Kiemen Ashley L, Young Eric D, Blackford Amanda L, Wu Pengfei, Burkhart Richard A, Burns William R, Cameron John L, Lafaro Kelly, Shubert Christopher, Gaillard Zoe, Ebong Uwakmfon-Abasi, Reucroft Ian, Shen Yu, Dequiedt Lucie, Matos Valentina, Klöppel Günter, Kasajima Atsuko, He Jin, Hruban Ralph H
Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Carnegie 415, 600 North Wolfe Street, Baltimore, MD, USA.
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Endocr Pathol. 2025 Jun 27;36(1):24. doi: 10.1007/s12022-025-09866-z.
The clinical behavior of well-differentiated pancreatic neuroendocrine tumors (PanNETs) is difficult to predict. In order to define, more accurately, prognosticators for patients with a surgically resected PanNET, the pathologic features and Ki-67 immunolabeling indexes of PanNETs resected from 904 consecutive patients at an academic tertiary care hospital were correlated with patient outcome. The mean patient age at surgery was 56.6 years (SD 14.0), 477 were male (52.8%), and 7882 person-years of follow-up were obtained (mean 8.8 years, SD 6.5). The 10-year survival was 81% (95% CI: 77,86%) for patients with G1 PanNETs (Ki-67 <3%), 68% (95% CI: 61,76%) for patients with G2a PanNETs (Ki-67 3 - <10%), 44% (95% CI: 29,66%) for patients with G2b PanNETs (Ki-67 of 10%- ≤20%), and 23% (95% CI: 8,61%) for patients with G3 PanNETs. Vascular invasion (HR 3.0, p <0.0001), tumor size ≥ 2 cm (HR 2.88, p <0.0001), perineural invasion (HR 2.42, p<0.0001), and positive margins (HR 2.18, p <0.0001) were associated with worse overall survival. Insulinoma (HR 0.34, p=3e-04), sclerosing variant (HR 0.47, p=0.05), and cystic variant (HR 0.61, p=0.05) were associated with improved overall survival. T, N and M stages were all statistically significant classifiers of overall survival. Similar associations were found with respect to disease relapse. There was a significant (P<0.001) increase in the proportion of patients diagnosed with stage I vs stage IV disease over time. This study supports the classification of PanNETs into four grades (G1, G2a, G2b, and G3) based on Ki-67 labeling, which allows a more accurate prognostic assessments of patients.
高分化胰腺神经内分泌肿瘤（PanNETs）的临床行为难以预测。为了更准确地确定接受手术切除的PanNETs患者的预后因素，在一家学术性三级护理医院，对连续904例患者切除的PanNETs的病理特征和Ki-67免疫标记指数与患者预后进行了相关性分析。手术时患者的平均年龄为56.6岁（标准差14.0），男性477例（52.8%），获得7882人年的随访（平均8.8年，标准差6.5）。G1级PanNETs（Ki-67<3%）患者的10年生存率为81%（95%CI：77,86%），G2a级PanNETs（Ki-67 3 - <10%）患者为68%（95%CI：61,76%），G2b级PanNETs（Ki-67为10%-≤20%）患者为44%（95%CI：29,66%），G3级PanNETs患者为23%（95%CI：8,61%）。血管侵犯（HR 3.0，p<0.0001）、肿瘤大小≥2 cm（HR 2.88，p<0.0001）、神经周围侵犯（HR 2.42，p<0.0001）和切缘阳性（HR 2.18，p<0.0001）与较差的总生存期相关。胰岛素瘤（HR 0.34，p = 3e-04）、硬化型变异（HR 0.47，p = 0.05）和囊性变异（HR 0.61，p = 0.05）与总生存期改善相关。T、N和M分期均为总生存期的统计学显著分类指标。在疾病复发方面也发现了类似的关联。随着时间的推移，诊断为I期与IV期疾病的患者比例有显著（P<0.001）增加。本研究支持根据Ki-67标记将PanNETs分为四个等级（G1、G2a、G2b和G3），这有助于对患者进行更准确的预后评估。
