CD44v6 在胃肠胰神经内分泌肿瘤中的表达：临床病理相关性与预后。

CD44v6 expression in gastroenteropancreatic neuroendocrine neoplasms: Clinicopathological correlation and prognosis.

机构信息

Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

出版信息

Pathol Res Pract. 2022 Dec;240:154213. doi: 10.1016/j.prp.2022.154213. Epub 2022 Nov 11.

DOI:10.1016/j.prp.2022.154213

PMID:36403312

Abstract

BACKGROUND

Clinical course of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) patients are determined by complicated and multifaceted factors. Ki-67 has been used to predict the behavior of NEN with statistically significant high probability. Immunohistochemical prognostic markers other than Ki-67 have been reported, but due to insufficient validation, they have not been used routinely. CD44 and its isoform variants showed significant inverse correlation with lymph node status, distant metastasis, and mortality in pancreatic neuroendocrine neoplasm (Pan-NEN). The aim of this study is to determine the prognostic value of CD44v6 expression among GEP-NENs.

MATERIALS AND METHODS

Immunohistochemical staining (IHC) of CD44v6 was studied in 26 formalin-fixed-paraffin-embedded (FFPE) specimens from GEP-NENs patients in the Srinagarind Hospital, Khon Kaen University, Thailand, between 2013 and 2018. Demographic data were collected. IHC staining result was interpreted based on H-score and correlated with neuroendocrine IHC markers, proliferation index, lymph nodes status, metastasis, and patients' survival.

RESULTS

All cases showed variable staining for CD44v6 without statistically significant correlation with age, gender, histological grading, lymph node metastasis, distant metastasis, Ki-67 proliferative index, or neuroendocrine marker expression. Survival analysis showed association of higher CD44v6 expression with better prognosis (p = 0.033). Hazard ratio of CD44v6 low expression patients with age ≥ 49 was 12.736 (p = 0.028, 1.318-123.073), presence of lymph node metastasis was 8.267 (p = 0.036, 1.142-59.841), presence of distant metastasis 12.736 (p = 0.028, 1.318-123.073).

CONCLUSION

Higher expression of CD44v6 IHC is significantly associated with better overall survival, histological grading, and Ki-67 index of GEP-NENs patients. CD44v6 IHC can be used as an additional prognostic immunohistochemical marker related to the metastatic status.

摘要

背景

胃肠胰神经内分泌肿瘤（GEP-NEN）患者的临床病程由复杂和多方面的因素决定。Ki-67 已被用于预测具有统计学显著高概率的 NEN 行为。除了 Ki-67 以外，还有其他免疫组织化学预后标志物已被报道，但由于验证不足，尚未常规使用。CD44 及其同工型变体与胰腺神经内分泌肿瘤（Pan-NEN）的淋巴结状态、远处转移和死亡率呈显著负相关。本研究旨在确定 CD44v6 在 GEP-NEN 中的表达的预后价值。

材料和方法

对 2013 年至 2018 年在泰国孔敬大学诗琳通医院的 26 例 GEP-NEN 患者的福尔马林固定石蜡包埋（FFPE）标本进行了 CD44v6 的免疫组织化学染色（IHC）。收集了人口统计学数据。根据 H 评分解释 IHC 染色结果，并与神经内分泌 IHC 标志物、增殖指数、淋巴结状态、转移和患者生存相关联。

结果

所有病例均显示 CD44v6 的可变染色，但与年龄、性别、组织学分级、淋巴结转移、远处转移、Ki-67 增殖指数或神经内分泌标志物表达无统计学显著相关性。生存分析显示，较高的 CD44v6 表达与较好的预后相关（p=0.033）。年龄≥49 岁的 CD44v6 低表达患者的危险比为 12.736（p=0.028，1.318-123.073），存在淋巴结转移的危险比为 8.267（p=0.036，1.142-59.841），存在远处转移的危险比为 12.736（p=0.028，1.318-123.073）。