Akiyama Azusa, Minaguchi Takeo, Fujieda Kaoru, Hosokawa Yoshihiko, Nishida Keiko, Shikama Ayumi, Tasaka Nobutaka, Sakurai Manabu, Ochi Hiroyuki, Satoh Toyomi
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Oncol Lett. 2019 Dec;18(6):5952-5958. doi: 10.3892/ol.2019.10940. Epub 2019 Sep 30.
Type II endometrial carcinoma mainly originates from p53 aberration. However, the detailed prognostic significance of p53 aberration in endometrial carcinoma remains to be clarified. In the present study, abnormal p53 accumulation was analyzed using immunohistochemical techniques in endometrial carcinoma samples derived from 221 consecutive patients. The expression levels of p53 were associated with clinicopathological parameters and patient survival. P53 overexpression was observed in 37/221 patients (17%), and was associated with non-endometrioid histology, post-menopause and advanced tumor stage (III/IV; P=0.0006, P=0.03 and P=0.025, respectively). Survival analysis indicated that patients with p53-overexpressing tumors exhibited poor overall survival (OS) compared with patients without p53 overexpression (P<0.000001). Univariate and multivariate analyses demonstrated that the parameters p53 overexpression, age ≥70, non-endometrioid histology and advanced stage were significant and independent prognostic factors for poor OS (P=0.00012, P=0.00048, P=0.0027 and P=0.0015, respectively). Additionally, adjuvant radiotherapy was associated with increased OS in patients without p53 overexpression. This finding was not observed for patients with adjuvant chemotherapy. In contrast to patients without p53 overexpression, patients with p53 overexpression exhibited no association with OS (P=0.02 vs. P=0.40). Notably, adjuvant radiotherapy was identified to be a significant prognostic factor for favorable OS in the subset of patients that did not exhibit p53 overexpression and received post-operative treatment (P=0.026). The findings suggested that abnormal p53 accumulation may influence patient survival via unfavorable biological tumor properties, including rapid progression and radioresistance. The present study offered valuable insights for the genome-directed management of endometrial carcinoma.
II型子宫内膜癌主要起源于p53畸变。然而，p53畸变在子宫内膜癌中的详细预后意义仍有待阐明。在本研究中，采用免疫组织化学技术分析了221例连续患者的子宫内膜癌样本中p53的异常积累情况。p53的表达水平与临床病理参数及患者生存率相关。在221例患者中有37例（17%）观察到p53过表达，其与非子宫内膜样组织学、绝经后及肿瘤晚期（III/IV期；分别为P = 0.0006、P = 0.03和P = 0.025）相关。生存分析表明，与无p53过表达的患者相比，p53过表达肿瘤患者的总生存期（OS）较差（P < 0.000001）。单因素和多因素分析表明，p53过表达、年龄≥70岁、非子宫内膜样组织学和晚期是OS不良的显著且独立的预后因素（分别为P = 0.00012、P = 0.00048、P = 0.0027和P = 0.0015）。此外，辅助放疗与无p53过表达患者的OS增加相关。辅助化疗患者未观察到这一结果。与无p53过表达的患者相反，p53过表达患者与OS无关联（P = 0.02对P = 0.40）。值得注意的是，辅助放疗被确定为未表现出p53过表达且接受术后治疗的患者亚组中OS良好的显著预后因素（P = 0.026）。这些发现提示p53异常积累可能通过包括快速进展和放射抗性在内的不良肿瘤生物学特性影响患者生存。本研究为子宫内膜癌的基因组导向管理提供了有价值的见解。
