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Assessing fractional hair cell survival in archival human temporal bones.

ABSTRACT: OBJECTIVES/HYPOTHESIS:Histopathological analysis of hair cell survival in human temporal bone sections has historically been binarized such that each hair cell row is rated as either present or absent, thereby greatly underestimating the amount of hair cell loss. Here, we describe and validate a technique to reliably assess fractional hair cell survival in archival sections stained with hematoxylin and eosin (H&E) using high-resolution light microscopy and optical sectioning. STUDY DESIGN:Technique validation. METHODS:Hair cell counts in archival temporal bone slide sets were performed by several observers using either differential interference contrast (DIC) or confocal microscopy of the endogenous eosin fluorescence in hair cells. As a further cross-check, additional decelloidinized sections were immunostained with hair cell markers myosin VI and VIIa. RESULTS:Cuticular plates and stereocilia bundles are routinely resolvable in DIC imaging of archival H&E-stained human material using standard research-grade microscopes, allowing highly accurate counts of fractional hair cell survival that are reproducible across observer and can be verified by confocal microscopy. CONCLUSIONS:Reanalysis of cases from the classic temporal bone literature on presbycusis suggests that, contrary to prior reports, differences in audiometric patterns may be well explained by the patterns of hair cell loss. LEVEL OF EVIDENCE:NA Laryngoscope, 130:487-495, 2020.

SUBMITTER: Wu PZ

PROVIDER: S-EPMC6783317 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Assessing fractional hair cell survival in archival human temporal bones.

Wu Pei-Zhe PZ Wen Wei-Ping WP O'Malley Jennifer T JT Liberman M Charles MC

The Laryngoscope 20190408 2

<h4>Objectives/hypothesis</h4>Histopathological analysis of hair cell survival in human temporal bone sections has historically been binarized such that each hair cell row is rated as either present or absent, thereby greatly underestimating the amount of hair cell loss. Here, we describe and validate a technique to reliably assess fractional hair cell survival in archival sections stained with hematoxylin and eosin (H&E) using high-resolution light microscopy and optical sectioning.<h4>Study de ...[more]

PMID: 30963586

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Project description:BACKGROUND:In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data. PATIENTS AND METHODS:PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10?mg/kg Q3W or docetaxel 75?mg/m2 Q3W for 24?months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9?weeks, survival every 2?months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ?50% and ?1%; pembrolizumab doses were pooled in this analysis. RESULTS:At date cut-off of 24 March 2017, median follow-up was 31?months (range 23-41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 [95% confidence interval (CI): 0.57, 0.77]. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ?50%. For TPS ?50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ?1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ?50%, PFS HRs were similar across archival [0.63 (95% CI: 0.45, 0.89)] and newly collected samples [0.53 (95% CI: 0.38, 0.72)]. In patients with TPS ?1%, PFS HRs were similar across archival [0.82 (95% CI: 0.66, 1.02)] and newly collected samples [0.83 (95% CI: 0.68, 1.02)]. CONCLUSION:Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01905657.

Dataset Information

Assessing fractional hair cell survival in archival human temporal bones.

Publications

Assessing fractional hair cell survival in archival human temporal bones.

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