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-675%) 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 p0.001) and improved inter-specimen concordance (biomarker panel: κ=0.584, p0.001; 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. Citation Format: Tijmen JJ van Weert, Laura Moonen, Lisa M. Hillen, Jan von der Thüsen, Michael A. den Bakker, Lisa MV Lap, PALGA Group, Ronald A. Damhuis, Wieneke A. Buikhuisen, Anne-Marie C. Dingemans, Jules L. Derks, Ernst Jan M. Speel. The OTP, CD44, Ki67 biomarker panel predicts prognosis in preoperative lung NET biopsy specimens abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7215.
Weert et al. (Fri,) studied this question.
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