Perfil da expressão imunoistoquímica de HER-2, NF-kB e IKK em câncer de colo uterino tratado com radioterapia / Immunohistochemical expression of HER-2, NF-B and IKK in patients with cervical cancer treated with radiation therapy

INTRODUÇÃO: O tratamento padrão do câncer do colo uterino é a histerectomia radical para doença inicial e quimio-radioterapia para doença avançada. A radioterapia após a histerectomia radical tem impacto em ganho de sobrevida caso hajam fatores de risco histopatológicos para recidiva. Portanto, a busca de marcadores preditores de radiossensibilidade torna-se importante para a individualização do planejamento terapêutico. O HER-2/ErbB-2 faz parte da família de proteínas ErbB que formam um grupo de receptores de membrana e tem um papel crítico no controle de diversas funções celulares básicas como diferenciação, proliferação, migração e sobrevida celular. A ação do NF-B na carcinogênese pode ocorrer através da regulação da apoptose e controle do ciclo celular. Para ativação do NF-B é necessário a enzima quinase IKK e a atividade do NF-B foi relacionada com resistência tumoral a quimioterapia e radioterapia. A via PI3K/Akt mediada pela hiperexpressão de HER-2 pode estar envolvida na ativação do NF-B. Os objetivos foram: a) avaliar os padrões de expressão imunoistoquímica de HER-2, NF-B-p65, NF-B-p50 e IKK em pacientes portadores de câncer do colo uterino submetidos à radioterapia; b) avaliar o status do gene HER2 através de FISH; c) avaliar o papel da expressão imunoistoquímica de NF-B-p65, NF-B-p50, IKK e HER-2 como fator prognóstico para sobrevida livre de doença e sobrevida global. MATERIAIS E MÉTODOS: Trata-se de estudo retrospectivo que avaliou uma série de 32 pacientes portadores de câncer do colo do útero submetidos a tratamento com radioterapia seguido de histerectomia no período de janeiro de 1992 a junho de 2001. RESULTADOS: A idade mediana foi 45 anos (22-67). Um paciente apresentava-se no estádio IB2 (FIGO) e 31 (96,9%) estádio IIB. Todos os pacientes foram submetidos à teleterapia e braquiterapia com alta taxa de dose com caráter neoadjuvante à histerectomia radical (HR). Dezesseis (50%) pacientes apresentaram doença residual após radioterapia...

INTRODUCTION: The standard treatment of early cervical cancer is radical hysterectomy and concomitant radiation therapy and chemotherapy for advanced stages. After radical hysterectomy, adjuvant radiation therapy is indicated if risk factors are present. HER-2 is part of protein membrane family that has a critical role in cellular differentiation, proliferation and survival. The NF-B regulates apoptosis, cellular cycle, adhesion and cellular migration. NF-B is activated by IKK kinase. NF-B activation is related to resistance to radiotherapy and chemotherapy. The overexpression of HER-2 may activate the NF-B pathway through PI3K/Akt. Our aims were: a) analyze the immunohistochemical expression of HER-2, NF-B-p50, NF-B-p65 and IKK in patients with cervical cancer treated with radiation therapy followed by radical hysterectomy; b) analyze the HER-2 amplification gene with FISH; c) evaluate the immunohistochemical expression of HER-2, NF-B-p50, NF- B-p65 and IKK as a prognostic factor to recurrence and death. MATERIALS AND METHODS: A retrospective analysis was carries out on 32 patients with cervical cancer submitted to radical hysterectomy after neoadjuvant radiotherapy from January 1992 to June 2001. RESULTS: The median age was 45 years (22-67). One patient was stage IB2 (FIGO) and 31 IIB (96,9%). All patients received external beam radiotherapy and high dose vaginal brachytherapy. Sixteen (50%) patients had residual pathological disease after radical hysterectomy. Median follow-up time was 73.5 months and overall 5-year survival was 66.5%. Immunohistochemical cytoplasmic expression of NF-B-p65 e NF-B-p50 before radiotherapy was found in respectively 90.6% and 96.9% of cases. Immunohistochemical nuclear expression of NF-B-p65 and NF-B-p50 before radiotherapy was found in both 59.4% of cases. Immunohistochemical cytoplasmic expression of NF-B-p65 and NF-B-p50 in the residual tumors after radiotherapy was found in both 50% of cases. Immunohistochemical...

Reconstruction of Urinary and Gastrointestinal Tracts in Patients Submitted to Pelvic Exenteration and Sphincter Preservation

Background and Objective: Reports in the literature regarding reconstruction of the lower urinary tract with orthotopic ilealneobladder post radical cystectomy for either non-transitional cell bladder tumors or other pelvic malignancies are rare. In suchcases, the reconstruction with orthotopic neobladder may represent a technical and therapeutic challenge, especially due topatients’ previous treatments like radiotherapy. To evaluate the feasibility and oncological results of the reconstruction ofurinary and gastrointestinal tracts in patients submitted to pelvic exenteration. Methods: From April 1995 to January 2004, 13patients with pelvic malignancies and non-transitional cell bladder tumors were submitted to pelvic exenteration. Bladderreconstruction was accomplished through orthotopic ileal neobladder in all cases. Seven patients had total pelvic exenterationwith anal sphincter-sparing procedure done as well as double-stapled colorectal anastomosis. Results: The mean age was 50years. In 6 patients late complications, such as hydronephrosis and urinary infection, were observed. No patient presented daytimeurinary incontinence after 6 months. During the follow-up period, no urethral recurrences were noted and all patientsremained with their functional neobladders. Two patients died of treatment-related causes and three died of cancer; sevenpatients are alive with no evidence of disease and one is alive with cancer. Overall and cancer-specific survival at 24 and 60months was 77.0% and 57%, respectively, and the mean of follow-up was 47% months (median 43 month). Conclusions:Urinary sphincter preservation and bladder reconstruction with orthotopic ileal neobladder with or without concomitant fecalsphincter preservation is a valuable option in patients with non-transitional cell bladder tumors or other pelvic malignancies thatrequire radical cystectomy for curative purposes.