Analysis Of Clinical Features And Related Factors Of Poor Prognosis In Patients With Differentiated Thyroid Carcinoma

BackgroundThyroid carcinoma is one of the most common endocrine tumors.In recent years,the incidence of the disease has been increasing rapidly worldwide.The incidence of thyroid cancer in recent decades has increased several times,especially in China,South Korea,Japan and other countries in Asia.According to the Cancer statistics in China,2015:thyroid cancer has the fastest growing rate of tumor incidence in china,and its incidence rate in 2011 has risen to the sixth place of the malignant tumors in female.Differentiated thyroid carcinoma(DTC)which consist of papillary thyroid carcinoma and follicular thyroid carcinoma are the most common pathological types of thyroid carcinoma,accounting for about 85-90%of the total.The prognosis of DTC is relatively good,the 10 year survival rate of papillary thyroid carcinoma can reach more than 95%.The clinical manifestations of differentiated thyroid carcinoma varies a lot,tumor size(the longest diameter of the tumor),whether there is an invasion out of the thyroid glands,whether there is cervical lymph node metastasis and the metastatic region,whether there is distant metastasis will all lead to different prognosis of patients.At the same time,the patient's age,gender and other factors will also affect the clinical manifestations of thyroid cancer to a certain extent.The study of the clinical features associated with thyroid cancer will help us gain a better understanding of the disease itself and contribute to better assessment and treatment of the patients.Most of the domestic studies on prognosis of thyroid cancer are still limited to retrospective analysis or short period follow-up.Yet more medical centers were expected to set up long-term follow-up of thyroid cancer databases.Only through the data analysis of long-term tracking of the large sample of post-surgical patients combined with their clinical manifestations and evaluation of their genetic changes,can finally yield the clinical characteristics and adverse prognostic factors of thyroid cancer patients in Chinese population.At the same time,there are many molecular events involved in the carcinogenesis of thyroid cancer such as the BRAF mutation,RAS mutation,RET/PTC rearrangement,TERT mutation and many other genetic alterations which lead to adverse biological behaviors such as invasion,metastasis,recurrence and radioactive iodine-refractory of thyroid carcinoma.However,there are few patients with distant metastasis of thyroid carcinoma,so it is not quite clear of the gene mutation and its mechanism involved in the distant metastasis of thyroid carcinoma.More basic researches on distant metastasis of thyroid cancer will help to further explore the underlying biological mechanisms of this undesirable behavior.Part.I Analysis of clinical features and related factors of poor prognosis in patients with differentiated thyroid carcinomaPurpose:Based on the follow-up database of differentiated thyroid cancer in our hospital,we analyzed the clinical characteristics and related factors of poor prognosis.Methods:update the long-term follow-up database of differentiated thyroid cancer patients in our hospital(the longest follow-up time of 20 years,a total of 2407 cases,including 2271 cases of thyroid papillary carcinoma,136 cases of follicular carcinoma),update the follow-up status of patients by telephone follow-up and analysis the clinical features of tumor size,invasion,lymph node metastasis and its metastasis region,distant metastasis.At the same time,the correlated factors of poor prognosis with thyroid cancer were investigated.Results:A total of 2407 patients with differentiated thyroid cancer admitted in our hospital from January 1997 to December 2011 were enrolled in this study.Among them,there were 2271 cases of papillary carcinoma and 136 cases of follicular carcinoma.There were 40 cases of death and 120 cases of recurrence.Through the analysis of the clinical data,we found that the clinical features of patients with thyroid cancer in our hospital during the 15 years have changed significantly.The mean age of onset raised from 42.6 years in 1997-2001 to 44.9 years in 2007-2011.The tumor diameter gradually decreased from 1.92cm in 1997-2011 to 1.54cm in 2007-2011 and 1.11cm in 2002-2006.The proportion of earlier T and N staging have significantly increased while the M staging remains not changed.What's more,the proportion of Patients with extrathyroid invasion decreased from 22.34%in 1997-2001 to 5.35%in 2007-2011.The poor prognosis related factors analysis showed the independent factors related to patients' death were extrathyroid invasion and AJCC staging while the independent factors related to total adverse events(recurrence,metastasis and death)were tumor size and lymph node metastasis region.Conclusions:1.the clinical features of patients with thyroid cancer in our hospital in the past 15 years have significantly changed,the newly onset patients tend to have more early staging.2.the independent factors related to patients' death were extrathyroid invasion and AJCC staging.3.the independent factors related to total adverse events(recurrence,metastasis and death)were tumor size and lymph node metastasis region.Part.? Case analysis of a Thyroid cancer patients with brain metastasesPurpose:to explore the potential genetic events that may be involved in the metastatic behavior of a patient suffered thyroid cancer with brain metastases by using genetic and pathological evaluationMethods:we conducted case analysis of a patient who received thyroidectomy in our hospital and found intracranial metastasis 6 months after,which led to the second time operation.We collected her bilateral primary tumor tissues together with the cervical metastatic lymph nodes and the intracranial metastasis.DNA extracted from these tissues were PCR amplified and sequenced,the mutation status of BRAF gene and TP53 gene were evaluated while pathological features of each part was also assessed by HE staining and immunohistochemical staining,in order to investigate the probable genetic events and its mechanism involving the metastatic behavior of thyroid carcinoma.Results:we detected that the BRAFV600E(T1799A)mutation were shared in all of the bilateral primary tumor tissues with the cervical metastatic lymph nodes and the intracranial metastasis,but mutation of the TP53 gene in the eighth exon only exists in the intracranial metastatic tissue.The immunohistochemical stain of the intracranial metastatic tissue showed positive results of TTF-1 and P53 while the P53 protein did not appeared in the thyroid primary tumor.Conclusions:1.in our case,the bilateral primary thyroid tumor,the cervical lymph nodemetastasis and intracranial metastases all carried BRAFV600E(T1799A)mutation,the P53(C13810T)mutation in the eighth exon was only detected in the brain metastatic lesions and was not found in the remaining lesions 2.our research showed that the intracranial metastatic tissue carrying BRAFV600E mutation and was TTF-1 positive which indicated it was originated from the primary thyroid carcinoma.3.The isolated TP53 mutation in the intracranial tissue suggested it may play an important role in the metastatic behavior.