Hubungan antara Ekspresi P53 Mutan terhadap Operabilitas Kanker Serviks Stadium IIB Pasca Kemoterapi Neoajuvan

N. Arsyad, R. Siswosudarmo, Ardhanu Kusumanto
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Abstract

Background: The therapy for stage IIB cervical cancer according to FIGO is concurrent chemoradiation. The neoadjuvant chemotherapy followed by radical hysterectomy is an alternative therapy to improve the survival rate of cancer patients. Cervical cancer is mainly caused by the infection of Human Papilloma Virus (HPV), which contains protein E6 and E7 that downregulate the apoptotic function of p53. The absent of p53 wild-type and the present of p53 mutation play roles on the cervical cancer pathogenesis. Objective: To analyze the association between the expression of mutant p53 to the stage IIB cervical cancer operability after neoadjuvant chemotherapy Method: This study was a prospective cohort, using 40 of 67 patient who met eligibility criteria. The parafin block from cervical tissue were processed for immunohistochemical staining of p53 using Anti-mutant p53 antibody [Y5] ab32049, Abcam, USA. Two study groups were assessed as: 1) weak and 2) strong expression of mutant p53 expression after neoadjuvant chemotherapy based on H-score. Both group (weak and strong) were comparable in term of mutan t p53 expression. In this study, the evaluation of operability was performed clinically. Age, BMI, histopathology, grade of differentiation, and regiment were also evaluated as the external variables. Chi square test, and logistic regression analysis were used for statistical analysis. Results and Discussion: The rate of cervical cancer operability after chemotherapy was 19 out of 40 (47.5%). The strong expression of mutant p53 was observed in 6 subjects (15%). There was no significant association between weak vs strong expression of mutant p53 to the operability of the cancer (RR 1.5, CI 95% 0.46-4.88, p 0.45). Multivariate analysis showed that combination (50 mg/m 2 dan 5 fluorourasil 450 mg/m2) was significantly correlated the operability (OR 7.02, CI 95% 1.27-40.07,  p 0.03).  Conclusion: The expression of mutant p53 not correlate with operability after neoadjuvant chemotherapy, but combination  regiment was. Keywords: expression of mutant p53, stage IIB of cervical cancer, neoadjuvant chemotherapy, operability
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在新奥乔凡化疗后,变异P53表现与宫颈癌功能之间的关系
背景:根据FIGO, IIB期宫颈癌的治疗是同步放化疗。新辅助化疗后根治性子宫切除术是提高肿瘤患者生存率的一种替代治疗方法。宫颈癌主要由人乳头瘤病毒(Human Papilloma Virus, HPV)感染引起,HPV中含有下调p53凋亡功能的蛋白E6和E7。p53野生型的缺失和p53突变的存在在宫颈癌的发病机制中发挥着重要作用。目的:分析p53突变体表达与IIB期宫颈癌新辅助化疗后可操作性的关系。方法:本研究采用前瞻性队列研究,67例患者中有40例符合入选标准。使用美国Abcam公司的抗突变型p53抗体[Y5] ab32049对宫颈组织石蜡块进行免疫组化染色。根据H-score评价两组新辅助化疗后突变型p53表达的弱表达和强表达。两组(弱组和强组)在突变t p53表达方面具有可比性。在本研究中,临床评估可操作性。年龄、体重指数、组织病理学、分化程度和团也作为外部变量进行评估。采用卡方检验和logistic回归分析进行统计分析。结果与讨论:宫颈癌化疗后的可操作性为19 / 40(47.5%)。6例(15%)患者观察到p53突变体强表达。突变型p53弱表达与强表达与肿瘤的可操作性无显著相关性(RR 1.5, CI 95% 0.46-4.88, p 0.45)。多因素分析显示,联合用药(50 mg/m2 2 / 5氟脲嘧啶450 mg/m2)可操作性显著相关(OR 7.02, CI 95% 1.27 ~ 40.07, p 0.03)。结论:p53突变体的表达与新辅助化疗后的可操作性无关,而联合化疗组与可操作性相关。关键词:突变型p53表达,宫颈癌IIB期,新辅助化疗,可操作性
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