Prognostic value of factors associated with hypoxia and lipid metabolism in patients with colorectal cancer

Background: Colorectal cancer (CRC) is a neoplasia with high incidence and mortality rates. It had been suggested that the inflammatory response is an important CRC prognostic factor. The disordered and accelerated proliferation of neoplastic cells decreases the oxygen and nutrient supply, generating a microenvironment characterized by hypoxia, necrosis and inflammation. This study aimed to evaluate the impact of factors associated with hypoxia, such as HIF1A (hypoxia-inducible factor 1-alpha) and VEGF (vascular endothelial growth factor), and with lipid metabolism, including PPARG (peroxisome proliferator-activated receptor-gamma), LXRA (liver X receptor-alpha) and LXRB (liver X receptor-beta), on the overall survival (OS) of CRC patients. Methods: This was a cohort study of 101 patients with high-risk stage II-III (TNM) CRC located above the peritoneal reflection. They were treated between 1990 and 2004 at the AC Camargo Cancer Center. Immunohistochemical analyses of HIF1A, VEGF, PPARG, LXRA and LXRB protein expression were performed using tissue microarrays (TMAs). Results: There was an association between the presence of vascular invasion and the lack of VEGF expression (p = 0. 028) as well as with positive HIF1A expression and lymphatic invasion (p = 0.045). The 5-year and 10-year OS rates were 76.6% and 60.2%, respectively. Patients with PPARG-positive tumors had a higher OS (p = 0.018). There were no correlations between the positive expression of VEGF, HIF1A, LXRA or LXRB and OS. The Cox regression model demonstrated that the risk of death was 2.72-fold higher in patients with PPARG-negative tumors (95% CI = 1.08­6.85). Conclusion: The PPARG expression was an independent prognostic factor for CRC tumors and might be used for risk stratification to stage II and stage III CRC patients (AU)

Avaliação da expressão imunoistoquímica de proteínas da via de sinalização mediada por TGFβ como preditores de resposta à quimioterapia pré-operatória em adultos portadores de sarcoma de partes moles de alto grau em extremidades / Protein expression evaluation of protein of genes belonging to the TGFβ pathway as predictors of response to preoperative chemotherapy with doxorubicin and ifosfamide in adult patients with high grade soft tissue sarcomas located in extremities

Introdução: Sarcomas de partes moles (SPM) constituem um grupo de neoplasias raras de comportamentos distintos. O tratamento para os tumores de alto grau, não passiveis de ressecção adequada, é feito por cirurgia, radioterapia (RT) e quimioterapia (QT). Apesar disso, 50% dos pacientes com tumores localizados ao diagnóstico morrem da doença metastática. A QT pré-operatória para o tratamento de tumores localizados, apesar de não ser considerada como padrão, é uma opção promissora. A escassez de preditores biológicos de resposta, e achados de que a superexpressão de genes pertencentes à via mediada por TGFβ estaria relacionada à resistência à QT nos levaram à tentativa de estabelecer a relação entre a expressão de FST, SMAD4, TGFβ e Id com resposta patológica. Objetivos: Avaliar por imunoistoquímica (IQ) a expressão das proteínas produzidas a partir dos genes TGFB, FST, Id1 e SMAD4 da via mediada por TGFβ, correlacionando com a resposta patológica; expandir os resultados clínicos do esquema de QT pré-operatória com doxorrubicina e ifosfamida em vigência no Hospital A.C. Camargo; determinar as taxas de toxicidade e avaliar um método de análise patológica que quantifique a percentagem de células tumorais viáveis em peça operatória. Pacientes e Métodos: 42 pacientes com SPM de alto grau localizados em extremidades, tratados com doxorrubicina e ifosfamida pré-operatória, foram observados de forma prospectiva, desde janeiro de 2005 a agosto de 2012. Amostras das biópsias e das peças operatórias foram obtidas e submetidas à pesquisa da expressão das proteínas já referidas por IQ. Resultados: A expressão das proteínas estudadas não teve correlação estatisticamente significativa com a resposta patológica...

Backgraund: Soft Tissue Sarcomas (STS) are rare neoplasms with many histological subtypes, behaviors and response to different treatments. The treatment of these tumors involves surgery, radiation and chemotherapy. Despite that 50% of patients with localized tumors will develop metastatic disease. Preoperative chemotherapy (CT) although not standard is considered a promising therapeutic option. The lack of biological predictors of response, led us to study the relationship between the expression of FST, SMAD4, TGFβ and Id (TGFβ superfamily genes) in patients submitted to preoperative CT. Objectives: To evaluate the protein expression. Produced by genes belonging to the TGFβ pathway by IH and correlate it with pathologic response; expand the preliminary results of a previous phase II trial testing a schedule of preoperative CT with doxorubicin and ifosfamide in Hospital A.C. Camargo; determine the rate of toxicity and evaluate a method of assessing pathological analysis that quantifies the percentage of viable tumor cells in surgical specimens. Patients and Methods: 42 patients with high grade STS located in extremities treated with preoperative doxorubicin and ifosfamide CT were observed prospectively, on a non controlled fashion since January 2005 to august 2012. Biopsies and surgical specimens were obtained to enable the analysis of TGFβ, FST, SMAD4 and Id protein expressional by immunohistochemistry (IH). Results: The expression of the proteins studied had no significant association with pathological response. The objective response rates of the primary tumor were 17.5% for clinical response and 15% for pathologic complete response. Only 7.5% patients had a limb amputated. The rate of surgical contraindication was 4.7%. Grade 3-4 toxicity occurred in 45.2% of cases. Conclusion: The method of pathological response analysis was considered easily applicable. TGFβ-mediated pathway proteins studied did not correlate with pathological response...