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Gliomas represent 80% of all primary malignant brain tumors in adults. In view of this public health problem, the early detection through sensitive and specific molecular tumor markers analysis can help to improve gliomas diagnosis and prognosis as well as their staging, assessment of therapeutic response and detection of recurrence. Therefore, this review focuses in current gliomas tumor markers, IDH-1/2, 1p/19q, MGMT, ATRX, TERT, H3, EGFR, BRAF and Ki67 used in clinic worldwide and their importance to early detection, glioma histological and molecular classification as well as in predicting patient's therapeutic response. In addition, we present what are the steps in the requesting process for this type of examination in the Brazilian Public Health System (SUS) scope, which attends most of the Brazilian population. Thereby, this article is useful in demonstrating which markers are used in the clinical practice for glioma patients and can be performed in the SUS through partnerships/agreements between specialized health centers and clinical analysis laboratories. It is hoped that this work clarifies, the necessary subsidies to carry out the research of tumor markers in all institutions that serve SUS users, providing a service with equal conditions.

Genome-wide analysis using microarrays has revolutionized breast cancer (BC) research. A substantial body of evidence supports the clinical utility of the 21-gene assay (Oncotype DX) and 70-gene assay (MammaPrint) to predict BC recurrence and the magnitude of benefit from chemotherapy. However, there is currently no genetic tool able to predict chemosensitivity and chemoresistance to neoadjuvant chemotherapy (NACT) during BC treatment. In this study, we explored the predictive value of DNA repair gene expression in the neoadjuvant setting. We selected 98 patients with BC treated with NACT. We assessed DNA repair expression in 98 formalin-fixed, paraffin-embedded core biopsy fragments used at diagnosis and in 32 formalin-fixed, paraffin-embedded post-NACT residual tumors using quantitative reverse transcription-polymerase chain reaction. The following genes were selected: BRCA1, PALB2, RAD51C, BRCA2, ATM, FANCA, MSH2, XPA, ERCC1, PARP1, and SNM1. Of 98 patients, 33 (33.7%) achieved pathologic complete response (pCR). The DNA expression of 2 genes assessed in pre-NACT biopsies (PALB2 and ERCC1) was lower in pCR than in non-pCR patients (P=0.005 and P=0.009, respectively). There was no correlation between molecular subtype and expression of DNA repair genes. The genes BRCA2 (P=0.009), ATM (P=0.004), FANCA (P=0.001), and PARP1 (P=0.011) showed a lower expression in post-NACT residual tumor samples (n=32) than in pre-NACT biopsy samples (n=98). The expression of 2 genes (PALB2 and ERCC1) was lower in pCR patients. These alterations in DNA repair could be considered suitable targets for cancer therapy.

Literature shows that HER2/neu positive breast cancer cells are more sensitive to radiation-induced apoptosis by targeting the epidermal growth factor receptor family tyrosine kinase. We selected 466 patients with pT1-2 HER2/neu positive tumors who received adjuvant trastuzumab for primary invasive breast cancer. Patients were divided into three groups [Quadrantectomy followed by conventional radiotherapy vs Quadrantectomy followed by Intra-operative radiotherapy with electrons vs Mastectomy without radiotherapy]. After a median follow-up of 52 months, the 5-year cumulative incidence of locoregional recurrence (LRR) was 1.9%, 11.5% and 5.0% respectively (p < 0.01). At the multivariate analysis, extensive perivascular invasion, Luminal B HER2/Progesterone Receptor (PgR) negative status and Quadrantectomy followed by Intra-operative radiotherapy with electrons have significantly increased the risk of LRR. Our results suggest that HER2/neu positive breast cancer might have better outcomes when treated simultaneously with external radiotherapy and trastuzumab. Moreover, we underline the importance of PgR and further new stratification of risk among luminal subtypes., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: A small but significant proportion of patients with breast cancer (BC) will develop loco-regional recurrence (LRR) after immediate breast reconstruction (IBR). The LRR also varies according to breast cancer subtypes and clinicopathological features., Methods: We studied 1742 consecutive BC patients with IBR between 1997 and 2006. According to St Gallen conference consensus 2011, its BC approximations were applied to classify BC into five subtypes: estrogen receptor (ER) and/or progesterone receptor (PgR) positive, HER2 negative, and low Ki67 (<14%) [luminal A]; ER and/or PgR positive, HER2 negative and high Ki67(≥ 14%) [luminal B/HER2 negative]; ER and/or PgR positive, any Ki67 and HER2 positive [luminal B/HER2 positive]; ER negative, PgR negative and HER2 positive [HER2 positive/nonluminal]; and ER negative, PgR negative and HER2 negative [triple negative]. Cumulative incidences of LRR were compared across different subgroups by means of the Gray test. Multivariable Cox regression models were applied., Results: Median follow up time was 74 months (range 3-165). The cumulative incidence of LRR was 5.5% (121 events). The 5-year cumulative incidence of LRR was 2.5% for luminal A; 5.0% for luminal B/HER2 negative; 9.8% for luminal B/HER2 positive; 3.8% for HER2 non luminal; and 10.9% for triple negative. On multivariable analysis, tumor size (pT) >2 cm, body mass index (BMI) ≥ 25, triple negative and luminal B/HER2 positive subtypes were associated with increased risk of LRR., Conclusion: Luminal B/HER2 positive, triple negative subtypes and BMI ≥ 25 are independent prognostic factors for risk of LRR after IBR., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The selections of nipple-sparing mastectomy (NSM) are principally depending on oncologic indication and oncologic safety. The main complication of NSM is nipple areolar complex (NAC) necrosis, and it is usually related to surgical technique. However, the patients' clinicopathological factors should be also considered., Method: We retrospectively reviewed 934 consecutive NSM patients during 2002-2007 at the European Institute of Oncology, Milan, Italy. We identified a group of patient who had NAC excision because of NAC necrosis and compared this group with those who had successful NAC conservation. We analyzed the association between the risk of NAC necrosis and the clinicopathological features of the patients., Results: Among 934 NSM, 772 were invasive cancers and 162 were in situ cancers. Of the 934, 40 NAC (4.2%) were removed during the postoperative period because of necrosis. When we considered age, BMI, menopausal status, smoking status, tumor size, axillary lymph node status, in situ or invasive cancer histology, presence of extensive situ component, grading, estrogen receptor, progesterone receptor, HER2/neu overexpression, Ki-67 proliferative index, and peritumoral vascular invasion, no association was observed between patients' clinicopathological features and NAC necrosis incidence., Conclusions: In our study, clinicopathological features have no significant impact on necrosis complication in therapeutic NSMs. Positive retroareolar margin is the risk of necrosis. Further studies are required to avoid bias due to the different cancer treatments such as different reconstruction techniques and intraoperative radiation protocols. The correlation between breast morphology and NAC necrosis should also be investigated in the future.

Trastuzumab, in combination with chemotherapy, is the gold standard in the adjuvant treatment of patients with HER2 positive breast cancer. Limited data are available on the role of adjuvant trastuzumab in the elderly population. We performed a systematic review of prospective randomized trials with available data on the use of adjuvant trastuzumab in patients older than 60years, focusing on both the efficacy and the cardiac safety. Data extrapolated from two prospective trials were included for efficacy and cardiac safety. A significant 47% relative risk reduction was observed in elderly patients receiving trastuzumab compared to chemotherapy alone (pooled Hazard Ratio: 0.53; 95% CI, 0.36-0.77). The pooled proportion of cardiac events in elderly patients treated with trastuzumab was 5% (95% CI, 4-7%). The use of trastuzumab should be considered as a standard of care in the adjuvant therapy of elderly patients with HER-2 positive breast cancer. Acute and chronic medical conditions, nutritional status and level of daily activities should be considered. Uncertainty about cardiac safety in the elderly is a major concern., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Our purpose was to evaluate the locoregional recurrence (LRR) of patients with false-negative, frozen-section or close margins of retroareolar specimen in nipple-sparing mastectomy (NSM) procedure., Methods: From 2002-2008, we recruited patients who had atypia or presence of cancer cells in definitive histology of retroareolar tissue despite of absence of tumor cell in intraoperative retroareolar frozen section. We also included the close margin cases defined as the presence of tumor cells at the first frozen section, but after deeper core out of retroareolar tissue were revealed free of malignancy. The incidence of LRR and NAC recurrence were reported, and the factors associated were analyzed., Results: Of 948 NSM procedures, there were 88 false-negative, frozen-sections and 10 close margin cases. The 5-year cumulative incidence of LRR and NAC recurrence was 11.2 % (10/98 patients) and 2.4 % (2/98 patients), respectively. Analyzing the definitive results of retroareolar tissue, the 5-year cumulative incidence of LRR was 42.9 % (n = 4) for atypia, 10 % (n = 2) for lobular carcinoma in situ (LCIS), 10 % (n = 1) for close margins, 8.7 % (n = 3) for ductal carcinoma in situ (DCIS), and 0 % for invasive carcinoma. In situ carcinoma as a primary tumor was a significant predictor of NAC recurrence (P < 0.01)., Conclusions: Despite a high reliability of frozen section, there is still a minority of false-negative results. Nevertheless, the LRR is considerably low. This fact suggests the possibility of preservation of the NAC after discussion with the patient.

Objective: The use of the left internal thoracic artery in coronary artery bypass surgery is currently recognized as the best option, providing lesser incidence of cardiovascular events and superior long-term survival. As a result, great expansion of bilateral internal thoracic artery (ITAs) grafts has been observed, with additional demonstration of improved long-term survival. Therefore the aim of this study was to examine and compare the histomorphometric structure among different segments of the left and right ITA., Method: Specimens of ITAs harvested from 18 cadavers were divided in nine proportional segments. Cuts of each segment had been stained with hematoxylin-eosin and Verhoeff-Van Gieson technique. The following parameters had been analyzed: perimeter of the arterial lumen, thickness of the intima, thickness of the media layer and amount of elastic fiber in the media layer., Results: The perimeter of both ATIs decreases downstream its course, the proximal segments of the right ITA exhibit perimeter significantly greater than left ITA The analysis of the intima thickness revealed no significant difference between left and right ITA, except in the segment 9. The thickness of media layer showed no statistical difference between them, except in the segment 1. The number of elastic layers in the distal left ITA segments is significantly higher than right ITA., Conclusion: Data analyses from this study suggest structural differences between the left and right internal thoracic arteries.