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PD-L1、TIL(肿瘤浸润淋巴细胞)和 CD117 在外阴阴道黑色素瘤中的预后价值

英文原题:Prognostic value of PD-L1, tumor-infiltrating lymphocytes, and CD117 in vulvovaginal melanoma.

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Prognostic value of PD-L1, tumor-infiltrating lymphocytes, and CD117 in vulvovaginal melanoma.

PubMed 2025/06/29(内容时间) Int J Gynecol Cancer Q1 · IF 5.4(JCR 2025)

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研究概要

该研究确立 PD-L1 表达与 TIL 密度为外阴阴道黑色素瘤的独立预后因素,提示其可用于风险分层和治疗决策。

中文摘要

外阴阴道黑色素瘤是一种罕见且侵袭性强的黑色素瘤亚型,具有独特的突变模式(例如 KIT[CD117]突变频率较高),临床结局较差。本研究考察 PD-L1、TIL(肿瘤浸润淋巴细胞)及 CD117 表达对外阴阴道黑色素瘤患者预后的影响。

回顾性分析 2010 年 1 月至 2020 年 12 月经组织学确诊的外阴阴道黑色素瘤病例。采用免疫组织化学评估 PD-L1 和 CD117 表达,并依据已发表指南对 TIL 密度分级,同时评估 PD-L1 表达与主要临床病理特征的关联。主要结局为疾病特异性生存期,即从确诊至死于外阴阴道黑色素瘤的时间,采用 Kaplan-Meier 估计和 Cox 回归模型分析。

47 例患者中,70% 确诊时已为晚期(III–IV 期)。22 例(47%)检测到 PD-L1 表达,12 例(26%)存在旺盛的 TIL 浸润。PD-L1 阳性与晚期(p = .002)、TIL 浸润不旺盛或缺失(p = .003)以及淋巴血管侵犯(p = .047)相关。Kaplan-Meier 分析显示,PD-L1 阴性肿瘤患者的疾病特异性生存显著较好(3 年疾病特异性生存率:48% 对 18%,p = .008);TIL 浸润旺盛者亦显著较好(67% 对 21%,p = .003)。联合分层中,PD-L1 阴性且 TIL 浸润旺盛者预后最佳,PD-L1 阳性且 TIL 浸润不旺盛或缺失者预后最差(p < .001)。多变量分析中,PD-L1 表达(HR 1.68,95% CI 1.10–2.55,p = .015)、TIL 状态(HR 0.62,95% CI 0.43–0.89,p = .012)和疾病分期(HR 1.85,95% CI 1.22–2.81,p = .004)仍为独立预后因素。此外,30% 肿瘤(n = 14)呈 CD117 阳性,但其预后意义未能在多变量分析中保留。

研究确认 PD-L1 表达和 TIL 密度是独立预后因素,提示二者可能有助于风险分层和治疗决策。

展开英文摘要原文

Vulvovaginal melanoma represents a rare and aggressive melanoma subtype with distinct mutation patterns, such as a higher frequency of KIT (CD117) mutations, and is associated with poor clinical outcomes. This study investigated the prognostic implications of PD-L1 expression, tumor-infiltrating lymphocytes (TILs), and CD117 expression in patients with vulvovaginal melanoma.

A retrospective analysis was conducted on histologically confirmed vulvovaginal melanoma cases diagnosed between January 2010 and December 2020. Immunohistochemical evaluation was performed to assess PD-L1 and CD117 expression, while TIL density was graded using published guidelines. Associations between PD-L1 expression and key clinicopathological features were also evaluated. The primary outcome was disease-specific survival, defined as the interval from diagnosis to death specifically attributable to vulvovaginal melanoma, analyzed using Kaplan-Meier estimates and Cox regression models.

Among 47 patients, 70% presented with advanced-stage disease (stage III-IV). PD-L1 expression was detected in 22 patients (47%), and brisk TIL infiltration was observed in 12 patients (26%). PD-L1 positivity correlated with advanced disease stage (p = .002), non-brisk/absent TILs (p = .003), and lymphovascular invasion (p = .047). Kaplan-Meier analysis demonstrated significantly better disease-specific survival in PD-L1-negative tumors (3-year disease-specific survival: 48% vs 18%, p = .008) and in tumors with brisk TIL infiltration (3-year disease-specific survival: 67% vs 21%, p = .003). Combined stratification identified PD-L1-negative/brisk TIL tumors as the most favorable subgroup, while PD-L1-positive/non-brisk/absent TIL tumors exhibited the poorest prognosis (p < .001). In multivariate analysis, PD-L1 expression (HR 1.68, 95% CI 1.10 to 2.55, p = .015), TIL status (HR 0.62, 95% CI 0.43 to 0.89, p = .012), and disease stage (HR 1.85, 95% CI 1.22 to 2.81, p = .004) remained independent prognostic factors. Additionally, CD117 positivity was observed in 30% of tumors (n = 14), although its prognostic significance was not retained in multivariate analysis.

The study establishes PD-L1 expression and TIL density as independent prognostic factors in vulvovaginal melanoma, suggesting their potential utility for risk stratification and therapeutic decision-making.

论文信息

作者
Jang CS、Chuang IC
第一作者单位
Kaohsiung Veterans General Hospital, Department of Dermatology, Kaohsiung, Taiwan.Taiwan
通讯作者单位
Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Department of Anatomic Pathology, Kaohsiung, Taiwan. Electronic address: littlemummy77@gmail.com.Taiwan
期刊
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society2025 Sep
原文标识
PubMed 40782720 · DOI 10.1016/j.ijgc.2025.101996