Praiss Aaron M, Dagher Christian, Zhou Qin, Iasonos Alexia, Rios-Doria Eric, Abu-Rustum Nadeem R, Chiang Sarah, Momeni-Boroujeni Amir, Weigelt Britta, Ellenson Lora H, Leitao Mario M, Mueller Jennifer J
Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, New York, NY 10065, USA.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 633 3rd Avenue, New York, NY 10017, USA.
Gynecol Oncol. 2024 Dec;191:37-44. doi: 10.1016/j.ygyno.2024.09.012. Epub 2024 Sep 26.
To examine the risk of sentinel lymph node (SLN) metastases in apparent uterine-confined endometrial cancer (EC) using molecular classification with clinicopathologic features and assess oncologic outcomes by molecular subtypes with micro- or macro-metastases in SLN.
Patients undergoing surgical staging for presumed uterine-confined EC of any histology, with successful bilateral SLN mapping were included. Primary tumors were assigned molecular subtypes using a published algorithm. SLN pathology was categorized as negative, isolated tumor cells (ITCs), or micro- or macro-metastases.
Overall, 756 patients were included; 80 (10 %) had micro- or macro-metastases and 51 (7 %) had ITCs. On multivariate multinomial logistic regression, risk of micro- or macro-metastases versus negative SLN was higher for ECs with copy number-high (CN-H)/TP53abn (OR 3.1; 95 % CI 1.3-7), lymphovascular space invasion ([LVSI]; OR 8.0; 95 % CI 4-16), and deep myoinvasion (≥50 %; OR 3.33; 95 % CI 1.9-6.04). Three-year PFS rates by subtype for 68 patients with macro-metastases were 38 % (95 % CI 10-67 %) CN-low/no specific molecular subtype (CN-L/NSMP), 66 % (95 % CI 44-82 %) microsatellite instability-high (MSI-H), and 23 % (95 % CI 10-40 %) CN-H/TP53abn (p = 0.006). Three-year OS rates were 55 % (95 % CI 20-80 %) CN-L/NSMP, 83 % (95 % CI 61-93 %) MSI-H, and 55 % (95 % CI 34-71 %) CN-H/TP53abn (p = 0.048).
Integrating molecular subtype with uterine risk factors (LVSI and myoinvasion) further stratifies risk of occult SLN metastases in patients undergoing surgical staging for early-stage EC. No molecular subgroup had exceedingly low SLN metastases detected, supporting continued universal SLN assessment. Patients with macro-metastases and CN-L/NSMP or CN-H/TP53abn EC had worse outcomes than those with MSI-H EC.
利用分子分类结合临床病理特征，研究表观子宫局限性子宫内膜癌（EC）前哨淋巴结（SLN）转移的风险，并根据SLN中微转移或宏转移的分子亚型评估肿瘤学结局。
纳入因任何组织学类型的推测子宫局限性EC接受手术分期且成功进行双侧SLN定位的患者。使用已发表的算法将原发性肿瘤分为分子亚型。SLN病理分为阴性、孤立肿瘤细胞（ITC）或微转移或宏转移。
总体而言，纳入756例患者；80例（10%）有微转移或宏转移，51例（7%）有ITC。在多变量多项逻辑回归分析中，拷贝数高（CN-H）/TP53异常（CN-H/TP53abn）的EC（比值比[OR]3.1；95%置信区间[CI]1.3 - 7）、淋巴管间隙浸润（[LVSI]；OR 8.0；95% CI 4 - 16）和深部肌层浸润（≥50%；OR 3.33；95% CI 1.9 - 6.04）发生微转移或宏转移相对于SLN阴性的风险更高。68例有宏转移患者按亚型的三年无进展生存率分别为：CN低/无特定分子亚型（CN-L/NSMP）为38%（95% CI 10 - 67%）、微卫星高度不稳定（MSI-H）为66%（95% CI 44 - 82%）、CN-H/TP53abn为23%（95% CI 10 - 40%）（p = 0.006）。三年总生存率分别为：CN-L/NSMP为55%（95% CI 20 - 80%）、MSI-H为83%（95% CI 61 - 93%）、CN-H/TP53abn为55%（95% CI 34 - 71%）（p = 0.048）。
将分子亚型与子宫危险因素（LVSI和肌层浸润）相结合，可进一步对早期EC手术分期患者隐匿性SLN转移风险进行分层。没有分子亚组检测到极低的SLN转移，支持继续进行普遍的SLN评估。有宏转移且为CN-L/NSMP或CN-H/TP53abn EC的患者比MSI-H EC患者预后更差。
