PO.ET06.06 · 实验与分子治疗

The OTP, CD44, Ki67 biomarker panel predicts prognosis in preoperative lung NET biopsy specimens

编号 7215 展板 7 时间 4/22 09:00–12:00 区域 Section 18 主讲 Ernst Jan Speel, PhD

分会场 Tumor Diagnostics, Prognostics, and Therapeutic Outcomes

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作者与单位

Tijmen JJ van Weert¹, Laura Moonen¹, Lisa M. Hillen¹, Jan von der Thüsen², Michael A. den Bakker³, Lisa MV Lap¹, PALGA Group⁴, Ronald A. Damhuis⁵, Wieneke A. Buikhuisen⁶, Anne-Marie C. Dingemans², Jules L. Derks², Ernst Jan M. Speel²

¹Maastricht University, Maastricht, Netherlands,²Erasmus MC Cancer Institute, Rotterdam, Netherlands,³Maasstad Hospital, Rotterdam, Netherlands,⁴PALGA Foundation, Utrecht, Netherlands,⁵Comprehensive Cancer Association, Utrecht, Netherlands,⁶Netherlands Cancer Institute, Amsterdam, Netherlands

摘要 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.

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