Mutational and clinico-pathological analysis of papillary thyroid carcinoma in Serbia

Abstract

Thyroid cancer is the most prevalent type of endocrine malignancy. During the past decades its incidence has been increasing in many countries [1]. Papillary thyroid carcinoma (PTC) accounts for more than 80% of all thyroid cancers and for 95% of this increase [2]. About 70% of the newly diagnosed PTCs are small 852-8523, JapanAbstract. Molecular pathogenesis of papillary thyroid carcinoma (PTC) is largely associated with mutational changes in the BRAF, RAS family and RET genes. Our aim was to assess clinico-pathological and prognostic correlations of these PTCspecific gene alterations, with a particular emphasis on the BRAF mutation, in a group of 266 Serbian PTC patients, for the first time. The reference center-based retrospective cohort included 201 (75.6%) females and 65 (24.4%) males aged 48.0±16.1 years (8 -83 years old, range) diagnosed and treated for PTC during 1993-2008. Follow-up period was 53.1±41.6 months (7-187 months, range). BRAF and RAS mutations were determined by direct sequencing of genomic DNA. RET/ PTC rearrangements were analyzed by RT-PCR/Southern blotting. Genetic alterations were detected in 150/266 tumors (56.4%). One tumor displayed two genetic alterations. The BRAF V600E was found in 84/266 (31.6%) cases, RAS mutations in 11/266 (4.1%) and RET/PTC in 55/266 (20.7%; 42/266 (15.8%) RET/PTC1 and 13/266 (4.9%) RET/PTC3). On multivariate analysis BRAF V600E was associated with the classical papillary morphology (P = 0.05), the higher pT category (P = 0.05) and advanced clinical stage (P = 0.03). In a proportional hazard model, BRAF V600E did not appear to be an independent risk factor for the faster recurrence (P = 0.784). We conclude that under the extensive thyroid surgery and limited application of radioiodine ablation BRAF V600E may not be an indicator of poorer disease-free survival during the short to middle follow-up period. However, it has a potential to contribute to patients stratification into high-and low-risk groups.

Lymphatic drainage, regional metastases and surgical management of papillary thyroid carcinoma arising in pyramidal lobe – a single institution experience

“…Clinically, they appeared as a palpable, rigid mass, visible in the midline of the neck and FNAB showed lesion suspicious for PTC. We performed TT to exclude PTC multifocality [17,19], to prevent PTC recurrence, especially nondifferentiated, anaplastic carcinoma in thyroid remnant [7,8,17,18] and to increase the sensitivity of serum thyroglobulin in the follow-up period [10].…”

Surgical management of primary thyroid carcinoma arising in thyroglossal duct cyst: An experience of a single institution in Serbia

“…All patients were diagnosed as TDC carcinoma also on postoperative pathological examination. Molecular analysis of BRAF gene was also performed for these tumors by the standard technical procedure [9].…”

Long-Term Prognosis of Differentiated Thyroid Cancer with Lung Metastasis in Korea and Its Prognostic Factors

“…In Korea, the incidence of thyroid cancer is also rapidly increasing; the incidence rates per 100,000 persons adjusting for age increased from 2.1 (in 1999) to 15.4 (in 2009) in males and 10.4 (in 1999) to 79.6 (in 2009) in females (23)-rates that are higher than in any other country studied (24). Furthermore, Korean DTCs have several distinguishing characteristics: (i) family history of DTC is twofold higher than in other studies (25), (ii) PTC is more frequent (more than 90%) (26), and (iii) DTC patients had higher rates of BRAF V600E mutations (58-81%) (27)(28)(29) in Korea than in any other country (30). Environmentally, Korea is one of the iodinesufficient areas in the world (31).…”