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[子宫内膜癌不同分子亚型中淋巴管间隙浸润的临床意义]

[Clinical significance of lympho-vascular space invasion in different molecular subtypes of endometrial carcinoma].

作者信息

Li Y M, Zhai Z Y, Li H, Li L W, Shen Z H, Zhang X B, Wang Z Q, Wang J L

机构信息

Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China.

Department of Pathology, Peking University People's Hospital, Beijing 100044, China.

出版信息

Zhonghua Fu Chan Ke Za Zhi. 2024 Aug 25;59(8):617-627. doi: 10.3760/cma.j.cn112141-20240529-00307.

Abstract

To analyze the lympho-vascular space invasion (LVSI) in different molecular subtypes of the cancer genome atlas (TCGA) molecular subtypes of endometrial cancer (EC) and to evaluate the prognostic value of LVSI in EC patients with different molecular subtypes. A total of 258 patients diagnosed EC undergoing surgery in Peking University People's Hospital from January 2016 to June 2022 were analyzed retrospectively. Among 258 patients, 14 cases were classified as POLE-ultramutated subtype, 43 as high-microsatellite instability (MSI-H) subtype, 155 as copy-number low (CNL) subtype, and 46 as copy-number high (CNH) subtype. Fifty-four patients were positive for LVSI, while 203 tested negative. (1) The incidence of LVSI was found to be highest in the CNH subtype (32.6%,15/46), followed by the MSI-H subtype (27.9%, 12/43), the CNL subtype (16.9%, 26/154), and the POLE-ultramutated subtype (1/14), with statistically significant differences (=7.79, =0.044). (2) Staging and deep myometrial invasion were higher in the LVSI positive group than those in the LVSI negative group (all <0.05), except for the POLE-ultramutated subtype. The grade, lymph node metastasis, and the expression of nuclear antigen associated with cell proliferation (Ki-67) were significantly higher in LVSI positive patients than those in LVSI negative EC patients with both MSI-H and CNL subtypes (all <0.05). In CNL subtypes patients, LVSI was also associated with age, histology subtype,and progesterone receptor (PR; all <0.05). (3) Of the 257 EC patients, 25 cases recurred during the follow-up period, with a recurrence rate of 9.7% (25/257); among them, the recurrence rate of LVSI positive patients was 22.2% (12/54), which was significantly higher than those with LVSI negative (6.4%, 13/203; =12.15, <0.001). During the follow-up period, none of the 14 patients with POLE-ultramutated had recurrence; among CNL patients, the recurrence rate was 19.2% (5/26) in LVSI positive patients, which was significantly higher than that in LVSI negative ones (5.5%, 7/128; =3.94, =0.047); where as no difference were found in both MSI-H [recurrence rates in LVSI positive and negative patients were 2/12 and 9.7% (3/31), respectively] and CNH subtype [recurrence rates between LVSI positive and negative patients were 5/15 and 9.7% (3/31), respectively] EC patients (both >0.05). After log-rank test, the 3-year recurrence free survival (RFS) rate were significantly lower in LVSI positive patients from CNL subtype and CNH subtype than those in LVSI negative patients (CNL: 80.8% vs 94.5%; CNH: 66.7% vs 90.3%; both <0.05). (4) Lymph node metastasis (=6.93, 95%: 1.15-41.65; =0.034) had a significant effect on the 3-year RFS rate of EC patients with MSI-H subtype. Multivariate analysis revealed that PR expression (=0.04, 95%: 0.01-0.14;<0.001) was significantly associated with the 3-year RFS rate of CNL subtype patients. LVSI has the highest positivity rate in CNH subtype, followed by MSI-H subtype, CNL subtype, and the lowest positivity rate in POLE-ultramutated subtype. LVSI is significantly associated with poor prognosis in CNL subtype patients and may affect the prognosis of CNH subtype patients. However, LVSI is not an independent risk factor for recurrence across all four TCGA molecular subtypes.

摘要

分析癌症基因组图谱(TCGA)子宫内膜癌(EC)分子亚型中的淋巴管间隙浸润(LVSI)情况,并评估LVSI在不同分子亚型EC患者中的预后价值。回顾性分析了2016年1月至2022年6月在北京大学人民医院接受手术的258例确诊为EC的患者。在258例患者中,14例被分类为POLE超突变亚型,43例为高微卫星不稳定(MSI-H)亚型,155例为拷贝数低(CNL)亚型,46例为拷贝数高(CNH)亚型。54例患者LVSI阳性,203例检测为阴性。(1)发现LVSI发生率在CNH亚型中最高(32.6%,15/46),其次是MSI-H亚型(27.9%,12/43)、CNL亚型(16.9%,26/154)和POLE超突变亚型(1/14),差异有统计学意义(=7.79,=0.044)。(2)除POLE超突变亚型外,LVSI阳性组的分期和肌层深层浸润高于LVSI阴性组(均<0.05)。在MSI-H和CNL亚型中,LVSI阳性患者的分级、淋巴结转移以及与细胞增殖相关的核抗原(Ki-67)表达均显著高于LVSI阴性的EC患者(均<0.05)。在CNL亚型患者中,LVSI还与年龄、组织学亚型和孕激素受体(PR;均<0.05)相关。(3)在257例EC患者中,25例在随访期间复发,复发率为9.7%(25/257);其中,LVSI阳性患者的复发率为22.2%(12/54),显著高于LVSI阴性患者(6.4%,13/203;=12.15,<0.001)。在随访期间,14例POLE超突变患者均无复发;在CNL患者中,LVSI阳性患者的复发率为19.2%(5/26),显著高于LVSI阴性患者(5.5%,7/128;=3.94,=0.047);而在MSI-H [LVSI阳性和阴性患者的复发率分别为2/12和9.7%(3/31)]和CNH亚型[LVSI阳性和阴性患者的复发率分别为5/15和9.7%(3/31)]的EC患者中均未发现差异(均>0.05)。经对数秩检验,CNL亚型和CNH亚型中LVSI阳性患者的3年无复发生存(RFS)率显著低于LVSI阴性患者(CNL:80.8%对94.5%;CNH:66.7%对90.3%;均<0.05)。(4)淋巴结转移(=6.93,95%:1.15 - 41.65;=0.034)对MSI-H亚型EC患者的3年RFS率有显著影响。多因素分析显示,PR表达(=0.04,95%:0.01 - 0.14;<0.001)与CNL亚型患者的3年RFS率显著相关。LVSI在CNH亚型中的阳性率最高,其次是MSI-H亚型、CNL亚型,在POLE超突变亚型中的阳性率最低。LVSI与CNL亚型患者的预后不良显著相关,可能影响CNH亚型患者的预后。然而,LVSI并非所有四种TCGA分子亚型复发的独立危险因素。

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