Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
Department of Obstetrics and Gynecology, Tri-Service General Hospital, Magong City 88056, Penghu Branch, Taiwan.
Int J Environ Res Public Health. 2019 Nov 20;16(23):4589. doi: 10.3390/ijerph16234589.
Pyruvate kinase M2 (PKM2) is a regulator of the processes of glycolysis and oxidative phosphorylation, but the roles that it plays in endometrial cancer remain largely unknown. This study evaluated the PKM2 expression in normal endometrium, endometrial hyperplasia, and endometrial carcinoma, and its prognostic value was investigated in endometrial carcinoma patients.
A hospital-based retrospective review was conducted to examine the immunohistochemical PKM2 distribution in 206 endometrium samples from biopsies or hysterectomies. The immunoreactivity of PKM2 was divided into groups of low and high scores according to the extent and intensity of staining.
Intense cytoplasmic staining was observed for the PKM2 protein in malignant endometrial lesions. A high PKM2 score was observed in many endometrial carcinoma samples (50.0%), but there was a low percentage in endometrial atypical hyperplasia (12.5%). High PKM2 expression was not found in the normal endometrium (0.0%) nor endometrial hyperplasia without atypia (0.0%). The PKM2 protein score was significantly higher in endometrial carcinoma samples than premalignant endometrial lesions (p < 0.001). Notably, higher PKM2 scores in cases of endometrial carcinoma correlated with poor overall survival (p = 0.006), and the hazard ratio for death was 3.40 (95% confidence interval, 1.35-8.56).
Our results indicate that the prevalence of PKM2 tumor cells in endometrial carcinoma is significantly associated with worse prognostic factors and favors a poor prognosis. The expression of PKM2 is also a potential histopathological biomarker for use in the differential diagnosis of malignant and premalignant endometrial lesions.
丙酮酸激酶 M2(PKM2)是糖酵解和氧化磷酸化过程的调节因子,但它在子宫内膜癌中的作用在很大程度上尚不清楚。本研究评估了 PKM2 在正常子宫内膜、子宫内膜增生和子宫内膜癌中的表达,并研究了其在子宫内膜癌患者中的预后价值。
进行了一项基于医院的回顾性研究,以检查 206 例来自活检或子宫切除术的子宫内膜样本中的 PKM2 免疫组化分布。根据染色的程度和强度,将 PKM2 的免疫反应性分为低和高评分组。
恶性子宫内膜病变中观察到 PKM2 蛋白的强烈细胞质染色。许多子宫内膜癌样本中观察到高 PKM2 评分(50.0%),但子宫内膜非典型增生的比例较低(12.5%)。正常子宫内膜(0.0%)和非典型子宫内膜增生(0.0%)中均未发现 PKM2 蛋白。子宫内膜癌样本中的 PKM2 蛋白评分明显高于癌前病变(p<0.001)。值得注意的是,子宫内膜癌病例中较高的 PKM2 评分与总体生存不良相关(p=0.006),死亡的危险比为 3.40(95%置信区间,1.35-8.56)。
我们的结果表明,子宫内膜癌中 PKM2 肿瘤细胞的发生率与较差的预后因素显著相关,并预示着预后不良。PKM2 的表达也是恶性和癌前子宫内膜病变鉴别诊断的潜在组织病理学生物标志物。