在子宫内膜癌的4个分子亚群中,p53异常(拷贝数高)亚组的预后最差;然而,此亚组的组织学特征尚不明确.此外,低度肿瘤是否可以属于p53异常分子亚组,如果是,p53突变的分子亚组在低度肿瘤中的预后意义是什么.在目前的研究中,我们纳入了146例p53突变的子宫内膜癌,并基于p53和MMR蛋白表达的免疫组织化学研究和POLE突变检测(81例)或基于阵列和测序技术(65例)进行了分子亚组.我们排除了属于POLE突变体或MSI分子亚组的病例,仅研究了p53异常(分子亚组)子宫内膜癌(125例)。在71个案例中,通过免疫组织化学研究和POLE突变测试相结合来确定分子亚组,54例采用基于阵列和基于测序的方法。我们回顾了1至2个代表性的数字幻灯片从每个案例和记录的形态学特征以及临床,治疗,和生存随访数据。总的来说,子宫内膜样癌47例,55浆液性癌,和其他23种组织学类型。8例为FIGO1,21例为FIGO2,91例为FIGO3。大部分病例(24.2%)在组织学上被分类为低级别(FIGO1或2)子宫内膜样癌。没有显示预后意义的形态学特征。不同组织型之间的生存率差异无统计学意义(P=0.60)。低度子宫内膜样(FIGO1或2)与高级别(FIGO3)肿瘤的生存率没有显着差异(P=0.98)。早期阶段(阶段I),与早期相比,低度肿瘤没有显著的生存优势,高级别肿瘤(P=0.16),这在FIGO2肿瘤中更为明显。虽然没有统计学意义,FIGO2肿瘤的生存率比FIGO3肿瘤低。在有治疗数据的病例中,更多早期高级别肿瘤患者接受辅助治疗,与早期低度肿瘤患者相比,可能解释这一趋势(P=0.03)。总之,我们的研究结果表明,低级别p53异常子宫内膜样癌(尤其是FIGO2肿瘤)有一个积极的过程,预后与高级别肿瘤相似。此外,我们的研究表明,早期p53低度异常疾病的患者可能由于"低度"组织型而未得到充分治疗.
Among the 4 molecular subgroups of endometrial carcinoma, the p53 abnormal (copy number high) subgroup has the worst prognosis; however, the histologic characteristics of this subgroup are not well established. Also, it is not well established whether low-grade tumors can belong to the p53 abnormal molecular subgroup and if so, what is the prognostic significance of the p53-mutated molecular subgroup in low-grade tumors. In the current study, we included 146 p53-mutated endometrial carcinomas and performed molecular subgrouping either based on a combination of immunohistochemical studies for p53 and MMR protein expression and POLE mutation testing (81 cases) or based on array-based and sequencing-based technologies (65 cases). We excluded cases that belonged to the POLE mutant or MSI molecular subgroups and only studied p53 abnormal (molecular subgroup) endometrial carcinomas (125 cases). In 71 cases, the molecular subgroup was determined by a combination of immunohistochemical studies and POLE mutation testing, and in 54 cases by array-based and sequencing-based methods. We reviewed 1 to 2 representative digital slides from each case and recorded the morphologic characteristics as well as clinical, treatment, and survival follow-up data. Overall, 47 cases were classified as endometrioid carcinoma, 55 serous carcinoma, and 23 other histotypes. Eight cases were FIGO 1, 21 were FIGO 2, and 91 were FIGO 3. A significant proportion of the cases (24.2%) were histologically classified as low-grade (FIGO 1 or 2) endometrioid carcinoma. There was no morphologic characteristic that showed prognostic implication. There was no significant difference in survival among different histotypes (P=0.60). There was no significant difference in survival among low-grade endometrioid (FIGO 1 or 2) versus high-grade (FIGO 3) tumors (P=0.98). Early-stage (stage I), low-grade tumors showed no significant survival advantage over early-stage, high-grade tumors (P=0.16) and this was more evident in FIGO 2 tumors. Although not statistically significant, the FIGO 2 tumors showed a trend toward worse survival than FIGO 3 tumors. Among the cases with available treatment data, more patients with early-stage high-grade tumors received adjuvant treatment, compared to patients with early-stage low-grade tumors, possibly explaining this trend (P=0.03). In conclusion, the findings of our study suggest that low-grade p53 abnormal endometrioid endometrial carcinomas (especially FIGO 2 tumors) have an aggressive course, with a prognosis similar to high-grade tumors. Furthermore, our study suggests that patients who had early-stage low-grade p53 abnormal disease might have been undertreated because of the \"low-grade\" histotype.