FERNANDO NALESSO AGUIAR
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Association Between GATA3 and Histopathological and Immunohistochemical Parameters in Early-Infiltrating Breast Carcinomas(2022) SOUZA, Priscila de Medeiros; CARVALHO, Filomena Marino; AGUIAR, Fernando N.; GAGLIATO, Debora; BARROS, Alfredo Carlos Simoes Dornellas deObjective: This study evaluated the frequency of GATA-binding protein 3 (GATA3) expression in early breast cancer and its relationship with histopathological and immunohistochemical parameters. Materials and Methods: GATA3 was analysed by immunohistochemistry in histological sections of rumors from 105 female patients, with histological diagnosis of invasive breast carcinoma (BC), at clinical stages I, II and IIIA, who underwent primary surgical treatment. GATA3 nuclear expression was determined as the percentage of positive tumor cells and further categorized as high (positive expression in more than 95% of cells) or non-high (negative or low positive expression in up to 95% of rumor cells). GATA3 expression was analysed according to the patient age, tumor and node pathological stage, histological type, histological and nuclear grade, lymphovascular invasion, and estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), human epidermal growth factor 2 (HERZ) status, and Ki-67 expression. Results: GATA3 expression was positive in 103 cases (98.1%). High expression was significantly associated with low histological and nuclear grade, positive hormonal receptors, and less proliferative activity based on Ki-67 expression. A prominent feature was that 94.7% of the ER-posirive/HER2-negative cases presented high-GATA3 expression, as 94.0% of the rumors showing high-GATA3 were ER-positive. In ER-negative/HER2-positive or ER-negative/HER2- negative, high-GATA3 was present in 25% while 75% were non-high-GATA3 compared with ER-positive/HER2- negative (4.1%) and ER-positive/HER2-positive (20%). Proliferative activity in triple-negative breast cancer tended to be higher among rumors with low-GKIA3, irrespective of AR expression. In the group of ER-positive/HER2-negative tumors only three cases were low-GATA3 (85% and 80%), both with high proliferative activity. Conclusion: High GATA3 expression is associated with favorable histopathologic and immunohistochemical BC prognostic factors.
- L1 Cell Adhesion Molecule (L1CAM) expression in endometrioid endometrial carcinomas: A possible pre-operative surrogate of lymph vascular space invasion(2018) FREITAS, Daniela de; AGUIAR, Fernando Nalesso; ANTON, Cristina; BACCHI, Carlos Eduardo; CARVALHO, Jesus Paula; CARVALHO, Filomena MarinoBackground Risk stratification of endometrial carcinomas is primarily based on surgical staging that requires extensive retroperitoneal lymph node dissection. One of the most powerful predictor of lymph node involvement is the lymph vascular space invasion (LVSI). The objective of this study was to determine the potential of L1 Cell Adhesion Molecule (L1CAM) to predict LVSI and its association with other risk factors in endometrioid endometrial carcinomas. Materials and methods We studied 47 consecutive patients aged 37-88 (61.34 +/- 10.52). Twenty-three patients (48.9%) were submitted to complete surgical staging. Nine patients (19.1%) underwent surgical staging without para-aortic dissection. Seven (14.9%) were submitted to hysterectomy with no lymph node dissection. Eight patients (17.0%) only had the biopsy material for analysis. The 32 patients submitted to lymphadenectomy were staged according to the FIGO system and classified among the risk categories of the ESMO-ESGO-ESTRO guidelines. The following histological characteristics were analyzed: tumor size (mm), depth of myometrial infiltration, presence of microcystic, elongated, and fragmented (MELF) pattern of myoinvasion, and lymph vascular space invasion (LVSI). Immunohistochemical analyses of mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, p53, and L1CAM were performed in formalin-fixed paraffin embedded whole tumor tissue sections. Results LVSI was identified in 26/41 (63,4%) of the cases. L1CAM was positive in 8/47 (17%) cases, all of them positive for LVSI and within the high-risk category of ESMO-ESGO-ESTRO. L1CAM-positive cases were associated with high histological grade and p53 aberrant immunohistochemical profile. Besides, it showed a trend to larger tumors, greater depth of myometrial infiltration, and with a higher frequency of the MELF pattern of myoinvasion. LVSI was also associated with FIGO stage, tumor size, depth of myometrial infiltration, and tumor grade. Conclusions L1CAM is highly associated with LVSI and could be used as a pre-operative predictor of lymph node involvement in endometrioid endometrial carcinomas.
- Pathological macroscopic evaluation of breast density versus mammographic breast density in breast cancer conserving surgery(2023) REIS, Yedda Nunes; MOTA, Bruna Salani; MOTA, Rosa Maria Salani; SHIMIZU, Carlos; RICCI, Marcos Desiderio; AGUIAR, Fernando Nalesso; SOARES-JR, Jose Maria; BARACAT, Edmund Chada; FILASSI, Jose RobertoCorrelation between imaging and anatomopathological breast density has been superficially explored and is heterogeneous in current medical literature. It is possible that mammographic and pathological findings are divergent. The aim of this study is to evaluate the association between breast density classified by mammography and breast density of pathological macroscopic examination in specimens of breast cancer conservative surgeries. Post-hoc, exploratory analysis of a prospective randomized clinical trial of patients with breast cancer candidates for breast conservative surgery. Breast mammographic density (MD) was analyzed according to ACR BI-RADS (R) criteria, and pathologic macroscopic evaluation of breast density (PMBD) was estimated by visually calculating the ratio between stromal and fatty tissue. From 412 patients, MD was A in 291 (70,6%), B in 80 (19,4%) B, C in 35 (8,5%), and D in 6 (1,5%). Ninety-nine percent (201/203) of patients classified as A+B in MD were correspondently classified in PMBD. Conversely, only 18.7% (39/209) of patients with MD C+D were classified correspondently in PMBD (p < 0.001). Binary logistic regression showed age (OR 1.06, 1.01-1.12 95% CI, p 0.013) and nulliparity (OR 0.39, 0.17-0.96 95% CI, p 0.039) as predictors of A+B PMBD.Conclusion: Mammographic and pathologic macroscopic breast density showed no association in our study for breast C or D in breast image. The fatty breast was associated with older patients and the nulliparity decreases the chance of fatty breasts nearby 60%.
- SPECT-CT-Guided Thoracoscopic Biopsy of Sentinel Lymph Nodes in the Internal Mammary Chain in Patients With Breast Cancer A Pilot Study(2016) PIATO, Jose Roberto Morales; FILASSI, Jose Roberto; VEGA, Alberto Jorge Monteiro Dela; COURA-FILHO, George Barberio; AGUIAR, Fernando Nalesso; PORCIUNCULA, Ligia Maria Teixeira Pereira; DORIA, Maira Teixeira; SOARES JR., Jose Maria; BARACAT, Edmund ChadaObjective: The objective of this study was to determine the impact of the use of single-photon emission computed tomography fused with computed tomography (SPECT-CT) on thoracoscopic biopsy of sentinel lymph nodes (SLNs) in the internal mammary chain in patients with breast cancer by evaluating resultant changes in staging and their clinical implications. Methods: Between September 2010 and January 2014, we performed lymphoscintigraphy-assisted thoracoscopic biopsy of the internal mammary chain SLN in 20 patients with breast cancer. Single-photon emission computed tomography fused with computed tomography was also used in 13 of these patients. The sentinel nodes were surgically identified with the aid of a gamma probe. Results: Sentinel lymph nodes were identified surgically in 19 of 20 patients. In the 13 patients in whom SPECT-CT was used, it readily identified SLNs, especially when they were located over an intercostal space. Change of staging occurred in three patients (15%), two of whom accordingly received adjuvant radiotherapy to the internal thoracic chain. Conclusions: Compared with lymphoscintigraphy alone, the use of SPECT-CT improves localization of the SLN in the internal mammary chain, allowing more accurate planning of each individual's treatment.
- Nipple-sparing mastectomy for early breast cancer: the importance of intraoperative evaluation of retroareolar margins and intra-nipple duct removal(2020) HEINZEN, Rebeca Neves; BARROS, Alfredo Carlos Simoes Dornellas de; CARVALHO, Filomena Marino; AGUIAR, Fernando Nalesso; NIMIR, Cristiane da Costa Bandeira Abrahao; JACOMO, Alfredo LuizBackground: Nipple-sparing mastectomy (NSM) is increasingly performed for breast cancer (BC) treatment. To ensure local control with this procedure, it is important to obtain clear surgical margins. Here, we aimed to estimate the confidence in intraoperative evaluation of the retroareolar margin (IERM) and the necessity of removing the intra-nipple ducts. Methods: In this retrospective cohort study, we evaluated 224 BC (infiltrating carcinoma 178, ductal carcinoma in situ 46) patients, who underwent NSM. IERM was determined via cytology and frozen sections. Following gland removal, the intra-nipple ducts were excised and embedded in paraffin for analysis. The retroareolar tissue was also paraffin-embedded and reanalyzed for definitive evaluation of retroareolar margins (DERM). The IERM predictive capacity in relation to DERM and the frequency of intra-nipple duct involvement were estimated. Results: IERM classified the sub-nipple areolar complex area as cancer-free in 219 cases (97.8%). The condition of clear retroareolar margin was confirmed by DERM in 216 cases (98.6%). The IERM accuracy was estimated as 98.6%. Ductal carcinoma in situ was detected in intra-nipple ducts using paraffin sections in 1.8% of the cases, despite dear IERM (4/219). Conclusions: In conclusion, IERM affords high accuracy and its results are suitable to manage the nipple-areolar complex. Nevertheless, some patients may retain residual disease in the intra-nipple ducts; thus, these ducts should ideally be removed during NSM.
- Validation of the Residual Cancer Burden Index as a prognostic tool in women with locally advanced breast cancer treated with neoadjuvant chemotherapy(2023) CUNHA, Juliana Pierobon Gomes da; GONCALVES, Rodrigo; SILVA, Fernando; AGUIAR, Fernando Nalesso; MOTA, Bruna Salani; CHEQUIM, Bruna Bello; SOARES, Jose Maria; BARACAT, Edmund C.; FILASSI, Jose RobertoAims To correlate the 'Residual Cancer Burden' (RCB) index with overall survival (OS) and disease-free survival (DFS) in women undergoing neoadjuvant chemotherapy at the Cancer Institute of the State of Sao Paulo. Methods We analysed the medical records of patients with breast cancer who underwent neoadjuvant chemotherapy and breast surgery, from 2011 to December 2017. Variables analysed were age, clinical and pathological staging, molecular subtype, number of recurrences or metastases, number of deaths, value and class of the RCB index. We used the Kaplan-Meier and the log-rank statistics to evaluate the possible association between RCB and OS and DFS. A regression model was used to determine the independent association of the RCB with the outcomes controlling for confounding factors. Results 347 patients were included in the analysis with a mean age of 49.39 years. Initial clinical staging was T3 in 57.9% of patients and 43.8% of patients had N1 axillary status. Survival analysis showed a statistically significant better prognosis for the RCB 0 (pCR) subgroup compared with RCB 1, 2 and 3 (log rank p=0.01). In a multivariate analysis, only the RCB classification showed a statistically significant correlation with DFS (RCB 1, HR 6.9, CI 1.9 to 25.4, p=0.004; RCB 2, HR 4.2, CI 1.6 to 10.8, p=0.03; and RCB 3, HR 7.6, CI 2.76 to 20.8, p=0.00). Conclusion We demonstrated a positive and significant relationship between the RCB index and the risk of relapse and death.
- Improved frozen section examination of the retroareolar margin for prediction of nipple involvement in breast cancer(2015) PIATO, J. R. Morales; AGUIAR, F. N.; MOTA, B. S.; RICCI, M. D.; DORIA, M. T.; ALVES-JALES, R. D.; MESSIAS, A. P.; FILASSI, J. R.; BARACAT, E. C.Introduction: In this prospective ex vivo study, we propose a new technique for the intraoperative examination of retroareolar tissue and describe both surgical excision and pathological methods. We performed a nipple-sparing mastectomy simulation in patients selected to total mastectomy, in order to evaluate the accuracy of these new technique. Materials and methods: A total of 158 total mastectomy specimens from patients affected by ductal carcinoma in situ (n = 15) or invasive ductal carcinoma (stages I, II, or IIIA) (n = 143) were examined. To obtain the entire sample area, the terminal retroareolar milk duct bunch was isolated. Fragments approximately 1.5 cm in length were excised and sectioned in parallel at the base of the nipple using a cold bistoury. Three transverse histological sections (4 gm each) at 200 gm intervals that included the entire isolated fragments were subjected to frozen section examination. The sections were stained with hematoxylin-eosin and were evaluated. The remainder of each fragment was embedded in paraffin and 4 gm sections were subsequently stained with hematoxylin-eosin and examined. Results: There were two false-negative (1.3%) and five false-positive (3.1%) findings among the frozen and paraffin sections analyzed. A statistical analysis of the frozen section examinations showed a sensitivity of 92.0%, a specificity of 96.2%, a positive predictive value of 82.1%, a negative predictive value of 98.4%, and an accuracy of 95.4%. Conclusion: The frozen section examination technique described here detected nipple involvement in breast cancer with greater accuracy than the frozen section usually performed by most surgeons.
- Basal cytokeratin as a potential marker of low risk of invasion in ductal carcinoma in situ(2013) AGUIAR, Fernando N.; MENDES, Henrique N.; CIRQUEIRA, Cinthya S.; BACCHI, Carlos E.; CARVALHO, Filomena M.OBJECTIVES: Biological markers that predict the development of invasive breast cancer are needed to improve personalized therapy for patients diagnosed with ductal carcinoma in situ. We investigated the role of basal cytokeratin 5/6 in the risk of invasion in breast ductal carcinoma in situ. METHODS: We constructed tissue microarrays using 236 ductal carcinoma in situ samples: 90 pure samples (group 1) and 146 samples associated with invasive carcinoma (group 2). Both groups had similar nuclear grades and were obtained from patients of similar ages. The groups were compared in terms of estrogen (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) expression, cytokeratin 5/6 immunostaining, human epidermal growth factor receptor 1 (EGFR) membrane staining and molecular subtype, as indicated by their immunohistochemistry profiles. RESULTS: ER/PR-negative status was predictive of invasion, whereas HER2 superexpression and cytokeratin 5/6-positive status were negatively associated with invasion. Among the high-grade ductal carcinoma in situ cases, a triple-positive profile (positive for estrogen receptor, progesterone receptor, and HER2) and cytokeratin 5/6 expression by neoplastic cells were negatively associated with invasion. In the low-grade ductal carcinoma in situ subgroup, only cytokeratin 5/6 expression exhibited a negative association with the probability of invasion. CONCLUSION: The immunohistochemical expression of cytokeratin 5/6 by ductal carcinoma in situ epithelial cells may provide clinically useful information regarding the risk of progression to invasive disease.
- Functional endometrial polyps in infertile asymptomatic patients: a possible evolution of vascular changes secondary to endometritis(2013) CARVALHO, Filomena Marino; AGUIAR, Fernando Nalesso; TOMIOKA, Renato; OLIVEIRA, Ricardo M. de; FRANTZ, Nibo; UENO, JojiObjective: Functional polyps and chronic endometritis are among the most common abnormalities seen in the endometrium of patients with implantation failures and recurrent miscarriages. In this study we describe morphological vascular changes in endometrial samples from asymptomatic infertile patients and their association with chronic endometritis and polyp. Study design: We selected 435 asymptomatic infertility patients submitted to office-based diagnostic hysteroscopy and endometrial biopsy. We described vascular changes and searched for histologic signs of endometritis and functional polyps in the endometrial samples. We explored the associations between these conditions. Results: Signs of endometritis, vascular changes and polyps were identified in 176 (40.5%), 168 (38.6%) and 102 (23.4%) cases, respectively. There was a significant association between endometritis and vascular changes. The more frequent vascular alteration (70%) was the hyaline thickening of vessels, a morphological pattern very similar to the thick-walled vessels of polyps. Polyps were associated with endometritis in 28 (27.4%) cases and with other vascular changes besides the vascular stalk in 14(13.7%). All the polyps with vascular changes had histologic evidence of endometritis. There was a significant association between inflammatory phenomena and vascular changes, even among cases of polyps. Conclusions: Endometrial samples from infertile patients present a broad spectrum of vascular changes, most of them associated with endometritis. This association is also identified in functional polyps. Our results suggest that these alterations may be etiologically related. It is possible that the vessel axis of functional polyps actually may originate from the evolution of the vascular changes associated with endometritis. This would place functional polyps among the spectrum of inflammatory endometrial diseases.
- Clinicopathological characteristics of endometrial carcinomas according to DNA mismatch repair protein status(2023) FREITAS, Daniela de; AGUIAR, Fernando Nalesso; ANTON, Cristina; ALMEIDA, Danielle Cristina de; BACCHI, Carlos Eduardo; CARVALHO, Jesus Paula; CARVALHO, Filomena MarinoDNA mismatch repair protein deficiency (MMRd) in endometrial carcinoma is associated with the risk of Lynch syndrome and response to immune checkpoint inhibitors. It is also related to mi-crosatellite instability and corresponds to a molecular subtype of endometrial tumor with an unclear prognosis. Here, we evaluated the clinicopathological characteristics and prognosis of 312 consecutive endometrial carcinoma cases submitted to complete surgical staging at a single institution. We compared MMRd and mismatch repair protein-proficient (MMRp) tumors and examined the effects of the MMR protein loss type (MLH1/PMS2 vs. MSH2/MSH6) and influence of L1CAM and p53 expression. The median follow-up period was 54.5 (range, 0-120.5) months. No difference was observed between MMRd [n = 166 (37.2%)] and MMRp [n = 196 (62.8%)] cases in terms of age, body mass index, FIGO stage, tumor grade, tumor size, depth of myometrial infiltration, or lymph node metastasis. More MMRd than MMRp tumors had endometrioid his-tology (87.9% vs. 75.5%) and despite MMRd had more lymphovascular space invasion (LVSI; 27.2% vs. 16.9%), they presented fewer recurrences and no difference in lymph node metastasis and disease-related death. Relative to those with MLH1/MSH6 loss, tumors with MSH2/MSH6 loss were diagnosed at earlier FIGO stages, were smaller, and had less & GE;50% myometrial inva-sion, LVSI and lymph node metastasis. Outcomes, however, did not differ between these groups. L1CAM positivity and mutation-type p53 expression were more common in MMRp than in MMRd tumors and did not differ between the MLH1/PMS2 and MSH2/MSH6 loss groups. In the entire cohort, L1CAM and mutation p53 expression were associated with worse prognosis, but only non-endometrioid histology, FIGO stage III/IV, and deep myometrial infiltration were significant predictors. In the subgroup of endometrioid carcinomas, only FIGO stage III/IV was associated with poor outcomes. The risk of lymph node metastasis was associated with tumor size, non-endometrioid histology, and multifocal LVSI. For MMRd tumors, only tumor size and myo-metrial invasion depth were predictive of lymph node involvement. In our cohort, MMRd tumors were associated with greater recurrence-free, but not overall, survival. The precise identification of MMRd status, present in a substantial proportion of endometrial cancer cases, is a challenge to be overcome for proper patient management. MMRd status serves as a marker for Lynch syndrome, and a significant number of these tumors are high risk and candidate to immunotherapy.