Objective: 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. Methods: 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. Results: (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 (χ2=7.79, P=0.044). (2) Staging and deep myometrial invasion were higher in the LVSI positive group than those in the LVSI negative group (all P<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 P<0.05). In CNL subtypes patients, LVSI was also associated with age, histology subtype,and progesterone receptor (PR; all P<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; χ2=12.15, P<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; χ2=3.94, P=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 P>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 P<0.05). (4) Lymph node metastasis (HR=6.93, 95%CI: 1.15-41.65; P=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 (HR=0.04, 95%CI: 0.01-0.14;P<0.001) was significantly associated with the 3-year RFS rate of CNL subtype patients. Conclusions: 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.
目的： 分析不同癌症基因组图谱（TCGA）分子分型子宫内膜癌（EC）中淋巴脉管间隙浸润（LVSI）的情况，并评估LVSI对不同分子分型EC患者预后的影响。 方法： 回顾性分析2016年1月—2022年6月在北京大学人民医院接受手术治疗的258例EC患者的临床病理资料。其中，TCGA分子分型为POLE超突变型14例，高度微卫星不稳定性（MSI-H）型43例，低拷贝数（CNL）型155例，高拷贝数（CNH）型46例；LVSI阳性54例，LVSI阴性203例，不详（术后失访，为CNL型）1例。 结果： （1）LVSI阳性率：不同分子分型EC患者的LVSI阳性率依次为CNH型（32.6%，15/46）、MSI-H型（27.9%，12/43）、CNL型（16.9%，26/154）、POLE超突变型（1/14），4种分子分型患者的LVSI阳性率比较，差异有统计学意义（χ2=7.79，P=0.044）。（2）临床病理资料：除POLE超突变型外，其余3种分子分型EC中LVSI阳性患者的手术病理分期、深肌层浸润比例均显著高于LVSI阴性者（P均<0.05）；在MSI-H型和CNL型EC中，LVSI阳性患者的病理分级、淋巴结转移率及细胞增殖相关核抗原（Ki-67）指数均显著高于LVSI阴性者（P均<0.05）；在CNL型EC中，LVSI状态还与患者年龄、病理类型及孕激素受体（PR）表达状态均显著有关（P均<0.05）。（3）复发率：257例EC患者（1例失访）中，随访期内复发25例，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阴性者（6.4%，13/203；χ2=12.15，P<0.001）。其中，14例POLE超突变型EC患者均无复发；CNL型EC患者中，LVSI阳性患者的复发率为19.2%（5/26），显著高于LVSI阴性者（5.5%，7/128；χ2=3.94，P=0.047）；而在MSI-H型［LVSI阳性、阴性患者的复发率分别为2/12、9.7%（3/31）］和CNH型［LVSI阳性、阴性患者的复发率分别为5/15、9.7%（3/31）］EC患者中均未发现这种差异（P均>0.05）。log-rank检验显示，CNL型和CNH型EC中LVSI阳性患者的3年无复发生存（RFS）率（分别为80.8%、66.7%）均显著低于LVSI阴性者（分别为94.5%、90.3%；P均<0.05）。（4）预后影响因素：单因素分析显示，在MSI-H型EC患者中，淋巴结转移（HR=6.93，95%CI为1.15~41.65；P=0.034）显著影响患者的3年RFS率；在CNL型EC患者中，手术病理分期、病理分级、淋巴结转移、ER表达、PR表达、p53表达、Ki-67表达、手术途径、术后辅助化疗均显著影响患者的3年RFS率（P均<0.05）。多因素分析显示，PR表达（HR=0.04，95%CI为0.01~0.14；P<0.001）为影响CNL型EC患者3年RFS率的独立危险因素。 结论： LVSI在CNH型中阳性率最高，其次为MSI-H型、CNL型，在POLE超突变型中阳性率最低。LVSI与CNL型EC患者的不良预后明显相关，与CNH型EC患者的预后可能相关。但在各分子分型EC患者中，LVSI均不是影响其复发的独立危险因素。.