Abstract

BackgroundDistinguishing lung adenocarcinoma (ADC) from squamous cell carcinoma (SCC) has a tremendous therapeutic implication. Sometimes, the commonly used immunohistochemistry (IHC) markers fail to discriminate between them, urging for the identification of new diagnostic biomarkers.MethodsWe performed IHC on tissue microarrays from two cohorts of lung cancer patients to analyse the expression of beta-arrestin-1, beta-arrestin-2 and clinically used diagnostic markers in ADC and SCC samples. Logistic regression models were applied for tumour subtype prediction. Parallel reaction monitoring (PRM)-based mass spectrometry was used to quantify beta-arrestin-1 in plasma from cancer patients and healthy donors.ResultsBeta-arrestin-1 expression was significantly higher in ADC versus SCC samples. Beta-arrestin-1 displayed high sensitivity, specificity and negative predictive value. Its usefulness in an IHC panel was also shown. Plasma beta-arrestin-1 levels were considerably higher in lung cancer patients than in healthy donors and were higher in patients who later experienced a progressive disease than in patients showing complete/partial response following EGFR inhibitor therapy.ConclusionsOur data identify beta-arrestin-1 as a diagnostic marker to differentiate ADC from SCC and indicate its potential as a plasma biomarker for non-invasive diagnosis of lung cancer. Its utility to predict response to EGFR inhibitors is yet to be confirmed.

Highlights

  • Lung cancer is the deadliest cancer worldwide

  • IHC results are concordant with the diagnosis: ADC samples express Transcription Factor 1 (TTF1), Napsin A (NAPSA) and keratin 7 (KRT7), whereas squamous cell carcinoma (SCC) samples express keratin 5-6 (KRT5-6) and p63

  • We provided evidence that beta-arrestin-1 can effectively differentiate between lung ADC and lung SCC, and demonstrated its usefulness as a diagnostic marker in an IHC panel

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Summary

Introduction

Targeted drugs approved for the treatment of specific NSCLC subtypes were either ineffective or harmful if used in other NSCLC groups.[3,4] In this regard, distinguishing between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) has a tremendous therapeutic implication.[5,6,7,8,9]. METHODS: We performed IHC on tissue microarrays from two cohorts of lung cancer patients to analyse the expression of betaarrestin-1, beta-arrestin-2 and clinically used diagnostic markers in ADC and SCC samples. CONCLUSIONS: Our data identify beta-arrestin-1 as a diagnostic marker to differentiate ADC from SCC and indicate its potential as a plasma biomarker for non-invasive diagnosis of lung cancer. Its utility to predict response to EGFR inhibitors is yet to be confirmed

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