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Gueiros L.A.,Federal University of Pernambuco | Gueiros L.A.,University of Campinas | Coletta R.D.,University of Campinas | Kowalski L.P.,AC Camargo Cancer Hospital | Lopes M.A.,University of Campinas
International Journal of Oral and Maxillofacial Surgery | Year: 2011

The aim of this study was to evaluate the clinicopathological features and immunohistochemical expression of proliferation markers in oral tongue squamous cell carcinomas (OTSCC). Sixty-three patients without previous treatment or distant metastases were selected. Clinical information was retrieved from medical charts, histopathological analysis was performed and expression of proliferation markers (Ki-67, Mcm-2 and geminin) was evaluated. Most patients were men (81%) (male:female ratio 4.25:1). The age range was 31-92 years (mean 57.6 ± 11.81 years). A high Anneroth score was associated with tumour size (p = 0.05), tumoural embolization of the blood vessels (p = 0.003), nodal metastasis (p = 0.05), nodal capsule rupture (p = 0.016) and distant metastasis (p = 0.002). Elevated Bryne scores were significantly associated with nodal capsule rupture (p = 0.02), distant metastasis (p = 0.002), shorter overall survival (OS) (p = 0.03) and disease-free survival (DFS) (p = 0.05) compared with patients with lower score. Elevated Ki-67+ cells (p = 0.05) and Mcm-2+ cells (p = 0.008) were associated with nodal metastasis and tumours with a high geminin score demonstrated a significant tendency for neural invasion (p = 0.05). Anneroth and Bryne score in association with biomarkers of proliferation can be useful for evaluating the biological behaviour of OTSCC. © 2010 International Association of Oral and Maxillofacial Surgeons.


Cunha L.L.,University of Campinas | Marcello M.A.,University of Campinas | Morari E.C.,University of Campinas | Nonogaki S.,Adolfo Lutz Institute | And 6 more authors.
Endocrine-Related Cancer | Year: 2013

B7H1 is consistently associated with inhibition of the immune system in many solid tumors. However, there is no report about its impact on differentiated thyroid carcinoma (DTC) presentation, aggressiveness, or evolution. Aiming to investigate the role of B7H1 in DTC and correlate this protein with other tumor-infiltrating immune cells, we studied 407 thyroid nodule tissue samples including 293 from DTC patients, all managed according to a same standard protocol. In addition, we obtained 5 normal and 114 benign thyroid lesions. Eighteen out of the 253 papillary thyroid carcinomas were paired with respective metastatic lymph node tissues. B7H1 (CD274) protein expression was assessed by immunohistochemistry and the gene expression was quantified by real-time PCR. Malignant tissues displayed a more intense B7H1 staining and higher mRNA levels than benign tissues (both P=0.0001). We observed a positive linear correlation between higher age at diagnosis and B7H1 mRNA levels (P<0.02896). Elevated levels of B7H1 protein were associated with the presence of CD4C, CD8C, CD20C, and FoxP3C lymphocytes (all P=0.05); tumor-associated macrophages (P=0.0001); and the presence of myeloid-derived suppressor cells (P<0.03256). Stage II-IV patients presented higher B7H1 mRNA levels than stage I cases (P<0.03522). On the contrary, a decreased expression of B7H1 protein was observed in lymph node metastasis (P<0.0152). In conclusion, our data demonstrate that B7H1 expression is associated with features of aggressiveness, suggesting that this is an immune evasion mechanism of DTC cells. © 2013 Society for Endocrinology.


Objective: To validate and assess reliability and understanding of the EORTC-C30 quality of life questionnaire and its breast cancer specific module, the EORTC-BR23. Methods: This study was conducted at the AC Camargo Cancer Hospital, São Paulo, Brazil. A total of 100 women diagnosed with breast cancer were interviewed. Internal consistency, confirmatory factorial analysis, convergent validity, construct validity and degree of understanding were examined. Reliability was assessed by comparison of means at times 1 and 2, inter-class coefficient and Bland-Altman graphics. Results: Cronbach's alpha ranged from 0.72 to 0.86 for the EORTC-C30 and from 0.78 to 0.83 for the EORTC-BR23 questionnaire. Most questions were confirmed in the confirmatory factorial analysis. In the construct validity analysis, the questionnaires were capable of differentiating patients with or without lymphedema, apart from the symptom scales of both questionnaires. Both questionnaires presented a significant correlation in most domains of the SF-36, in the convergent validity analysis. Only a few criticisms were reported concerning questions, and the mean grade of understanding was high (C30 = 4.91 and BR23 = 4.89). The questionnaires presented good rates of reliability, with the exception of the functional scale of the C30 and the symptom scale of the BR23. Conclusions: The EORTC-C30 and EORTC-BR23 quality of life questionnaires were validated, presented good rates of reliability and are easily understood, allowing them to be used in Brazil to assess quality of life among women with breast cancer.


Oliveira L.R.,University of Rio Verde | Castilho-Fernandes A.,University of Sao Paulo | Oliveira-Costa J.P.,University of Sao Paulo | Soares F.A.,Ac Camargo Cancer Hospital | And 2 more authors.
Head and Neck | Year: 2014

Background. The purpose of this study was to investigate the expression of CD44 and/or CD133 immunophenotypes and the associated effects of matrix metalloproteinase-9 (MMP-9) in early-stage oral squamous cell carcinomas (SCC) to assess their influence on tumor prognosis.Methods. The following data were derived from 150 patients: age, sex, primary anatomic site, smoking status, alcohol intake, recurrence, metastases, histological classification, treatment, disease-free survival (DFS), and overall survival (OS). Immunohistochemical study of CD44, CD133, and MMP-9 expression was performed on a tissue microarray of 150 paraffin blocks of oral SCCs.Results. The predominant immunophenotype identified to exhibit a significant correlation with MMP-9 was the CD441/CD1331. Multivariate analyses identified a significant correlation of OS with surgical treatment and with CD441/CD1331 immunophenotype.Conclusion. This investigation demonstrated the prognostic importance of CD44/CD133 expression, which can help improve the prognostic value of surgical treatment for oral SCCs when diagnosed in early stages. © 2014 Wiley Periodicals, Inc.


Quadros C.A.,Aristides Maltez Cancer Hospital | Lopes A.,Ac Camargo Cancer Hospital | Araujo I.,Aristides Maltez Cancer Hospital
Japanese Journal of Clinical Oncology | Year: 2010

Background: The good prognosis of retroperitoneal and lateral pelvic lymphadenectomy has raised the question of whether total mesorectal excision is suitable for adequate staging of rectal adenocarcinoma patients. The aims of this study were to determine the accuracy of dye and probe detection of metastatic retroperitoneal and/or lateral pelvic nodes and to define the upstaging impact of retroperitoneal and lateral pelvic lymphadenectomy in rectal adenocarcinoma patients. Methods: Ninety-seven rectal adenocarcinoma patients were submitted to total mesorectal excision and retroperitoneal and lateral pelvic lymphadenectomy. Lymphoscintigraphy using technetium-99 m-phytate and patent blue was performed to detect blue and/or radioactive retroperitoneal and/or lateral pelvic nodes which were examined histopathologically and immunohistochemically with a step-sectioning technique. Results: Mesorectal mean node count was 11.5 and retroperitoneal and/or lateral pelvic node was 11.7. Retroperitoneal and lateral pelvic lymphadenectomy identified metastases in 17.5%, upstaging 8.2%. Variables related to metastatic retroperitoneal and/or lateral pelvic nodes were the following: Stage III in total mesorectal excision specimens (P < 0.04), pT3/pT4 tumors (P = 0.047), high levels of carcinoembryonic antigen (P = 0.014) and large tumors (P = 0.03). Marker migration to retroperitoneal and/or lateral pelvic nodes occurred in 37.1%, upstaging 11.1%. The markers' accuracy in the detection of metastatic retroperitoneal and/or lateral pelvic nodes was 100%. Conclusions: Retroperitoneal and lateral pelvic lymphadenectomy detected an important rate of metastatic retroperitoneal and/or lateral pelvic nodes (RLPN), resulting in upstaging. When markers migrated, they were able to detect RLPN metastases. The use of markers should be improved in the identification of RLPN metastases for selective indication of retroperitoneal and lateral pelvic lymphadenectomy. © The Author (2010). Published by Oxford University Press. All rights reserved.


Rettori M.M.,Federal University of São Paulo | De carvalho A.C.,Federal University of São Paulo | Bomfim longo A.L.,Federal University of São Paulo | De oliveira C.Z.,Barretos Cancer Hospital | And 3 more authors.
Carcinogenesis | Year: 2013

Hypermethylation in the promoter regions of genes is associated with suppression of gene expression and has been considered a potential molecular marker for several tumor types, including head and neck squamous cell carcinomas (HNSCC). Moreover, hypermethylation can be detected in body fluids such as saliva and can be useful for the diagnosis and prognosis of patients suffering from cancer. To evaluate the hypermethylation profile as a tool for early detection of tumor recurrences, this study determines the methylation status of 24 genes in salivary rinses collected from HNSCC patients at diagnosis, just after the last curative treatment and in the patients' follow-up visit at 6 months after treatment. In the analysis of salivary rinse samples taken at diagnosis of HNSCC patients, five genes (CCNA1, DAPK, DCC, MGMT and TIMP3) showed high specificity and sensitivity. Hypermethylation in any of these five genes was correlated with the presence of tumors in the oral cavity. Patients with TIMP3 methylation in samples collected 6 months after the last curative treatment had lower local recurrence-free survival (P = 0.008). Multivariate analysis confirmed that this hypermethylation pattern remained as an independent prognostic factor for local recurrence (P = 0.025). This study presents, for the first time, the detection of TIMP3 promoter hypermethylation in post-treatment salivary rinse as an independent prognostic maker for local recurrence-free survival in patients with HNSCC, justifying the use of DNA hypermethylation detection in saliva as a tool for identifying and monitoring HNSCC patients' subgroups with high risk of developing local recurrence. © The Author 2012. Published by Oxford University Press. All rights reserved.


Perez A.A.,Federal University of Minas Gerais | Balabram D.,Federal University of Minas Gerais | Rocha R.M.,Ac Camargo Cancer Hospital | da Silva Souza A.,Federal University of Minas Gerais | Gobbi H.,Federal University of Minas Gerais
Journal of Histochemistry and Cytochemistry | Year: 2015

We assessed the co-expression of cell cycle-related biomarkers in a series of 121 consecutive cases of high-grade ductal carcinoma in situ (DCIS), pure or associated with invasive carcinoma, and their associations with the different immunoprofiles of DCIS. Cases were identified from the histopathology files of the Breast Pathology Laboratory, Federal University of Minas Gerais, Brazil, from 2003 to 2008. The expression of estrogen receptor, progesterone receptor, HER2 overexpression, cytokeratin 5, epidermal growth factor receptor 1, cyclooxygenase-2, p16 and Ki67 were assessed. Tumors were placed into five subgroups according to their immunohistochemical profile: luminal A, luminal B, HER2, basal-like and “not classified”. We found that the basal phenotype was associated with a higher frequency of p16-positive cases (83%) and the luminal A phenotype showed a higher frequency of p16-negative cases (93%; p=0.000). The association of biomarkers p16+/Ki67+/COX2+ was expressed in 02/06 cases (33.3%) of the basal phenotype but in only 01/70 cases (1.4%) of the luminal A phenotype (p=0.01). The co-expression of p16+/Ki67+/COX2- was associated with a basal phenotype (p=0.004). P16 expression, p16+/Ki67+/COX2+ and p16+/Ki67+/COX2- co-expression showed significant associations with the basal phenotype and these profiles could be used to guide more aggressive treatment strategies in patients with high-grade DCIS. © The Author(s) 2015


Destro M.F.D.S.S.,University of Campinas | Bitu C.C.,University of Campinas | Zecchin K.G.,University of Campinas | Graner E.,University of Campinas | And 3 more authors.
International Journal of Oncology | Year: 2010

A growing body of evidence has confirmed the involvement of dysregulated expression of HOX genes in cancer. HOX genes are a family of 39 transcription factors, divided in 4 clusters (HOXA to HOXD), that during normal development regulate cell proliferation and specific cell fate. In the present study it was investigated whether genes of the HOXB cluster play a role in oral cancer. We showed that most of the genes in the HOXB network are inactive in oral tissues, with exception of HOXB2, HOXB7 and HOXB13. Expression of HOXB7 was significantly higher in oral squamous cell carcinomas (OSCC) compared to normal oral mucosas. We further demonstrated that HOXB7 overexpression in HaCAT human epithelial cell line promoted proliferation, whereas downregulation of HOXB7 endogenous levels in human oral carcinoma cells (SCC9 cells) decreased proliferation. In OSCCs, expression of HOXB7 and Ki67, a marker of proliferation, correlate strongly with each other (rs=0.79, p<0.006). High immunohistochemical expression of HOXB7 was correlated with T stage (p=0.06), N stage (p=0.07), disease stage (p=0.09) and Ki67 expression (p=0.01), and patients with tumors showing high number of HOXB7-positive cells had shorter overall survival (p=0.08) and shorter disease-free survival after treatment (p=0.10) compared with patients with tumors exhibiting low amount of HOXB7-positive cells. Our data suggest that HOXB7 may contribute to oral carcinogenesis by increasing tumor cell proliferation, and imply that HOXB7 may be an important determinant of OSCC patient prognosis.


Baiocchi G.,AC Camargo Cancer Hospital | Guimaraes G.C.,AC Camargo Cancer Hospital | Rosa Oliveira R.A.,AC Camargo Cancer Hospital | Kumagai L.Y.,AC Camargo Cancer Hospital | And 5 more authors.
European Journal of Surgical Oncology | Year: 2012

Objectives: Analyze morbidity, mortality and prognostic factors after pelvic exenteration (PE) for gynecological malignancies. Methods: We reviewed a series of 107 individuals who underwent PE at A.C. Camargo Cancer Hospital from August 1982 to September 2010. Results: Median age was 56.4 years. Primary tumor sites were uterine cervix in 73 cases (68.2%); vaginal, 10 (9.3%); endometrial, 14 (13.1%); vulvar, 7 (6.5%); and uterine sarcomas, 3 (2.8%). Median tumor size was 5.5 cm. Total PE was performed in 56 cases (52.3%), anterior in 31 (29.9%), posterior in 10 (9.3%) and lateral extended in 10. Median operation time, blood transfusion and hospital stay length were 420 min (range: 180-780), 900 ml (range: 300-4500) and 13 days (range: 4-79), respectively. There was no intra-operative death. Fifty-seven (53.3%) and 48 (44.8%) patients had early and late complications, respectively. Five-year progression free survival (PFS), overall survival (OS) and cancer specific survival (CSS) were 35.8%, 27.4% and 41.1%, respectively. Endometrial cancer had better 5-year OS (64.3%) than cervical cancer (23.1%). Lymph node metastasis negatively impacted PFS, CSS and OS. Presence of perineural invasion negatively impacted PFS and CSS. No variable retained the risk of recurrence or death in the multivariate analysis. Conclusions: PE has acceptable morbidity and mortality and may be the only method that can offer long-term survival in highly selected patients. © 2012 Elsevier Ltd. All rights reserved.


Baiocchi G.,AC Camargo Cancer Hospital | Guimaraes G.C.,AC Camargo Cancer Hospital | Faloppa C.C.,AC Camargo Cancer Hospital | Kumagai L.Y.,AC Camargo Cancer Hospital | And 4 more authors.
Annals of Surgical Oncology | Year: 2013

Background: Adenocarcinoma (AC) of the cervix comprises 15-20 % of all cervical carcinomas, and data regarding the prognostic value of histologic type after pelvic exenteration (PE) are lacking. Our aim was to analyze the prognostic value of histologic type in overall survival (OS) and disease-specific survival (DSS) after PE and correlate it to clinical and pathologic variables. Methods: We reviewed a series of 77 individuals who underwent PE for cervical or vaginal cancer from January 1980 to December 2010. Results: Mean age was 54.5 years. Fifty-three patients (68.9 %) had cervical and 24 (31.1 %) vaginal cancer. Fifty-six (72.7 %) were squamous cell carcinoma (SCC) and 21 (27.3 %) ACs. We performed 42 (54.5 %) total, 18 anterior, 8 posterior, and 9 lateral extended PE. Median tumor size was 5 cm. Surgical margins were negative in 91.7 % of cases. Median operative time, length of hospital stay, and blood transfusion volume were, respectively, 420 (range 180-720) mins, 13.5 (range 4-79) days, and 900 (range 300-3900) ml. Median follow-up was 13.7 (range 1.09-114.3) months. SCC statistically correlated with presence of perineural invasion (p = 0.004). Five-year OS and DSS were, respectively, 24.4 and 37.1 %. SCC (p = 0.003) and grade 3 (p = 0.001) negatively affected OS in univariate analysis. SCC (p = 0.006), grade 3 (p = 0.003), perineural invasion (p = 0.03), lymph node metastasis (p = 0.02), and positive margins (p = 0.04) negatively affected DSS in univariate analysis. SCC and grade 3 retained the higher risk of death (OS and DSS) in multivariate analysis. Conclusions: AC histology in cervical and vaginal cancer is associated with better outcome after PE compared to SCC. © 2012 Society of Surgical Oncology.

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