Immunohistochemical Wwox Expression And Association With Angiogenesis, P53 Expression, Cell Proliferation And Clinicopathological Parameters In Cervical Cancer

REVISTA BRASILEIRA DE GINECOLOGIA E OBSTETRICIA(2018)

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Abstract
Objective The current study evaluated the expression of WW domain-containing oxidoreductase (WWOX), its association with clinicopathological features and with p53, Ki-67 (cell proliferation) and CD31 (angiogenesis) expression in patients with invasive cervical squamous cell carcinoma (ICSCC). To the best of our knowledge, no other study has evaluated this association.Methods Women with IB stage-ICSCC (n=20) and women with uterine leiomyoma (n=20) were prospectively evaluated. Patients with ICSCC were submitted to type B-C1 radical hysterectomy and pelvic lymphadenectomy. Patients in the control group underwent vaginal hysterectomy. Tissue samples were stained with hematoxylin and eosin for histological evaluation and protein expression was detected by immunohistochemistry studies.Results The WWOX expression was significantly lower in the tumor compared with the expression in the benign cervix (p=0.019). The WWOX expression was inversely associated with the CD31 expression in the tumor samples (p=0.018). There was no association between the WWOX expression with the p53 expression (p=0.464) or the Ki-67 expression (p=0.360) in the samples of invasive carcinoma of the cervix. There was no association between the WWOX expression and tumor size (p=0.156), grade of differentiation (p=0.914), presence of lymphatic vascular invasion (p=0.155), parametrium involvement (p=0.421) or pelvic lymph node metastasis (p=0.310) in ICSCC tissue samples.Conclusion The results suggested that WWOX may be involved in ICSCC carcinogenesis, and this marker was associated with tumor angiogenesis.ResumoObjetivo O presente estudo avaliou a expressAo do WWOX, sua associacAo com caracteristicas clinicopatologicas e com a expressAo do p53, ki-67 (proliferacAo celular) e CD31 (angiogenese) em pacientes com carcinoma invasivo de celulas escamosas do colo uterino, ou simplesmente cancer do colo uterino (CCE).Metodos Foram avaliadas prospectivamente pacientes com CCE no estagio IB ( n =20) e mulheres com mioma uterino, no grupo controle ( n =20). As pacientes com CCE foram submetidas a histerectomia radical e a linfadenectomia pelvica do tipo B-C1. As mulheres no grupo-controle foram submetidas a histerectomia vaginal. As amostras de tecido foram coradas com hematoxilina e eosina para avaliacAo histologica e a expressAo das proteinas foi detectada por imuno-histoquimico.Resultados A expressAo do WWOX foi significativamente menor no tumor quando comparada com sua expressAo no colo do utero benigno ( p =0,019). A expressAo tumoral de CD31 foi inversamente associada a expressAo de WWOX ( p =0,018). Sua expressAo nAo foi associada a expressAo tumoral de p53 e Ki-67 em pacientes com CCE ( p =0,464 e p =0,360, respectivamente). NAo houve associacAo entre a expressAo de WWOX e o tamanho do tumor ( p =0,156), grau de diferenciacAo ( p =0,914), presenca de invasAo vascular linfatica ( p =0,155), comprometimento do parametrio ( p =0,421) ou metastase dos linfonodos pelvicos ( p =0,310) em pacientes com CCE.ConclusAo Os resultados sugeriram que o WWOX pode estar envolvido na carcinogenese do CICECU e esse marcador foi associado a angiogenese tumoral.
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Key words
cervical neoplasia,immunohistochemistry,tumor suppressor gene,WWOX
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