| Papillary thyroid carcinoma (PTC), which accounts for up to 75%-80%of all thyroid cancer, is one of rapidly growing endocrine neoplasm. Surgery, postoperative radioactive iodine 131 treatment and thyroid hormone suppressive therapy are the main treatment modalities for PTC. Recent studies have shown that BRAF gene mutation is asscociated with PTC genesis, development, and decrease of both Na+/I- symporter (NIS) and iodide-metabolizing genes expression. The aim of this study is to evaluate the BRAF gene mutation, NIS protein expression in PTC in Shandong coastal areas (such as Qingdao, etc.). Meanwhile, the initial surgical procedure on the prognosis of PTC were also investigated.Section 1 BRAF mutation and NIS expression in PTCObjective:To investigate the BRAF gene mutation, NIS expression and their relationship in Shandong coastal areas PTC patients cancer tissues and cancerous surrounding tissues.Methods:Paraffin-embedded tissues blocks with 138 PTCs were obtained from the Pathology Department of the affiliated hospital of Qingdao University Medical College between January 1,2008 and January 1,2011 in this study. Including 66 PTCs with the surrounding normal tissues (abbreviated as Gnormal) and another 72 PTCs with the surrounding nodular goiter tissues (abbreviated as Gng). DNA was extracted from paraffin-embedded tumor specimens, and the presence of the BRAFV600E mutation was evaluated using PCR amplification and direct sequencing in 15 cases of each group.Then all the 138 PTCs’cancer tissues and cancerous surrouding tissues sections were subjected to immunohistochemistry (IH) using a Rabbit Anti-NIS Polyclonal Antibody.The expression of NIS protein were observed by immunohistochemical scores(IHS).Results:There was no BRAFV60 E gene mutation in 30 PTC cases. Expression levels of NIS protein were lower in PTC surrounding nodular goiter tissues than that of the cancerous tissues (276 points/348 points, p=0.006). NIS protein levels were also lower in the PTC surrounding nodular goiter tissues than that of the adjacent normal thyroid tissues (276 points/351 points,p=0.002). NIS protein levels in PTC with nodular goitor tissues were lower than that of PTC with normal tissues, while no significant difference was observed between two group (348 points/366 points,p=0.075)Conclusion:No BRAFV600E mutation in this PTC cases. BRAFV600E could not be proposed to relate with genesis of PTC in Shandong coastal area. Expression levels of NIS protein were lower in the adjacent nodular goiter tissues than that of the surrounding normal tissues. NIS express differently in papillary thyroid carcinoma with different surrounding tissues which could induce the subsequent RAI uptake activity difference. This may indicated that PTC with surrounding nodular goiter tissues may has an adverse efficacy of RAI therapy.Section 2 Prognosis of papillary thyroid carcinoma influenced by initial surgical procedureObjective:To analyze the choice of initial surgical procedure on the prognosis of papillary thyroid carcinoma (PTC).Method:Retrospective analysis of 445 (Female 329, Male 116) PTC patients (Department of Nuclear Medicine, Peking Union Medical College Hospital) after surgery and scheduled for 131I treatment with either tumor size larger than lcm or tumor size equal or less lcm but combined with extra-capsule invasion or lymph node metastasis or distant metastasis. According to whether the first surgical procedure performed as total or subtotal thyrodectomy or not,445 PTC patients were divided into G1 and G2 groups.The relationship between prognosis and factors such as age, gender, tumor size, lymph node metastasis and capsule invasion, operation times and initial surgical procedure was evaluated. Recurrence rate, emotional scales as well as economic cost of the second surgery for PTC recurrence and prognosis influenced by improper initial surgical procedure were emphasized.Results:Poor prognostic variables including extra-capsule invasion (p=0.001), operation times (p=0.000), the initial operation pattern (p=0.000) by univariate analysis and extra-capsule invasion(p=0.001), operation times (p=0.000) by multivariate analysis. After 3 months,1 year,5 years,10 years follow-up, G2 group of all time after recurrence was significantly higher than that of the G1 group (p all<0.05).The mean standard scores of Self-Rating Anxiety Scale in G1, G2 were (37.5±8.0) points, (40.6±11.26) points respectively, which were higher than that of normal adults (29.78±0.07) in China (p=0.000, tG1=6.031, tG2= 7.068). There was significant difference between G1 and G2 groups (P=0.000, t=5.034). Mean standard scores of Self-Rating Depression Scale in G1 and G2 groups were (43.31±10.38) points, (46.85±11.86) points respectively, which were higher than that scores of normal adults (33.46±8.55) in China (p all<0.05, tG1=5.974,tG2= 6.466). G1, G2 between the two groups was statistically different (p=0.017, t= 2.574). Heavier economic burden induced by reoperation for patients was observed with at least additional 7,228 yuan, which is 1.8 times the cost of treatment than whom with one operation (p=0.000, t=6.537).Conclusion:The extent of initial surgery is a vital factor for the prognosis of papillary thyroid cancer. Initial improper surgical procedure caused poor prognosis and high recurrence which will increase the patients’ mental and economic burden, affect their quality of life. |
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