PO.ET06.06 · 实验与分子治疗
OTP、CD44、Ki67生物标志物组合可预测术前肺NET活检标本的预后
The OTP, CD44, Ki67 biomarker panel predicts prognosis in preoperative lung NET biopsy specimens
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
引言：此前，OTP、CD44和Ki-67已被确定为切除的肺神经内分泌肿瘤（肺NET，也称为肺类癌（LCs））中的预后生物标志物。
目的：我们旨在检验生物标志物OTP、CD44和Ki-67在术前LC活检中的预后价值。
方法：从荷兰病理档案（PALGA）中选取接受根治性切除的LC患者（按TNM 8重新分期为I-III期，2003-2022年）。识别匹配的切除（Rx）和活检（Bx）标本，并对OTP、CD44和Ki-67进行免疫组化（IHC）。由三位病理学家根据WHO 2021分类进行病理复核。评估OTP和CD44免疫染色（H评分），Ki-67增殖指数（PI）通过目测估计并采用热点评分。诊断为典型类癌（TC）或非特指类癌（NOS）的Bx病例归为低风险（即非非典型类癌或非AC）。生物标志物组合被分类为低风险（OTP≥50、CD44≥30、Ki-67<5%）或高风险（其他所有情况）。
结果：共有98例患者符合条件，其中19例患者在中位随访83.3个月后复发。生物标志物组合正确识别出89%（n=17/19）复发病例为高风险，优于WHO分类，后者仅将11%（n=2/19）的复发病例判定为AC。生物标志物组合的阴性预测值（NPV）为0.96，而WHO为0.82。生物标志物风险分层还显示出更高的评分者间一致性（生物标志物组合：κ=0.673；WHO：κ=0.276，两者均p<0.001）以及更佳的标本间一致性（生物标志物组合：κ=0.584，p<0.001；WHO：κ=0.169，p=0.037）。
结论：OTP、CD44和Ki-67免疫组化生物标志物组合大幅改善了对低风险LC患者的识别，且可应用于活检标本，其预后价值优于WHO分类。这可能影响手术治疗策略的选择。
查看英文原文 English abstract
Introduction: Previously OTP, CD44 and Ki-67 have been identified as prognostic biomarkers in resected lung neuroendocrine tumors (lung NETs, also known as lung carcinoids (LCs)).
Aims: We aimed to examine the prognostic value of biomarkers OTP, CD44 and Ki-67 in preoperative LC biopsies.
Methods: Patients with LC (reclassified TNM 8 stage I-III, 2003-2022) who underwent a curative resection were selected from Dutch pathology archives (PALGA). Matching resection (Rx) and biopsy (Bx) specimens were identified and immunohistochemistry (IHC) for OTP, CD44 and Ki-67 was performed. Pathology revision was carried out by three pathologists according to the WHO 2021 classification. OTP and CD44 immunostaining were assessed (H-score), and Ki-67 proliferation index (PI) by eyeball estimation with hot-spot scoring. Bx cases diagnosed as typical carcinoid (TC) or carcinoid not otherwise specified (NOS) were grouped as low risk (i.e. non-atypical carcinoid or non-AC). The biomarker panel was classified as low-risk (OTP≥50, CD44≥30, Ki-67<5%) or high-risk (all others).
Results: In total 98 patients were eligible, including 19 patients with a relapse after a median follow-up of 83.3 months. The biomarker panel correctly identified high-risk in 89% (n=17/19) of relapses, outperforming WHO classification, which assigned only 11% (n=2/19) of relapses as AC. Negative predictive value (NPV) of the biomarker panel was 0.96 compared to 0.82 for WHO. Biomarker risk stratification also showed higher inter-rater agreement (biomarker panel: κ=0.673; WHO: κ=0.276, both p<0.001) and improved inter-specimen concordance (biomarker panel: κ=0.584, p<0.001; WHO: κ=0.169, p=0.037).
Conclusion: An OTP, CD44 and Ki-67 IHC biomarker panel substantially improves identification of patients with low-risk LCs and is applicable on biopsy specimens, outperforming the prognostic value of WHO classification. This may influence the choice of surgical treatment strategy.
利益披露 Disclosure
T. J. van Weert, None..
L. Moonen, None..
L. M. Hillen, None.
J. von der Thüsen,
BMS Other, Consulting or Advisory role.
MSD Other, Consulting or Advisory role.
Lilly Other, Consulting or Advisory role.
AbbVie Other, Consulting or Advisory role.
AstraZeneca Other, Consulting or Advisory role.
J&J Travel, Other, Speakers'Bureau.
M. A. den Bakker, None..
L. M. Lap, None..
P. Group, None..
R. A. Damhuis, None..
W. A. Buikhuisen, None.
A. C. Dingemans,
Roche/Genetech Other, Consulting or Advisory role.
AstraZeneca Other, Consulting or Advisory role.
J&J Other, Consulting or Advisory role
Speakers'Bureau.
Pfizer Other, Consulting or Advisory role.
BMS Other, Consulting or Advisory role.
BeiGene Consulting or Advisory role.
BeOne Other, Consulting or Advisory role
Speakers'Bureau.
Boehringer Ingelheim Other, Consulting or Advisory role.
MSD Consulting or Advisory role.
J. L. Derks,
Ipsen Other, Consulting or Advisory role.
E. M. Speel,
Pfizer ).
J&J Other, Advisory Board.
Illumina Other, Advisory Board.