Diagnostic Usefulness of Tumor Markers in the Thyroid Cytological Samples Extracted by Fine-Needle Aspiration Biopsy

Abstract

Thyroid nodules are quite common and present approximately in 10% of the population. Fine-needle aspiration biopsy has become the mainstay of thyroid nodule evaluation and the overall accuracy is excellent; however, some aspirates demonstrating indeterminate cytology results do not permit definitive diagnosis of malignancy, and in addition, there are no clear guidelines for the management of these lesions because the incidence of malignancy in indeterminate aspirates varies in the different studies published. In order to find molecular markers in an attempt to predict malignancy based on cytology, at least 70 molecular or cellular and genetic markers have been studied in thyroid nodules. This review focuses on some potential markers such as thyroid peroxidase, thyroglobulin, telomerase, galectin-3, RET/PTC and protein p53; some of them, such as thyroid peroxidases, thyroglobulin and galectin-3, can be studied in a routine pathology laboratory and are promising, but do not yet fulfil criteria required for their use in clinical practice. The American guidelines and the European consensus for the management of thyroid nodules and differentiated thyroid cancer do not recommend their systematic use because the evidence that they have provided is insufficient. On the other hand, information obtained through cytological smears permits the study of complex metabolic or genetic pathways, providing researchers with a high throughput tool to elucidate changes in the global expression patterns seen in tumour cells. This ability to take tumour biology into account would allow the selection of different drugs, considering the predominant altered pathways observed in these samples. Finally, all these data may provide the molecular groundwork for permitting future preoperative discrimination of follicular adenomas from hyperplastic nodules, and may ultimately guide therapeutic strategies.

Cytology specimens offer an effective alternative to formalin‐fixed tissue as demonstrated by novel automated detection for ALK break‐apart FISH testing and immunohistochemistry in lung adenocarcinoma

“…To the best of our knowledge, there are few published studies to date that use cytologic material for molecular analysis, and these are usually limited to FFPE blocks and direct smears . Fine‐needle aspiration (FNA) specimens pose additional challenges over tissue biopsy or surgical resection.…”

Assessment of molecular testing in fine-needle aspiration biopsy samples: An experience in a Chinese population

“…Various genetic alterations have been described in thyroid cancer during the last two decades, and molecular markers of thyroid cancer have been used in clinical practice to refine fine needle aspiration diagnosis of thyroid nodules (Gomez Saez, 2010;Nikiforova and Nikiforov, 2009). Genetic mutations including the BRAF V600E mutation, RAS point mutation and RET/PTC rearrangement have been widely studied in papillary and follicular thyroid carcinoma, which are the two most common thyroid cancers (~90 to 95%) originating from the thyroid follicular epithelium (Nikiforov and Nikiforova, 2011).…”

Is there a real diagnostic impact of elastosonography and contrast-enhanced ultrasonography in the management of thyroid nodules?

“…Molecular biology techniques, such as searching for genetic alterations (Nikiforova et al, 2003;Gomez Saez, 2010) or protein expression (Bartolazzi et al, 2008;Gomez Saez, 2010), have not yet led to a significant improvement in distinguishing cases of thyroid malignancy from those of inadequate or indeterminate cytology. On the other hand, the role of US in this effort is complex, being both operator-and machine-dependent and linked to an adequate standardized terminology.…”