Analysis Of Relevant Factors In Lymph Node Metastasis Of Papillary Thyroid Carcinoma

Objective: Papillary thyroid carcinoma (PTC) is the most common malignancy in thyroid gland as well as in the endocrine system. Its incidence was about 2-4/100000 per year but is now increasing owing to the changing of living style and eating habits. Most patients present a mass or masses in the thyroid gland with no evidence of lymph node metastasis (LNM) as the first symptom, which we called cN₀ patients. But LNM is the main metastatic way of PTC which occurred in about 10% cN₀ cases. It is now well-accepted that there are relations between LNM and prognosis of PTC which is concluded from several long term follow-up investigations. We aimed in this study to analyze the relevant factors in LNM of PTC in order to clarify its cause and pattern and to provide theoretical base on clinical prevention and treatment of LNM.Methods: The present study is divided into three parts. In part one, retrospective analysis had been done to 641 cases of PTC patients who had no evidence of LNM preoperation (cN₀ PTC). The relations between the cervicocentral compartment LNM and the patients' gender, age, the tumors' size, and number were considered. 114 cases were followed-up for the cervicolateral compartment lymph node recurrence. In part two, mRNA was extracted from the tissues. Then microarray technique was used to compare the different levels of genes expression in PTC with LNM. Several differentially expressed genes had been screened out. In part three, immunohistochemistry stain and hybridization in situ were used to test the decorin which was screened out by microarray analysis in groups of normal thyroid tissue, PTC with central node negative, PTC with central node positive and PTC with lateral neck positive.Results: 1. In 641 cN₀ PTC patients, the positive rate of cervicocentral compartment lymph node was 53.0% in total with 34.3% cases had no less than two nodes positive and 18.7% cases had all sampled node positive. The positive rate was 47.8%, 71.0%, and 96.0% for tumors of T1, T2, and T3 stage, respectively; 50.9% and 62.7% for tumors of monofocal lesion and multifocal lesion, respectively; 59.7% for men and 51.4% for women. The average age of the positive group was 41.86±11.09 years and was 46.62±11.34 years for the negative group. Twelve cases had occurred neck recurrence during follow-up. Among them, 11 cases had central node positive in their primary operations and the positive nodes were no less than two and 3 cases had all sampled nodes positive. 2. There were several differentially expressed gene fragments between the two groups in which the down-regulation of decorin, cullin-5, RAB15, etc. and the up-regulation of Ras-C, EVA1, SBLF, SPAP-A1, etc. were of great significance. 3. By means of integrated optical density (IOD) value, the results of immunohistochemistry stain for decorin were 87.24±9.81, 92.59±10.71, 118.73±24.59, and 134.18±16.23 for normal control group, central node negative group, central node positive group and lateral neck positive group, respectively. By means of positive cell percentage, the results of hybridization in situ were 69.21±12.82,65.47±10.98,43.45±18.66,37.12±5.66 for the four groups, respectively.Conclusions: LNM of PTC is the outcome of multiple causes involved. Young patients, tumors of high T stage and multifocal lesions are risks for cN₀ PTC to develop cervicocentral compartment LNM. The larger number of positive nodes in central compartment maybe comes to the higher risks of neck recurrence. There are several differentially expressed genes related to the LNM of PTC, in which the changing expression of decorin had confirmed significance.