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Preoperative Detection Of Serum P53 Antibodies And BRAFV600E Mutation In Optimization Of Diagnosis And Surgical Treatment For Papillary Thyroid Carcinoma

Posted on:2017-01-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q F FuFull Text:PDF
GTID:1224330482995600Subject:Surgery
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Thyroid cancer is the most common endocrine malignancy with a rising incidence in many areas of the world. The current rise in the incidence of thyroid cancer is virtually solely from papillary thyroid cancer(PTC), which accounts for 80 to 90% of all thyroid malignancy.In recent years, the T1799 A BRAF mutation had been widely found in PTC and some anaplastic thyroid cancers. The prevalence of BRAF mutation in PTC is approximately 45%. Therefore, the BRAFV600 E mutation is a good diagnostic marker. The other tumor suppressor gene, p53, may play a critical role in promoting dedifferentiation of well differentiated PTC. Roderick et al had suggested that many ATCs with papillary components are derived from BRAF-mutated PTC, because of the addition of p53 mutation. Associated with P53 gene, serum p53 antibodies(Abs) was a kind of broad-pectrum tumor marker, which was detected in patients with various types of cancer, including PTC. BRAFV600 E mutation analysis in US-guided FNA in diagnosis may be the new approach for treatment PTC had been widely used in the world. Nevertheless, detection of BRAF mutation and serum p53 Abs were not widely used as molecular testing and serological detection for preoperative diagnosis and guiding therapeutic decision-making of PTC.to determine whether p53 antibodies could be a relevant marker for PTC,For thyroid cancer increase serum p53 antibody detection efficiency problem,we first use of P53,P53 protein shows a single epitope phage-SS phage display and phage-SP were 53 cases of thyroid tumors and 139 cases of patients with papillary thyroid carcinoma p53 antibody research. The results show, phage-SP than P53 and phage-SS has high sensitivity and specificity in the detection of papillary thyroid cancer patients serum p53 antibody respects and papillary thyroid carcinoma patients serum p53 antibody detection rate was significantly higher than the thyroid adenoma group. Further analysis found that, p53 antibody and accumulation of P53 protein has a significant positive correlation. These results indicate that serum p53 antibody may be used as a potential marker assisted papillary thyroid carcinoma clinical diagnosis and prognosis.To determine whether p53 antibodies could be a relevant marker for PTC, we prepared recombinant P53 protein and two types of fil Acrylamideentous bacteriophages for the detection of serum p53 antibodies. 53 cases with thyroid adenoma and 139 PTC patients were enrolled in this study. Compared with P53 protein and Phage-SS, phage-SP showed a higher sensitivity and specificity in the detection of serum p53 antibodies from patients with PTC, and there was a marked difference in general between the PTC group and benign control group for serum p53 antibodies. Further analysis revealed that p53 antibodies were positively associated with clinical stage, node metastasis and P53 protein accumulation. These results indicate that serum p53 antibodies could be a useful marker for PTC.To optimize the detection method for BRAFV600 E problems, the present study of 44 cases of PTC patients and 12 cases of benign pathology paraffin patients were more than three measurement methods for direct sequencing(Sanger sequencing), commonly used in clinical Realtime PCR kit reagents fluorescent probe box detection method(RT-PCR), and immunohistochemistry(BRAFV600E monoclonal antibody VE1). The results showed that, compared to the gold standard direct sequencing method, the other two methods can be detected in the tumor tissue BRAFV600 E PTC gene mutation, and greater specificity RT-PCR method, and immunohistochemistry localization better. These results indicate that the three methods can effectively detect BRAFV600 E gene mutation, but the direct sequencing detection rate is more dormpant.Meanwhile, to evaluate the diagnostic value and clinical prognostic usefulness of serum p53 antibodies(Abs) and BRAF mutation in patients with papillary thyroid carcinoma(PTC) with fine needle capillary cytology(FNCC) technique. A total of 312 patients, including 85 cases with thyroid adenoma and 227 PTC patients, were enrolled in this study. Adding BRAF test to FNCC could significantly improve sensitivity. and accuracy. Both p53 Abs and BRAF mutation were associated with lymphnode metastasis, and advanced TNM stages, and p53 Abs was positively associated with multifocality, while BRAF mutation with extrathyoidal extension respectively. Furthermore, There is a higher prevalence of extrathyoidal extension, lymphnode metastasis, multifocality and advanced TNM stages with double positive. These results indicate that serum p53 Abs and BRAF mutation in FNCC may be useful in diagnosis and guiding surgical decision making for PTC.
Keywords/Search Tags:serum p53 antibodies, BRAFV600E, phage display technology, FNCC, papillary thyroid cancer
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