SHEILA APARECIDA COELHO SIQUEIRA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Expression of ERCC1 protein (excision repair cross complementing group 1) in patients with invasive carcinoma of the uterine cervix (CC) undergoing definitive chemoradiation (CR)(2012) CAIRES, Inacelli Queiroz de Souza; CAIRES-LIMA, Rafael; COLOMBO, Renata; RAMOS, Clarissa C. A.; MACHADO, Karime Kalil; SIQUEIRA, Sheila Aparecida Coelho; CARVALHO, Heloisa de Andrade; FUKUSHIMA, Julia Tizue; ADRA, Thais Rodrigues; HOFF, Paulo M.; ESTEVEZ-DIZ, Maria Del PilarBackground: CC is the leading cause of cancer death among women in developing countries. ERCC1 protein participates in DNA repair through the nucleotide excision repair pathway, involved in resistance to platinum-based chemotherapy. Its value as a predictive marker of tumor response to treatment, progression or death is still unknown. We evaluated ERCC1 protein expression and clinical variables as a predictive marker of progression-free survival (PFS) and overall survival (OS) in patients (pts) with CC submitted to CR. Methods: Retrospective data analysis of pts with histological diagnosis of CC, treated with CR between 2004-2009. Platinum-based chemotherapy was administered weekly (x6) concurrent to external beam radiotherapy (EBRT) to the pelvis (39.6 – 45.0 Gy), parametrial boost (14.0 – 20.0 Gy) when indicated and high-dose rate brachytherapy (HDR) (28.0 – 30.0 Gy). ERCC1 expression was assessed by immunohistochemistry (IHC). Results: We analyzed 75 pts, median age was 55 years (range 24-76), the performance status (PS) was 0 or 1 at baseline in 50 pts (66%) and 63 had squamous histology (84%). Thirty-two were stage IIB (43%) and 19 were IIIB (25%). Sixty-five patients received cisplatin 40mg/m2/w (87%) and 9, carboplatin AUC2/w (12%), median of 6 cycles (range 2-9). Median RT and HDR doses were 59.4 Gy (range 40.4 to 60.3) and 28.0 Gy (range 14.0 – 37.5), respectively. Thirty-two pts were available by ERCC1 IHC and all expressed the marker. Median PFS and OS were 35.5 (95% CI – 13.8 - 57.6) and 81 (95% CI- 21.2 - 140.8) months, respectively. In multivariate analysis, receiving < 6 chemotherapy cycles and baseline Hb <10.0 were correlated with disease progression and death, HR 0.302; p 0.011 (95% CI- 0.012-0.762) and HR 0.6; p 0.00 (95% CI- 0.474 – 0.760), respectively. PS at baseline did not correlate with PFS or OS, HR 0.985; p 0.614 (95% CI 0.930 – 1.044). Conclusions: In this population, since all pts expressed the protein, ERCC1 expression couldn't discriminate patients who most benefit from CR. Interestingly, a minimum of 6 chemotherapy cycles and a baseline Hb ≥ 10.0 seem to have a prognostic value.conferenceObject Morphological, Immunohistochemical and Cytogenetic Bone Marrow Characterization of 12 Patients with Acquired Aplastic Anemia (AAA) That Progressed to Myelodysplastic Syndromes (MDS)(2017) MARCHESI, Raquel; VELLOSO, Elvira; GARANITO, Marlene; SIQUEIRA, Sheila; NETO, Raymundo Azevedo; KUMEDA, Cristina; ZERBINI, Maria Claudia- Quantitative analysis of lymph nodes in neck dissection specimens. Morphologic study(2016) CAPELLI, Fabio de Aquino; PAES, Vitor Ribeiro; MACHADO, Mariangela Marinheiro; MENEZES, Camila Lohmann; SILVA, Pablo Rodrigo Andrade da; SIQUEIRA, Sheila Aparecida Coelho; ALVES, Venancio Avancini Ferreira; MATOS, Leandro Luongo; CERNEA, Claudio RobertoPURPOSE: To quantify the amount of lymph nodes harvested in modified radical neck dissection. METHODS: Cross-sectional anatomical study conducted in 28 non-preserved cadavers. RESULTS: The mean number of lymph nodes found in each nodal level of the 56 modified radical neck dissections performed were: level IA - 1.5 (95% CI: 1.1 - 1.8), level IB - 2.5 (95% CI: 2.1 - 2.9), level IIA - 7.2 (95% CI: 6.0 - 8.5), IIB level - 6.5 (95% CI: 5.5 - 7.4), level III - 6.6 (95% CI: 5.7 - 7.4), level IV - 8.6 (95% CI: 7.1 - 10.1), level V - 11 (95% CI: 9.2 - 12.7), totalizing 43.8 lymph nodes (95% CI: 40.3 - 47.4). CONCLUSION: The results defined a parameter in relation to the minimum recommended nodal yield in a modified radical neck dissection, as well as the number of lymph nodes in each level of this dissection, performed in clinical practice.
- Genetic and clinical aspects of paediatric pheochromocytomas and paragangliomas(2021) PETENUCI, Janaina; GUIMARAES, Augusto G.; FAGUNDES, Gustavo F. C.; BENEDETTI, Anna Flavia F.; AFONSO, Ana Caroline F.; PEREIRA, Maria Adelaide A.; ZERBINI, Maria Claudia N.; SIQUEIRA, Sheila; YAMAUCHI, Fernando; SOARES, Silvia C.; SROUGI, Victor; TANNO, Fabio Y.; CHAMBO, Jose L.; I, Roberto Lopes; DENES, Francisco T.; HOFF, Ana O.; LATRONICO, Ana Claudia; MENDONCA, Berenice B.; V, Maria Candida B. Fragoso; ALMEIDA, Madson Q.Objective Few and conflicting reports have characterized the genetics of paediatric pheochromocytomas and paragangliomas (PPGLs). This study aimed to investigate the clinical and genetic features of Brazilian children with PPGL. Patients and Methods This study included 25 children (52% girls) with PPGL. The median age at diagnosis was 15 years (4-19). The median time of follow-up was 145 months. The genetic investigation was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification and/or target next-generation sequencing panel. Results Of the 25 children with PPGL, 11 (44%), 4 (16%), 2 (8%), 1 (4%) and 7 (28%) had germline VHL pathogenic variants, SDHB, SDHD, RET and negative genetic investigation, respectively. Children with germline VHL missense pathogenic variants were younger than those with SDHB or SDHD genetic defects [median (range), 12 (4-16) vs. 15.5 (14-19) years; P = .027]. Moreover, 10 of 11 cases with VHL pathogenic variants had bilateral pheochromocytoma (six asynchronous and four synchronous). All children with germline SDHB pathogenic variants presented with abdominal paraganglioma (one of them malignant). The two cases with SDHD pathogenic variants presented with head and neck paraganglioma. Among the cases without a genetic diagnosis, 6 and 2 had pheochromocytoma and paraganglioma, respectively. Furthermore, metastatic PPGL was diagnosed in four (16%) of 25 PPGL. Conclusions Most of the paediatric PPGL were hereditary and multifocal. The majority of the affected genes belong to pseudohypoxic cluster 1, with VHL being the most frequently mutated. Therefore, our findings impact surgical management and surveillance of children with PPGL.
conferenceObject Clinical Prognostic Models in Diffuse Large B-Cell Lymphoma Patients Are Still Essential in the Rituximab Era(2014) LAGE, Luis Alberto de Padua Covas; COSTA, Renata Oliveira; HALLACK NETO, Abrahao Elias; SIQUEIRA, Sheila; SANTUCCI, Rodrigo; PAULA, Henrique Moura de; PEREIRA, Juliana- Image-guided lymph node core needle biopsy in mycosis fungoides/Sezary syndrome: Direct comparison to surgical excision(2022) CURY-MARTINS, Jade; COUTO NETTO, Sergio Dias do; CASTRO, Stephanie Catarine Carqueijo de; SIQUEIRA, Sheila Aparecida Coelho; GIANNOTTI, Marcelo Abrantes; ZERBINI, Maria Claudia Nogueira; PEREIRA, Juliana; CULLER, Hebert; TEIXEIRA JR., Frederico Jose Ribeiro; MENEZES, Marcos Roberto de; SANCHES, Jose Antonio
- Penetrance of Functioning and Nonfunctioning Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 in the Second Decade of Life(2014) GONCALVES, Tatiana D.; TOLEDO, Rodrigo A.; SEKIYA, Tomoko; MATUGUMA, Sergio E.; MALUF FILHO, Fauze; ROCHA, Manoel S.; SIQUEIRA, Sheila A. C.; GLEZER, Andrea; BRONSTEIN, Marcelo D.; PEREIRA, Maria A. A.; JUREIDINI, Ricardo; BACCHELLA, Telesforo; MACHADO, Marcel C. C.; TOLEDO, Sergio P. A.; LOURENCO JR., Delmar M.Context: Data are scarce on the penetrance of multiple endocrine neoplasia type 1 (MEN1)-related nonfunctioning pancreatic neuroendocrine tumors (NF-PETs) and insulinomas in young MEN1 patients. Apotential positive correlation between tumor size and malignancy (2-3 cm, 18%; >3 cm, 43%) has greatly influenced the management of MEN1 adults with NF-PETs. Objective: The aim of the study was to estimate the penetrance of NF-PETs, insulinomas, and gastrinomas in young MEN1 carriers. Design: The data were obtained from a screening program (1996-2012) involving 113 MEN1 patients in a tertiary academic reference center. Patients: Nineteen MEN1 patients (aged 12-20 y; 16 patients aged 15-20 y and 3 patients aged 12-14 y) were screened for NF-PETs, insulinomas, and gastrinomas. Methods: Magnetic resonance imaging/computed tomography and endoscopic ultrasound (EUS) were performed on 10 MEN1 carriers, magnetic resonance imaging/computed tomography was performed on five patients, and four other patients underwent an EUS. Results: The overall penetrance of PETs during the second decade of life was42%(8 of 19). All eight PET patients had NF-PETs, and half of those tumors were multicentric. One-fifth of the screened patients (21%; 4 of 19) harbored at least one large tumor (>2.0 cm). Insulinoma was detected in two NF-PET patients (11%) at the initial screening; gastrinoma was not present in any cases. Six of the 11 (54%) screened patients aged 15-20 years who underwent an EUS had NF-PETs. Potential false-positive EUS results were excluded based on EUS-guided biopsy results, the reproducibility of the NF-PET findings, or the observation of increased tumor size during follow-up. Distal pancreatectomy and the nodule enucleation of pancreatic head tumors were conducted on three patients with large tumors (>2.0 cm; T2N0M0) that were classified as grade 1 neuroendocrine tumors (Ki-67 < 2%). Conclusions: Our data demonstrated high penetrance of NF-PETs in 15- to 20-year-old MEN1 patients. The high percentage of the patients presenting consensus criteria for surgery for NF-PET alone or NF-PET/insulinoma suggests a potential benefit for the periodic surveillance of these tumors in this age group.
- Differential expression of genes encoding proteins of the HGF/MET system in insulinomas(2015) MURAT, Cahue de Bernardis; ROSA, Paula Waki Lopes da; FORTES, Maria Angela Henriques Zanella; CORREA, Luciana; MACHADO, Marcel Cerqueira Cesar; NOVAK, Estela Maria; SIQUEIRA, Sheila Aparecida Coelho; PEREIRA, Maria Adelaide Albergaria; CORREA-GIANNELLA, Maria Lucia; GIANNELLA-NETO, Daniel; GIORGI, Ricardo RodriguesBackground: Insulinomas are the most common functional pancreatic neuroendocrine tumors, whereas histopathological features do not predict their biological behaviour. In an attempt to better understand the molecular processes involved in the tumorigenesis of islet beta cells, the present study evaluated the expression of genes belonging to the hepatocyte growth factor and its receptor (HGF/MET) system, namely, MET, HGF; HGFAC and ST14 (encode HGF activator and matriptase, respectively, two serine proteases that catalyze conversion of pro-HGF to active HGF); and SPINT1 and SPINT2 (encode serine peptidase inhibitors Kunitz type 1 and type 2, respectively, two inhibitors of HGF activator and of matriptase). Methods: Quantitative real-time reverse transcriptase polymerase chain reaction was employed to assess RNA expression of the target genes in 24 sporadic insulinomas: 15 grade 1 (G1), six grade 2 (G2) and three hepatic metastases. Somatic mutations of MET gene were searched by direct sequencing of exons 2, 10, 14, 16, 17 and 19. Results: Overexpression of MET was observed in the three hepatic metastases concomitantly with upregulation of the genes encoding HGF and matriptase and downregulation of SPINT1. A positive correlation was observed between MET RNA expression and Ki-67 proliferation index while a negative correlation was detected between SPINT1 expression and the mitotic index. No somatic mutations were found in MET gene. Conclusion: The final effect of the increased expression of HGF, its activator (matriptase) and its specific receptor (MET) together with a decreased expression of one potent inhibitor of matriptase (SPINT1) is probably a contribution to tumoral progression and metastatization in insulinomas.
- Development and internal validation of an adrenal cortical carcinoma prognostic score for predicting the risk of metastasis and local recurrence(2013) FREIRE, Daniel Soares; SIQUEIRA, Sheila Aparecida Coelho; ZERBINI, Maria Claudia Nogueira; WAJCHENBERG, Bernardo Leo; CORREA-GIANNELLA, Maria Lucia; LUCON, Antonio Marmo; PEREIRA, Maria Adelaide AlbergariaObjective To develop and internally validate a prognostic score to predict the risk of metastases or recurrence in patients with adrenal cortical carcinomas (ACC). Design Clinical, laboratory and pathological data from 129 ACC patients, treated in a tertiary centre, were retrospectively reviewed. Results Using a multivariate binary logistic regression analysis, we developed a prognostic score with five covariates: a functional pattern other than isolated hyperandrogenism, a tumour size >75cm, a primary tumour classified as T3/T4, the presence of microscopic venous invasion and a mitotic index >5/50 high-power fields. The prognostic score was calibrated according to the Hosmer-Lemeshow goodness-of-fit test (P=09329) and exhibited excellent overall performance (Brier score=00738). Finally, the discriminatory ability of the model, determined by the area under the ROC curve (A(ROC)), was near perfect (A(ROC), 09611; 95% CI, 092676-099552). The prediction model was internally validated with 200 bootstrap resamples and achieved excellent performance for estimating the risk of metastasis and recurrence in eight additional patients with apparently localized disease at diagnosis. Conclusion We developed and internally validated a prognostic score based on the clinicopathological data that are readily available to any attending physician. Our model can be used to accurately estimate the risk of unfavourable outcomes in ACC patients. This score could be beneficial for both patient counselling and the identification of patients in whom adjuvant mitotane is justified.
conferenceObject Metastasis of squamous cell carcinoma of the penis into a heart with pacemaker mimicking an endocardial vegetation(2013) TOMIKAWA, C.; SIQUEIRA, S. A. C.