Raman spectroscopy for the preoperative diagnosis of thyroid cancer and its subtypes: An in vitro proof‐of‐concept study

Abstract

Objective: In 2016, there were an estimated 56 870 new cases of thyroid cancer (TC) in the USA. Fine needle aspiration cytology (FNAC) is the most safe, accurate and cost-effective method for the initial investigation of thyroid nodules. FNAC is limited by the inability to diagnose malignancy in follicular-patterned lesions accurately and, as a result, 20%-30% of cases under investigation for TC are classified as cytologically indeterminate, illustrating a problem with current FNAC procedure.Raman spectroscopy has shown promising results for the detection of many cancers; however, to date there has been no report on the performance of Raman spectroscopy on thyroid cytological samples. The aim of this study was to examine whether Raman spectroscopy could be used to correctly classify cell lines representing benign thyroid cells and various subtypes of TC.Methods: A benign thyroid cell line and seven TC cell lines were prepared as Thin-Prep® cytology slides and analysed with Raman spectroscopy. Principal components analysis and linear discriminant analysis were implemented to develop effective diagnostic algorithms for classification of Raman spectra of different TC subtypes.Results: The spectral differences separating benign and TC cell lines were assigned to differences in the composition of nucleic acids, lipids, carbohydrates and protein in the benign and cancer cells. Good sensitivities (74%-85%), specificities (65%-93%) and diagnostic accuracies (71%-88%) were achieved for the identification of TC.Conclusion: These findings suggest that Raman spectroscopy has potential for preoperative TC diagnosis on FNAC samples. K E Y W O R D S cell lines, Raman spectroscopy, thyroid neoplasms, thyroid nodule 1 | INTRODUCTION In 2016, there were an estimated 56 870 new cases of thyroid cancer (TC) in the USA . 1 Women account for approximately 75% of these cases, exhibiting a substantially higher rate of incidence of the disease compared to men, but similar mortality. TC incidence has been steadily increasing in recent decades, as reported in the TC epidemiology studies. 2,3 Although improved diagnostic methods, notably ultrasound (US) examination, are the likely reason for the global increase in incidence (especially of smaller nodules), recent studies show that the incidence of aggressive forms associated with higher mortality is also increasing. 4 Of the wide array of malignancies that are characterised as TC, papillary thyroid carcinoma (PTC) is the most common, accounting for approximately 80% of cases. Other histological types include follicular thyroid carcinoma (FTC), Hürthle cell carcinoma, poorly differentiated carcinoma, medullary thyroid carcinoma (MTC), and O'Dea and Bongiovanni joint first authors. Lyng and Malkin joint senior authors.

Rationales for the Use of Cancer Stem Cells Markers in the Staging of Papillary Thyroid Carcinoma

“…In this respect, molecular biology methods represent the best choice to make the long road shorter. These methods employ the detection of the driver mutations in specific oncogenes to confirm the malignancy in biopsies of these tumors [29]. However, these tests do not give an idea about the prognosis of this disease.…”

Metabolic Profile Characterization of Different Thyroid Nodules Using FTIR Spectroscopy: A Review

“…Nevertheless, over the past few years, the metabolomics approach in terms of thyroid diagnosis has shown an enormous evolution, which is due, in part, to the application of several analytical techniques that allow the study of the complete set of small biomolecules that make up a biological sample. The main metabolomics techniques that have mostly been adopted in the thyroid, in an attempt to identify biomarkers, classify the thyroid cancer, facilitate an earlier diagnosis and prevent the development and invasion at the systemic level of the cancer itself, are Mass Spectrometry (MS) [53][54][55], Nuclear Magnetic Resonance (NMR) [53,56,57], Raman Spectroscopy [58][59][60] and Fourier Transform Infrared (FTIR) Spectroscopy [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79]. This increase in the number of studies is attributed to the greater availability of improved and accurate metabolomics techniques that exist and also due to the development of appropriate statistical tools that are able to handle the huge amount of data resulting from the samples under analysis [80].…”

A review of applications of Raman spectroscopy in immunology

“…Prior to its application in immunological research, Raman spectroscopy had been applied and proven in a range of disparate fields, including environmental and forensic sciences, archaeological studies, pharmaceutical detection and analysis, and semiconductor. Sophisticated applications of the technique for diagnosis of diseases including cancer [13,23,30,37,52] are now well established while novel applications to monitoring diabetes [39], detection of hyperbilirubinaemia [68], and observation of changes to the cervix during pregnancy [51] have emerged. In addition the sensitivity of Raman spectroscopy to biological effects occuring due to radiation exposure [43], radiotherapy [44] and chemotherapy [49] has also been demobstrated.…”