重新定义低级别胰腺神经内分泌肿瘤的 Ki-67 指数分层：提高其对疾病复发的预后价值。

Redefining the Ki-67 Index Stratification for Low-Grade Pancreatic Neuroendocrine Tumors: Improving Its Prognostic Value for Recurrence of Disease.

机构信息

Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.

Department of Pathology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.

出版信息

Ann Surg Oncol. 2018 Jan;25(1):290-298. doi: 10.1245/s10434-017-6140-8. Epub 2017 Oct 27.

DOI:10.1245/s10434-017-6140-8

PMID:29079920

Abstract

BACKGROUND

The Ki-67 index is an established prognostic marker for recurrence after resection of pancreatic neuroendocrine tumors (PanNETs) that groups tumors into three categories: low grade (< 3%), intermediate grade (3-20%), and high grade (> 20%). Given that the majority of resected PanNETs have a Ki-67 less than 3%, this study aimed to stratify this group further to predict disease recurrence more accurately.

METHODS

The Ki-67 index was pathologically re-reviewed and scored by a pathologist blinded to all other clinicopathologic variables using tissue microarray blocks made in triplicate. All patients who underwent curative-intent resection of non-metastatic PanNETs at a single institution from 2000 to 2013 were included in the study. The primary outcome was recurrence-free survival (RFS).

RESULTS

Of 113 patients with well-differentiated PanNETs resected, 83 had tissue available for pathologic re-review. The Ki-67 index was lower than 3% for 72 tumors (87%) and between 3 and 20% for 11 tumors (13%). Considering only Ki-67 less than 3%, the tumors were further stratified by Ki-67 into three groups: group A (< 1%, n = 43), group B (1-1.99%, n = 23), and group C (2-2.99%, n = 6). Compared with group A, groups B and C more frequently had advanced T stage (T3: 44% and 67% vs 12%; p = 0.003) and lymphovascular invasion (50% and 83% vs 23%; p = 0.007). Groups B and C had similar 1- and 3-year RFS, both less than group A. After combining groups B and C, a Ki-67 of 1-2.99% was associated with decreased RFS compared with group A (< 1%). This persisted in the multivariable analysis (hazard ratio [HR] 8.6; 95% confidence interval [CI] 1.0-70.7; p = 0.045), with control used for tumor size, margin-positivity, lymph node involvement, and advanced T stage.

CONCLUSIONS

PanNETs with a Ki-67 of 1-2.99% exhibit distinct biologic behavior and earlier disease recurrence than those with a Ki-67 lower than 1%. This new stratification scheme, if externally validated, should be incorporated into future grading systems to guide both surveillance protocols and treatment strategies.

摘要

背景

Ki-67 指数是一种已被证实的用于预测胰腺神经内分泌肿瘤（PanNETs）切除后复发的预后标志物，它将肿瘤分为三类：低级别（<3%）、中级（3-20%）和高级（>20%）。鉴于大多数切除的 PanNETs 的 Ki-67 低于 3%，本研究旨在进一步对这组患者进行分层，以更准确地预测疾病复发。

方法

通过组织微阵列块对在一家机构接受治疗性切除的非转移性 PanNETs 的患者进行病理复查和评分，这些组织微阵列块是由一位对所有其他临床病理变量均不知情的病理学家制作的，并且进行了三次重复。所有在 2000 年至 2013 年间接受根治性切除术的分化良好的 PanNETs 患者均被纳入本研究。主要结局是无复发生存率（RFS）。

结果

在 113 例分化良好的 PanNETs 患者中，有 83 例有可供病理复查的组织。72 例肿瘤（87%）的 Ki-67 指数低于 3%，11 例肿瘤（13%）的 Ki-67 指数在 3%至 20%之间。仅考虑 Ki-67 指数低于 3%，则根据 Ki-67 将肿瘤进一步分为三组：A 组（<1%，n=43）、B 组（1-1.99%，n=23）和 C 组（2-2.99%，n=6）。与 A 组相比，B 组和 C 组更常出现晚期 T 分期（T3：44%和 67% vs 12%；p=0.003）和血管淋巴管侵犯（50%和 83% vs 23%；p=0.007）。B 组和 C 组的 1 年和 3 年 RFS 相似，均低于 A 组。将 B 组和 C 组合并后，Ki-67 为 1-2.99%与 A 组（<1%）相比，RFS 降低。这在多变量分析中仍然存在（风险比[HR]8.6；95%置信区间[CI]1.0-70.7；p=0.045），使用肿瘤大小、切缘阳性、淋巴结受累和晚期 T 分期进行控制。