-immunostained ccRCC specimens, 34 (30.4%) were PBRM1-negative, and 78 (69.6%) were PBRM1-positive. • The protein expression of PBRM1 was associated with tumour stage (P < 0.001), clinical stage (P < 0.001), pN stage (P = 0.035) and tumour size (P = 0.002). • PBRM1 mRNA expression was associated with clinical stage (P = 0.023), perinephric fat invasion (P = 0.008) and lymphovascular invasion (P = 0.042). • PBRM1 significantly influenced tumour recurrence and tumour-related death. Disease-specific survival rates for patients whose specimens showed positive- and negative-PBRM1 expression were 89.7% and 70.6%, respectively (P = 0.017). • Recurrence-free survival rates in patients with positive- and negative-expression of PBRM1 were 87.3% and 66.7%, respectively (P = 0.048). Conclusions: • PBRM1-negative expression is a markedly poor prognosis event in ccRCC. • We encourage PBRM1 study by other groups in order to validate our findings and confirm its possible role as a useful marker in the management of patients with ccRCC. © 2013 The Authors.
Bitencourt A.G.V.,Ac Camargo Cancer Center |
Lima E.N.P.,Ac Camargo Cancer Center |
Chojniak R.,Ac Camargo Cancer Center |
Marques E.F.,Ac Camargo Cancer Center |
And 3 more authors.
Medicine (United States) | Year: 2014
The purpose of this study was to evaluate the diagnostic accuracy of multiparametric evaluation of breast lesions combining information of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted imaging (DWI), and 18Ffluoro-deoxi-glucose (18F-FDG) positron emission tomography/computed tomography (PET-CT). After approval of the institutional research ethics committee, 31 patients with suspicious breast lesions on MRI performed 18F-FDG PET-CT with a specific protocol for breast evaluation. Patients' mean age was 47.8 years (range, 29-77 years). Positron emission tomography and magnetic resonance imaging (PET-MRI) images were fused. A lesion was considered positive on multiparametric evaluation if at least 1 of the following was present: washout/type 3 kinetic curve on DCEMRI, restricted diffusion on DWI with minimum apparent diffusion coefficient value <1.00 × 10-3mm2/s, and abnormal metabolism on 18F-FDG PET-CT (higher than the physiologic uptake of the normal breast parenchyma). Thirty-eight lesions with histologic correlation were evaluated on the 31 included patients, being 3 mass lesions (84.2%), and 6 nonmass lesions (15.8%). Lesions' mean diameter was 31.1mm (range, 8-94mm). Multiparametric evaluation provided 100% sensitivity, 55.5% specificity, 87.9% positive predictive value, 100% negative predictive value, and 89.5% accuracy, with 29 true-positives results, 5 true-negatives, false-positives, and no false-negative results. Multiparametric evaluation with PET-MRI functional data showed good diagnostic accuracy to differentiate benign from malignant breast lesions, reducing the number of unnecessary biopsies, without missing any diagnosis of cancer in our case series. Copyright © 2014 Wolters Kluwer Health-Lippincott Williams & Wilkins.
Zanvettor P.H.,Hospital Aristides Maltez |
Falcao Filho D.F.,Hospital Aristides Maltez |
Soares F.A.,Ac Camargo Cancer Center |
Santos Neves A.R.,Hospital Aristides Maltez |
Palmeira L.O.,Hospital Aristides Maltez
International Journal of Gynecological Cancer | Year: 2014
Introduction: Cancers of the vulva account for 3%to 5%of all cancers of the female genital. This study was conducted to evaluate clinical, pathological, andmolecular prognostic factors in patients with cancer of the vulva. Methods: Patients with squamous cell carcinoma of the vulva who had undergone surgical treatment at the Department of Pelvic Surgery and Gynecology Service, Aristides Maltez Hospital, between June 1993 and June 2011 were selected. Clinical, epidemiological, pathological, and molecular characteristics related to the prognosis of these patients were evaluated in relation to the prognosis. In the molecular evaluation, we studied the expression of p53 and matrix metalloproteinase 2 by immunohistochemistry. Results: Seventy-five patients were eligible for the study. In multivariable analysis, factors related to survivalwere as follows: tumor size larger than 4 cm(P = 0.014), an invasion depth greater than 2 mm (P = 0.023) and matrix metalloproteinase 2 expression in more than 50% of the tumor cells (P = 0.046). With the use of the relative risks of the factors identified in the multivariable analysis, a point count was developed for a prognostic classification (the score classifies patients into 3 categories). Conclusions: A tumor size larger than 4 cm, an invasion depth greater than 2 mm, and metalloproteinase 2 expression in more than 50%of the tumor cells seem to be related to lower overall survival rate in patients with cancer of the vulva undergoing surgical treatment. A classification of the patient's prognosis can be performed using a point count based on these relative risks. Copyright © 2014 by IGCS and ESGO.