Abstract

Recent investigations strongly suggest that Raman spectroscopy (RS) can be used as a clinical tool in cancer diagnosis to improve diagnostic accuracy. In this study, we evaluated the efficiency of Raman imaging microscopy to discriminate between healthy and neoplastic thyroid tissue, by analyzing main variants of Papillary Thyroid Carcinoma (PTC), the most common type of thyroid cancer. We performed Raman imaging of large tissue areas (from 100 × 100 μm2 up to 1 × 1 mm2), collecting 38 maps containing about 9000 Raman spectra. Multivariate statistical methods, including Linear Discriminant Analysis (LDA), were applied to translate Raman spectra differences between healthy and PTC tissues into diagnostically useful information for a reliable tissue classification. Our study is the first demonstration of specific biochemical features of the PTC profile, characterized by significant presence of carotenoids with respect to the healthy tissue. Moreover, this is the first evidence of Raman spectra differentiation between classical and follicular variant of PTC, discriminated by LDA with high efficiency. The combined histological and Raman microscopy analyses allow clear-cut integration of morphological and biochemical observations, with dramatic improvement of efficiency and reliability in the differential diagnosis of neoplastic thyroid nodules, paving the way to integrative findings for tumorigenesis and novel therapeutic strategies.

Highlights

  • Discriminant Analysis (LDA), were applied to translate Raman spectra differences between healthy and papillary thyroid carcinomas (PTC) tissues into diagnostically useful information for a reliable tissue classification

  • Raman spectroscopic study, performed using a Raman imaging microscope (RM), was carried out for nine patients, which underwent total thyroidectomy and received a diagnosis of PTC based on Fine needle aspiration biopsy (FNA) at the Endocrinology Unit of University Campus Bio-medico of Rome (UCBM)

  • Our results have demonstrated the feasibility and reproducibility of Raman spectroscopy (RS) to discriminate between normal thyroid tissue and PTC, and between classical and follicular variants of PTC, on the basis of their biochemical fingerprints

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Summary

Introduction

Discriminant Analysis (LDA), were applied to translate Raman spectra differences between healthy and PTC tissues into diagnostically useful information for a reliable tissue classification. Technological advances over the last decade have created innovative RS based tools, providing morphological investigation of large tissue areas coupled with high resolution, point-by-point spectral analysis of biochemical composition Such a technological development has prompted a burst of rapidly growing, clinically-driven RS investigations, leading to several in vivo applications of RS in biomedicine[4,5,6,7,8]. Molecular analysis of FNA biopsy from thyroid nodules has been performed in order to reduce the number of cytologically indeterminate cases, with the development of several diagnostic panels[12] Through these advances, molecular diagnostics has improved the care of patients with thyroid nodules and cancer[13]; the cost of such procedures, should be reduced in order to increase their cost-effectiveness in standard medical. Genetic molecular analysis, even if extensive, does not provide any information about the biochemical profile of these tumors

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