Novel molecular markers in well-differentiated thyroid cancers

Abstract

Conventional cytopathology is an excellent tool for distinguishing benign from malignant thyroid nodules with high sensitivity and specificity. However, significant numbers of cases are indeterminate, resulting in many ultimately unnecessary diagnostic thyroidectomies. Numerous molecular markers have been studied in an attempt to improve the diagnostic accuracy of thyroid fine-needle aspiration cytology. Several markers, such as galectin-3 and thyroid peroxidase, have been extensively assessed and shown not only to differentiate malignant tumors from benign thyroid lesions with high sensitivity and specificity, but also to identify tumors associated with poor outcome. More recently, four other genes (PTTG, PBF, BRAF and MUC1) have been identified that show real promise as potential molecular markers in thyroid cancer, offering discrimination between tumor subtypes and providing valuable prognostic information. However, larger, well-controlled studies are needed before their introduction into routine clinical practice. The search for molecular markers represents one of the most exciting areas in translational thyroid cancer research. We are optimistic that molecular markers will be used in the near future as adjuncts to conventional histological techniques to improve diagnostic accuracy of fine-needle aspiration cytology for thyroid lesions, particularly those that are cytologically indeterminate. Expert Rev. Endocrinol. Metab. 1(5), 685-693 (2006) Search for molecular markersThyroid cancer is the most common endocrine cancer, accounting for approximately 90% of all endocrine tumors, and its incidence is increasing worldwide [1][2][3]. Despite advances in treatment, recurrence still occurs in approximately 20% of cases, most commonly as local nodal metastases and less often as distant hematogenous metastases, leading to substantial morbidity and premature mortality [4].Thyroid nodules are very common with approximately 5-10% of the population having palpable thyroid nodules [5]. Differentiation between benign and malignant nodules represents an important clinical diagnostic challenge. Fine-needle aspiration cytology (FNAC) is widely established as a reliable and effective procedure in the clinical management of thyroid nodules [6]. Despite high sensitivity and specificity, significant numbers of cases (10-25%) are indeterminate, usually failing to differentiate between benign follicular lesions and follicular thyroid cancers [7,8]. These cases require surgery in the form of hemi-thyroidectomy to achieve diagnosis. Only 20-25% of these nodules are ultimately found to be malignant; therefore, 75-80% of patients undergo an unnecessary operation [1,9]. In addition, currently available standard histopathology and cytology techniques do not provide prognostic information regarding prediction of future recurrences. Risk assessment based upon clinical factors, such as age and gender, is relied upon to assist in differentiating high-risk patients.The population undergoing surveillance for recurrent thyroid cancer is many t...