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鼻腔鼻窦黏膜黑色素瘤:肿瘤增殖指数和病理因素在生存中的作用

英文原题:Sinonasal Mucosal Melanoma: Role of Tumor Proliferative Indices and Pathological Factors in Survival.

查看英文原题

Sinonasal Mucosal Melanoma: Role of Tumor Proliferative Indices and Pathological Factors in Survival.

PubMed 2022/06/06(内容时间) Laryngoscope Q2 · IF 2(JCR 2025)

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研究概要

在 SNMM 患者中,Ki67、核分裂率和活跃 TILs 等病理和增殖标志物与生存相关,可考虑纳入未来的分期系统。对免疫治疗的临床反应似乎与 Ki67 指数相关。鉴于 SNMM 独特的基因谱,针对 MAPK 激酶通路的靶向治疗效用有限。证据等级:3 Laryngoscope, 132:2350-2358, 2022。

研究思路结论见上方概要

本研究的目的是确定增殖指数和病理生物标志物与鼻腔鼻窦黏膜黑色素瘤(SNMM)患者总生存期及无复发/转移生存期(OS 和 RMFS)的关联,并评估 SNMM 的基因突变图谱。

这是一项回顾性队列研究,纳入45例未接受新辅助治疗的SNMM患者,这些患者接受了以治愈为目的的手术治疗,并有可用于组织病理学复查、分子分析和基因突变评估的肿瘤组织。评估了OS和RMFS与众多肿瘤及患者相关因素的关联。

在增殖指数中,较高的Ki67和有丝分裂率与较差的OS和RMFS相关(Ki67:p = 0.0007和p < 0.0001;有丝分裂率:分别为p = 0.005和p = 0.0009)。存在大量TIL(肿瘤浸润淋巴细胞)(TILs)与改善的RMFS相关(p = 0.007),而存在淋巴血管侵犯与较差的OS和RMFS相关(分别为p = 0.02和p = 0.04)。无色素性肿瘤患者更可能有较高的T分期(p = 0.046),较不可能有大量TILs(p = 0.02),并且RMFS较差(p = 0.03)。接受免疫治疗且肿瘤Ki67 < 40%的患者相比Ki67指数更高的患者有更好的3年OS(p = 0.004)。可操作的基因突变如BRAF V600E罕见,仅在20名受检患者中的1名中存在。

展开英文摘要原文

The objective of this study is to determine the association of proliferation indices and pathologic biomarkers on overall and recurrence/metastasis-free survival (OS and RMFS) in patients with sinonasal mucosal melanoma (SNMM) and to assess the genetic mutational landscape of SNMM.

This is a retrospective cohort study of 45 SNMM patients without neoadjuvant therapy who underwent surgical therapy with curative intent and had tumor tissue available for histopathologic review, molecular analysis, and genetic mutational assessment. The OS and RMFS were assessed for associations with numerous tumor and patient-related factors.

Among proliferative indices, higher Ki67 and mitotic rates were associated with worsened OS and RMFS (Ki67: p = 0.0007 and p < 0.0001; mitotic rate: p = 0.005 and p = 0.0009, respectively). The presence of brisk tumor-infiltrating lymphocytes (TILs) was associated with improved RMFS (p = 0.007) and the presence of lymphovascular invasion was associated with worsened OS and RMFS (p = 0.02 and p = 0.04, respectively). Patients with amelanotic tumors were more likely to have higher T-stage (p = 0.046), less likely to have brisk TILs (p = 0.02) and had worsened RMFS (p = 0.03). Patients on immunotherapy with tumor Ki67 < 40% had better 3-year OS compared to those with higher Ki67 index (p = 0.004). Actionable genetic mutations such as BRAF V600E are rare and present in only 1 of 20 patients tested.

In SNMM patients, pathologic and proliferation markers such as Ki67, mitotic rate and brisk TILs are associated with survival and may be considered in future staging systems. Clinical response to immunotherapy appears to correlate with the Ki67 index. Given the distinct genetic profile of SNMM, targeted therapies against the MAPK kinase pathway have limited utility. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:2350-2358, 2022.

论文信息

作者
Guo R、Jenkins SM、Johnson BJ、Reed K、Kroneman T、Choby G
第一作者单位
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.United States
通讯作者单位
Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota, USA.United States
期刊
The Laryngoscope2022 Dec
原文标识
PubMed 35661370 · DOI 10.1002/lary.30240