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Study On BRAF Gene Mutation Analysis And Early Warning Signal Of Hashimoto’s Thyroiditis With Multifocal Papillary Thyroid Carcinoma

Posted on:2017-03-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:S DongFull Text:PDF
GTID:1224330488491934Subject:Clinical medicine
Abstract/Summary:PDF Full Text Request
Background and purpose:Hashimoto’s thyroiditis (HT) to cancer is a research hotspot in recent years, many mechanisms are still not clear, and the treatment scheme of controversial. In the past that Hashimoto’s thyroiditis is benign lesions and can cause hypothyroidism and therefore not suitable for surgery, but in recent years, found that HT for precancerous lesions, such as aggressive surgery is required for signs of cancer. Hashimoto’s thyroiditis cause cancer incidence rate has increased from 23% in the past to 58.3% in recent years, so Hashimoto’s thyroiditis and carcinogenesis have very large relationship has been reported. In recent years, the incidence of thyroid cancer in HT is increasing, especially in HT and Papillary thyroid carcinoma (PTC), and it is often associated with multiple foci of PTC. Such as HT with multiple foci of cancer should be treated with total thyroidectomy, but there is no clear indicator of HT with a single or multiple foci of cancer. Intraoperative frozen section is often left out of small cancer foci, only the routine pathological examination of the totle thyroid gland to determine whether there is a multifocal carcinoma, but it can make a low-risk single cancer patient received over treatment, and increase the incidence of postoperative complications. Therefore, it is important to study the early warning signal of HT and to guide clinical treatment.Methods:1. From June 2013 to June 2008,808 cases of HT with PTC and HT were retrospectively analyzed, including 206 males and 602 females, and the patients were treated by medical color Doppler ultrasound. All with thyroid surgery indications, surgical treatment and postoperative pathology for HT with PTC or simple HT patients were enrolled, but to exclude hyperthyroidism and subacute thyroiditis history or other malignancy, low immune function and other major disease history of cases, all patients had no history of tuberculosis and preoperative were not chemotherapy, radiotherapy and no immune treatment history. According to the postoperative pathological results, it was divided into 3 groups:A group (HT with multifocal carcinoma), B group (HT with single carcinoma), C group (single HT). The results were compared with the conventional pathological results and TPOAb test results before and after operation. The postoperative pathological results were compared with the preoperative patients and TSH results. The correlation between the analysis and single cancer, multiple foci of cancer and the correlation with lymph node metastasis.2. In our hospital from June 2012 to 2014 June thyroid surgery in patients with postoperative pathological diagnosis, HT (n=30) and HT single carcinoma(n=30) and HT multifocal carcinoma(n=30) cases of pathological specimens made of paraffin slice a total of 90 cases. All cases were confirmed by pathological diagnosis, and no history of chemotherapy, radiotherapy and immunotherapy was performed. The paraffin blocks were sliced by requirement, and the immunohistochemical tests about CK-19, COX2, Galectin-3 and HBME-lwere performed.3. In our hospital from June 2012 to 2014 June thyroid surgery in patients with postoperative pathological diagnosis, HT (n=10) and HT single carcinoma (n=40) and HT multifocal carcinoma (n=30) cases of pathological specimens made of paraffin slice for DNA extraction, and then PCR assay for detection of BRAF gene mutation.Results:1.232 cases of HT combined with multifocal PTC in 196 patients with TPOAb were significantly elevated>1300 IU/mL; in addition,469 patients with HT combined with single PTC in 416 patients with<1000 IU/mL TPOAb (most of the 400-600); the remaining 107 patients with TPOAb were significantly different; TPOAb index in HT patients with HT combined single and multiple PTC patients were significantly different (P<0.01).2. The expression of C group was lowest, and the difference was significant (P<0.05). CK19:Group A was significantly higher than that in group B, with significant difference (P<0.05). COX-2:There was no significant difference between A group and B group (P>0.05). Galectin-3:There was no significant difference between A group and B group (P>0.05). HBME-1:There was no significant difference between A group and B group (P>0.05). CK19 immunochemistry assay showed that if the mean density>0.007, there is the greatest difference between the two groups(A and B) (P<0.001), it can be used as a distinction between HT with single PTC and multiple PTC.3. The BRAF gene mutation in A group was significantly higher than that in B group, while the C group had no BRAF gene mutation, and the BRAF gene mutation was 29.63% in A group, and 10.26% in B group, which had a significant difference (P< 0.05).Conclusion:1. TPOAb>1300IU/mL is a high risk factor for HT combined with multifocal PTC, The intraoperative frozen pathology report for HT combined with PTC (TPOAb>1300 IU/mL) was recommended for patients with totle thyroidectomy. However, the increase of TSH with TPOAb<1300 IU/mLwas not a risk factor for HT with multiple foci of PTC, and increased TSH was only used as a reference factor. In HT with multifocal PTC TPOAb index level of central neck lymph node metastasis positive rate had no effect, but multifocal cancer than single cancer metastasis positive rate is high, so no matter level of TPOAb indicators suggest central lymph node dissection.2. Only the positive expression of CK19 in A group was significantly higher than that in B group, there were significant differences, and the other indicators were not significantly different. Such as preoperative or intraoperative CK19 immunohistochemical density>0.007 is likely to be HT with multiple foci of cancer, can be recommended for totle thyroidectomy combined with Intraoperative frozen section.3. The mutation rate of BRAF gene in HT with multifocal PTC was significantly higher than that of HT with single PTC. If it is detected that there is a mutation of BRAF gene, it may be HT with multifocal PTC, can be recommended for totle thyroidectomy combined with Intraoperative frozen section.
Keywords/Search Tags:Hashimoto’s thyroiditis, papillary thyroid carcinoma, TPOAb, BRAF
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