Relevant Research Between Ultrasonic Imaging And Osteopontin Expression, Microvessel Density Determination In Thyroid Cancer

BackgroundThyroid cancer is common head and neck malignancies, in recent years, the disease incidence rate had the trend of escalation, the early-time thyroid cancer excised after the surgery, nearly may permanently cure, but the later-period thyroid cancer will have distant place shifts , such as lymph nodes, lungs, bone and other distant metastasis, early diagnosis, early treatment is essential. At present, the clinical diagnosis of thyroid cancer mainly depends on palpation and imaging (high-frequency ultrasound, radionuclide, CT, MRI) and immunoassay, etc, color Doppler ultrasound is currently the most important means of inspection for the thyroid and neck disease, with the development of ultrasound imaging and the application of new technologies, ultrasound can observe the minimal disease of 2-3mm ,and more clearly show the internal structure of nodules, with or without capsule and small structures such as micro-calcification changes, as well as color Doppler signals and Doppler changes in the spectrum, have provided favorable conditions to improve the diagnostic rate of thyroid disease. However, due to different types of pathological thyroid nodules, large differences in biological characteristics, and with multiple and multi-derived characteristics, ultrasonic performance of some nodules is not typical, there are difficulties in diagnosis, and there is a certain proportion of the missed diagnosis and misdiagnosis in the ultrasound examination, differential diagnosis of some benign and malignant nodules still controversial.ObjectiveBy observing the color Doppler ultrasonography performance of 145 cases of thyroid nodules confirmed by surgery and pathology , carried on the single factor and the multi-factor analysis, to obtain the most relevant ultrasonographic features for the diagnosis of thyroid cancer ,to provide a theoretical basis for identifying benign and malignant thyroid nodules easily.MethodsSelected 145 cases of thyroid nodules admitting to our hospital general surgical department from June 2006 to August 2008. all patients were preoperatively with color Doppler ultrasonography, careful observation and recording of two-dimensional and color Doppler ultrasonic performance of lesions was made, including lesion number, size, border, internal echo, sand-like strong echoes, halo sound, rear attenuation, flow classification , flow resistance index,and neck lymph node swelling. After operation and pathology comparison, carried on the single factor and the Logistic multi-factor regression analysis, screened the thyroid cancer related ultrasonic characteristics.Results145 cases of thyroid nodules, including 48 cases of papillary carcinoma, 6 cases of follicular carcinoma, 2 cases of medullary carcinoma, 1 cases of metastatic carcinoma; 69 cases of nodular goiter, 19 cases of thyroid adenoma.88 cases of benign thyroid nodules, 8 cases (9.1%)with fuzzy borders, low-echo 26cases (29.5%), 4 cases with sand-like strong echo (4.5%), 6 cases with rear attenuation (6.8%),5 cases with blood flow RI> 0.7 (5.7%); 57 cases of thyroid cancer , with fuzzy boundaries 39(68.4%); hypoechoic cases 46(80.7%), with sand-like strong echo 35cases (61.4%),21 cases with rear attenuation (36.8%),19cases with flow RI> 0.7 (33.3% ).23 cases with lymph node metastasis (40.4%). Swollen lymph nodes in the middle neck were 76% (19/25). Metastatic lymph nodes showed increasing and round, cortical thickening and medullary eccentric or disappear, internal echogenic heterogeneous, sand-like strong echoes, varying degrees of cystic change, blood flow increasing and disorder.By single factor analysis, to diagnosis the thyroid cancer meaningful ultrasonic characteristics including single lesion. fuzzy border, low-echo, sand-like strong echoes, rear attenuation, high blood flow resistance and neck lymph node swelling.By Logistic regression analysis, thyroid cancer associated sonographic characteristics including: single lesion ,sand-like strong echoes, hypoechoic, and boundary ambiguity. Conclusions1. Multi-factor Logistic regression analysis showed that, the related factors for diagnosis of thyroid cancer includes: single lesion ,sand-like strong echoes (microcalcification), low echo, and boundary ambiguity.2. Lymph node metastasis of thyroid cancer often was multi-division transfer, III District (in the middle neck) as the most common metastatic sites; the main ultrasonic features included: lymph nodes increased, round, corticomedullary demarcation, lymph gate structure destroyed or disappeared; lymph internal echo heterogeneous, and sometimes may appear sand-like strong echoes; some cystic changes occur within lymph nodes.3. Color Doppler ultrasound is of great significance in the differential diagnosis of benign and malignant thyroid nodules , can provide accurate information for the clinical diagnosis and treatment.PART TWO Expression of osteopontin in thyroid papillary carcinoma and its relationship with ultrasonographic features.BackgroundThyroid cancer is common head and neck malignancies, in recent years, the disease incidence rate had the trend of escalation, of all thyroid malignancies papillary thyroid carcinoma accounts for more than 75 percent, and its pathogenesis and biological processes are not yet completely clear. Osteopontin (OPN) is a calcium-binding secreted phosphorylated glycoprotein containing specific RGD- sequence, with the promotion of cell chemotaxis, adhesion and migration functions. At present, OPN has been reported in the breast, colon, stomach, liver, ovarian cancer and other malignant tumors with high expression,but in head and neck cancer (including thyroid cancer) reported rare. In this paper, by studying expression of OPN in papillary thyroid carcinoma and investigating the relationship between expression of OPN and ultrasonic performance of papillary thyroid carcinoma, to study the molecular mechanisms of papillary thyroid cancer ,and to evaluate the biological behavior and prognosis of the tumor.ObjectiveTo investigate the expression of osteopontin(OPN) in human thyroid papillary carcinoma and its relationship with ultrasonographic features.MethodsUltrasonographic scanning was performed in 48 patients with thyroid papillary carcinoma before operation, ultrasonographic features were analyzed. The 48 specimens were collected, the expressions of OPN mRNA and protein were analyzed by using FQ - PCR and immunohistochemical staining respectively. 30 samples of thyroid benign lesions and 20 samples of normal thyroid tissues were selected as control group. Results of OPN expressions were compared with ultrasonographic features.ResultsThe expression levels of OPN mRNA and protein in thyroid papillary carcinoma were higher than those of control. Expression of OPN was significant related with the presence of microcalcification in ultrasonography,the expression of OPN in microcalcification group was higher than that in non-microcalcification group. The expression of OPN in the group with lymph nodes metastasis was higher than that in the group without lymph nodes metastasis. No significant relevance was found between the expression of OPN and other ultrasonographic features(include tumor size, margin and blood flow).ConclusionsThe expression levels of OPN in thyroid papillary carcinoma were higher than that in benign lesions and normal thyroid tissues. OPN may play an important role in the development of thyroid papillary carcinoma ; The expression levels of OPN mRNA was related with the presence of microcalcification and lymph nodes metastasis in ultrasonography. OPN may take part in the formation of the microcalcification, the ultrasonographic features can reflect the expression of OPN, so the biological behavior and prognosis of thyroid papillary carcinoma can be assessed by ultrasonographic features to some extent. PART THREE Microvessel Density Determination in Thyroid Papillary Carcinoma and its Relationship with Ultrasonographic Features.BackgroundTumor angiogenesis plays an important role in its growth, invasion and metastasis, studying tumor angiogenesis in cancer research has been hot, measuring microvessel density (MVD) is now commonly used in evaluation of tumor angiogenesis, MVD can precisely reflect the angiogenesis in the tumor, has been regarded as an independent indicator for prediction of tumor prognosis. At present,in the majority of solid tumors , MVD was significantly increased and related to their invasiveness. CD34 is a new type of microvascular markers, which shows the vascular endothelial cells, the more sensitivity and specificity, ease of observation, with anti-CD34 antibody for microvessel staining can provide more useful and reliable information than the other markers.At present, with the extensive use of ultrasonography ,color Doppler ultrasound has become one of the main inspection means for clinical diagnosis of thyroid disease, on the differential diagnosis of benign and malignant nodules has accumulated certain experience, but in some aspects of differential diagnosis of nodules is still controversial. In recent years , determination of MVD provides a new direction for the development of technology in thyroid nodular disease diagnosis, MVD accurately identifies tumor microvessel, and ultrasonic blood flow classification is the distribution of tumor blood vessels within the macro-test assessment, This study was to investigate the intrinsic link between the two ,and to provide more useful information for clinical diagnosis and assessment.ObjectiveThrough the observation of two-dimensional and color Doppler ultrasonography of 48 cases of papillary thyroid carcinoma and the control group, determination of MVD, compared with pathological results, evaluated color Doppler ultrasound and determination of MVD in the diagnosis of papillary thyroid carcinoma.MethodsColor Doppler ultrasonic examination Using ATL HDI-5000 and GE LOGIQ 9 color ultrasound diagnostic apparatus , observed and recorded the ultrasonography of 48 cases of papillary thyroid carcinoma. Two-dimensional ultrasonic observation of thyroid nodules included location, size, number, boundaries (fuzzy or clear), internal echo ,calcification (with particular attention to the existence of microcalcifications), neck lymph node swelling, and so on. Using color Doppler flow imaging (CDFI) and power Doppler imaging(PDI) to detect blood flow in each nodule, the nodule internal flow was divided into 4 levels(0-III) according to the Alder semi-quantitative methods.Determination of MVDWith anti-CD34 monoclonal antibodies for immunohistochemical staining to detect the MVD in 48 cases of papillary thyroid carcinoma, 30 cases of benign thyroid lesions and 20 cases of normal thyroid tissue, made the capillaries counting in 200 time of fields (0.739mm~2) by two counters for each specimen for microvessel count using double-blind method, took the two's mean value for one specimen.ResultsUltrasonic performance of Papillary thyroid carcinoma Papillary thyroid carcinoma in this group the most common sonographic performance showed irregular hypoechoic nodules, and nodules with fuzzy boundary , non-homogeneous and cluster "sand-like" strong echo, more than one strip flow points in the majority of nodules, often accompanied by lymph node metastasis. The flow in the nodules is divided into 4 levels according to the Alder semi-quantitative method, grade 0 9 cases , grade I 13 cases , grade II -III 26 cases.MVD in benign and malignant thyroid nodulesMVD of papillary thyroid cancer tissue (126.8±42.1) is higher than that of benign thyroid lesions (95.2±38.5) and normal thyroid tissue (83.7±27.6)(p<0.05). The difference of MVD between benign thyroid lesions and normal thyroid tissue has no significances.Papillary thyroid carcinoma power Doppler grading vs MVDMean MVD were: 97.3±35.4 (grade 0), 104.6±30.8 (grade I), 127.5±43.0 (grade II), 141.3±37.2 (grade III). By analysis of variance at all levels ,the numerical differences were significant (p<0.05),grade II was significantly higher than grade 0 and I, grade III were significantly higher than grade II, with the flow classification increased MVD was significantly higher.Correlation between MVD and lymph node metastasisMVD in lymph node metastasis positive group was 140.3±44.5, lymph node negative group was 116.0±36.7,by t-test, the difference between the two groups was statistically significant (p<0.05),showed that the MVD in papillary thyroid carcinoma lymph node metastasis positive group was higher than that of the negative group.Correlation between papillary thyroid carcinoma sonographic features and MVDMVD of 22 Larger nodules (≥2cm) was 139.4±37.8, 26 smaller nodules (<2cm) was 117.5±43.3, difference between the two groups was statistically significant (P<0.05), showed that larger nodules had higher MVD than smaller nodules. Nodular borders and gravel-like calcification were not significantly associated with MVD.Conclusions1. MVD of papillary thyroid carcinoma was higher than that of benign lesions and normal thyroid tissue.2. Of ultrasonic features , the nodule size and lymph node metastasis were related to MVD significantly. The application of color Doppler Imaging accurately reflect the tumor microvessel situation.3. Color Doppler ultrasound combined with the MVD determination will be able to more accurately reflect the tumor blood supply situation, and provide more information for clinical diagnosis and assessment.