Validation of molecular biomarkers for preoperative diagnostics of human papillary thyroid carcinoma in fine needle aspirates

Sadowski, Samira M.; Petrenko, Volodymyr; Meyer, Patrick; Pusztaszeri, Marc; Brulhart‐Meynet, Marie‐Claude; Masson, M; Triponez, Frédéric; Philippe, Jacques; Dibner, Charna

doi:10.21037/gs.2018.11.04

Cited by 11 publications

(22 citation statements)

References 49 publications

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“…In the past 10 years, we have witnessed significant progress in the field of the molecular pathogenesis of thyroid carcinoma based on studies using NGS. In 2014, The Cancer Genome Atlas testing for discriminating malignancy from benignity were 63%-94% and 52%-99%, respectively, with FNB [19][20][21]. Regardless of how sensitive or specific it is, applying gene testing to FNB is limited in clinical practice because specialized sample collection is required at the time of the initial procedure.…”

Section: Results Of Ngsmentioning

confidence: 99%

Value of biomarkers in distinguishing indeterminate core needle biopsy samples of thyroid nodules

Xiong

Yan

et al. 2020

Preprint

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Background: Core needle biopsy (CNB) is now more frequently used for the preoperative diagnosis of thyroid nodules. Based on morphology alone, 5%-20% of CNB samples cannot be determined as malignant or benign. Compared to fine-needle biopsy (FNB), samples collected by CNB are more accessible for various tests. Therefore, studying the application of biomarkers in distinguishing indeterminate CNB samples of thyroid nodules is a practical need. Methods: Patients with thyroid nodules with both CNB and matched resected specimens were reviewed. Cases classified as indeterminate lesions, follicular neoplasms and suspicious for malignancy were retrieved. All CNB samples were stained by immunohistochemistry (IHC) using antibodies against CK19, Galectin-3, HBME-1, and CD56 and detected by next-generation sequencing (NGS) using a target panel. With the help of these biomarkers, all CNB samples were reclassified. Taking the classification of resected specimens as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of each biomarker for discriminating malignancy from benignity were calculated. Results: The sensitivity, specificity, PPV, NPV and accuracy were 93.55%, 60.00%, 93.55%, 60.00% and 88.89% for CK19; 93.55%, 40.00%, 90.63%, 50.00% and 86.11% for Galectin-3; 77.42%, 100.00%, 100.00%, 41.67% and 80.56% for HBME-1; 66.13%, 100.00%, 100.00%, 32.26% and 70.83% for CD56; and 91.94%, 100.00%, 100.00%, 66.67% and 93.06% for pathogenic mutation. Conclusions: The application of biomarkers is very effective in distinguishing indeterminate CNB samples of thyroid nodules. Gene testing by NGS using a target panel has very high accuracy. The limitation of tumor quantity is the main reason for the weakened power of NGS. IHC plays an important role in cases with negative NGS results. The combination of NGS and IHC is a reliable “rule in” test for malignancy.

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Section: Results Of Ngsmentioning

confidence: 99%

Value of biomarkers in distinguishing indeterminate core needle biopsy samples of thyroid nodules

Xiong

Yan

et al. 2020

Preprint

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“…Based on their understanding of thyroid carcinoma's mutational profile, researchers have tried to use diverse molecular approaches to improve diagnosing uncertain biopsy samples and have presented various published results. The sensitivity and specificity of gene testing for discriminating malignancy from benignity were 63-94% and 52-99%, respectively, with FNB [19][20][21]. Regardless of how sensitive or specific it is, applying gene testing to FNB is inconvenient in clinical practice because specialized sample collection is required at the initial procedure.…”

Section: Discussionmentioning

confidence: 99%

Application of biomarkers in the diagnosis of uncertain samples of core needle biopsy of thyroid nodules

Xiong

Liang

et al. 2021

Virchows Arch

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Core needle biopsy (CNB) is now more frequently used for the preoperative diagnosis of thyroid nodules. Based on morphology alone, 5–20% of CNB samples cannot be determined as malignant or benign. Compared to fine-needle biopsy (FNB), samples collected by CNB are more accessible for various tests. Therefore, studying biomarkers’ application in distinguishing uncertain CNB samples of thyroid nodules is a practical need. Patients of thyroid nodules with both CNB and matched resected specimens were reviewed. Cases classified as indeterminate lesions, follicular neoplasms, and suspicious for malignancy were retrieved. All CNB samples were stained by immunohistochemistry (IHC) using antibodies against CK19, galectin-3, HBME-1, and CD56 and detected by next-generation sequencing (NGS) using an OncoAim® thyroid cancer multigene assay kit (Singlera Genomics) that detected 26 genes. Taking the resected specimens’ classification as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy of a single biomarker, and various combinations for discriminating malignancy from benignity were calculated. The sensitivity, specificity, PPV, NPV, and accuracy for preoperative malignancy evaluation were as follows. In the cohort of non-follicular-neoplasm-lesions (non-FN-lesion), they were 95.16%, 53.85%, 90.77%, 70.00%, and 88.00% for CK19; 95.16%, 38.46%, 88.06%, 62.50%, and 85.33% for galectin-3; 77.42%, 76.92%, 94.12%, 41.67%, and 58.00% for HBME-1; 66.13%, 100.00%, 100.00%, 38.24%, and 72.00% for CD56; 90.32%, 92.31%, 98.25%, 66.67%, and 90.67% for NGS; and 88.71%, 92.30%, 98.21%, 63.16%, and 89.33% for integrated IHC. In the cohort of follicular neoplasms (FN), they were 30.43%, 77.77%, 77.77%, 30.43%, and 43.75% for CK19; 73.91%, 66.67%, 85.00%, 50.00%, and 71.88% for galectin-3; 26.09%, 88.89%, 85.71%, 32.00%, and 43.75% for HBME-1; 26.09%, 100.00%, 100.00%, 34.62%, and 46.88% for CD56; 52.17%, 88.89%, 92.31%, 42.11%, and 62.50% for NGS; 82.61%, 66.67%, 86.36%, 60.00%, and 78.13% for integrated IHC; and 100%, 66.67%, 88.46%, 100%, and 90.63% for integrated IHC-NGS. The application of biomarkers in distinguishing uncertain CNB samples of thyroid nodules is available and capable. CD56 negative or NGS positive suggests malignancy strongly for both FN and non-FN-lesion, which may be used as a “rule in” tool. The negative predictive value of the integrated IHC and the integrated IHC-NGS implies a high possibility to be benign for non-FN-lesion and FN separately, which can work as a “rule out” tool. Considering the balance of specificity and sensitivity, NGS is the best for non-FN-lesion and the integrated IHC-NGS is the best for FN.

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“…For example, studies in human primary thyrocytes indicated that progression of papillary thyroid carcinoma is paralleled with altered synchronization properties of these cells [394]. Although causality often remains unexplored in these studies, changed expression levels of individual core clock genes have clearly been linked to the progression of oncogenic transformation, making them plausible candidates for diagnostic biomarkers [228,312,394,400,[408][409][410][411].…”

Section: Circadian Clock Perturbation and Human Diseasesmentioning

confidence: 99%

“…Today, increasing numbers of immediate clinical applications emerge from recent studies of human clocks in their physiological state, as well as under pathological conditions. Utilizing individual clock properties as molecular biomarkers holds promise for personalized medicine approaches, as well as for diagnostic purposes [372,408,432]. Chronopharmacology that takes into account circadian pharmacokinetics and pharmacodynamics already plays an important role for a number of medications widely used for treating oncological, metabolic, and respiratory diseases [433,434].…”

Section: Perspectivesmentioning

confidence: 99%

Coupled network of the circadian clocks: a driving force of rhythmic physiology

2020

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The circadian system is composed of coupled endogenous oscillators that allow living beings, including humans, to anticipate and adapt to daily changes in their environment. In mammals, circadian clocks form a hierarchically organized network with a ‘master clock’ located in the suprachiasmatic nucleus of the hypothalamus, which ensures entrainment of subsidiary oscillators to environmental cycles. Robust rhythmicity of body clocks is indispensable for temporally coordinating organ functions, and the disruption or misalignment of circadian rhythms caused for instance by modern lifestyle is strongly associated with various widespread diseases. This review aims to provide a comprehensive overview of our current knowledge about the molecular architecture and system‐level organization of mammalian circadian oscillators. Furthermore, we discuss the regulatory roles of peripheral clocks for cell and organ physiology and their implication in the temporal coordination of metabolism in human health and disease. Finally, we summarize methods for assessing circadian rhythmicity in humans.

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Validation of molecular biomarkers for preoperative diagnostics of human papillary thyroid carcinoma in fine needle aspirates

Cited by 11 publications

References 49 publications

Value of biomarkers in distinguishing indeterminate core needle biopsy samples of thyroid nodules

Value of biomarkers in distinguishing indeterminate core needle biopsy samples of thyroid nodules

Application of biomarkers in the diagnosis of uncertain samples of core needle biopsy of thyroid nodules

Coupled network of the circadian clocks: a driving force of rhythmic physiology

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