Lymph Node Metastasis In Papillary Thyroid Carcinoma Patients Research Articles

Diagnostic value of contrast-enhanced ultrasonography in the preoperative evaluation of lymph node metastasis in papillary thyroid carcinoma: a single-center retrospective study

BackgroundContrast-enhanced ultrasound (CEUS) has been recently used for the assessment of cervical lymph node metastasis (LNM) to guide surgical operation in patients with papillary thyroid carcinoma (PTC). However, the specificity and sensitivity of CEUS reported from previous studies are not consistent. The objective of this study was to evaluate the diagnostic value of CEUS for the metastasis of cervical lymph nodes in PTC patients based on data from one regional central hospital.MethodsThe diagnostic value of CEUS in preoperative LNM of PTC patients was concluded by comparing the results of CEUS on lymph node status with postoperative pathology examination. In addition, this study conducted hierarchical analysis of PTC patients to explore whether tumor size, different lymph node regions, and Hashimoto’s thyroiditis influence the assessment of CEUS.ResultsThis research study ultimately enrolled 965 PTC patients, including 266 males and 699 females with a mean age of 42.27 ± 11.34 years. A total of 527 patients were considered clinical-node negative, and 438 were clinical-node positive before surgery. The specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of CEUS in the assessment of LNM in PTC patients were 56.00%, 71.00%, 57.06%, 69.76% and 62.59%, respectively. For central and lateral lymph nodes, the accuracy of CEUS in PTC patients was 49.43% and 54.30%, respectively. In addition, it was shown that the accuracy of CEUS in PTC patients with Hashimoto’s thyroiditis (HT) slightly decreased to 58.44%, and the accuracy of CEUS in PTC patients with non-HT in turn increased to 64.17%. The accuracy of CEUS in non-papillary thyroid microcarcinoma (PTMC) and PTMC patients was 65.68% and 61.24%, respectively. The accuracy of CEUS in predicting central LNM was significantly different between PTC patients with or without HT (P < 0.001) in this study but not for lateral lymph nodes (P = 0.114).ConclusionThe accuracy of CEUS in the assessment of LNM in PTC is not consistently satisfactory, especially for central lymph nodes, small tumor diameters, or patients with HT. More diagnostic technologies for abnormal lymph nodes should be considered in PTC patients.

Impaired thyroid hormone sensitivity increases the risk of papillary thyroid cancer and cervical lymph node metastasis.

The association of thyroid hormone sensitivity with papillary thyroid carcinoma (PTC) is unclear. This study investigated the relationship between the thyroid hormone sensitivity indices and the risk of PTC and the influence of thyroid hormone sensitivity on the aggressive clinicopathologic features of PTC. This retrospective study recruited 1225 PTC patients and 369 patients with benign nodules undergoing surgery in Zhongshan Hospital in 2020. The thyroid hormone sensitivity indices were thyroid feedback quantile-based index (TFQI), TSH index (TSHI) and thyrotropin thyroxine resistance index (TT4RI). We employed logistic regression models to explore the correlation between the thyroid hormone sensitivity indices and the risk of PTC and its cervical lymph node metastasis (LNM). PTC patients had significantly higher levels of TSH, TFQI, TSHI and TT4RI compared to the patients with benign nodules, but thyroid hormone levels did not differ significantly between the two groups. Logistic regression analysis revealed that the higher levels of TFQI, TSHI, and TT4RI were associated with an increased risk of PTC after adjustment for multiple risk factors (TFQI: OR = 1.92, 95% CI: 1.39-2.65, P < 0.001; TSHI: OR = 2.33, 95% CI:1.67-3.26, P < 0.001; TT4RI: OR = 2.41, 95% CI:1.73-3.36, P < 0.001). In addition, patients with decreased thyroid hormone sensitivity had a higher risk of cervical LNM in multiple logistic regression analysis (TFQI: OR = 1.38, 95% CI:1.03-1.86, P = 0.03; TSHI: OR = 1.37, 95% CI:1.02-1.84, P = 0.04; TT4RI: OR = 1.41, 95% CI:1.05-1.89, P = 0.02). Impaired sensitivity to thyroid hormone was associated with an increased risk of PTC, and it is also associated with a higher risk of cervical LNM in PTC patients.

Risk factors of occult lymph node metastasis of levels Ⅲ and Ⅳ in papillary thyroid carcinoma

Objective: To investigate the potential risk factors for occult lateral cervical lymph node metastasis (LNM) to levels Ⅲ and Ⅳ in patients with papillary thyroid carcinoma (PTC) and the necessity of super-selective lateral lymph node dissection for patients harboring these metastases. Methods: This prospective study included PTC patients who were operated by the same surgeon in the Department of Head and Neck Surgery of Cancer Hospital, Chinese Academy of Medical Sciences from October 2015 through October 2019. Preoperative ultrasound and enhanced Computer Tomography (CT) did not denote suspected enlarged lymph nodes in the lateral neck. All patients underwent lymph node dissection in levels Ⅲ and Ⅳ on the basis of original thyroid collar incision after LNM to level Ⅵ was confirmed by preoperative fine needlebiopsy or intraoperative frozen pathology. Results: Of all 143 patients, 74 (51.7%) had occult LNM in levels Ⅲ and Ⅳ confirmed by postoperative pathology. The average number of metastasized lymph nodes in levels Ⅲ and Ⅳ was 2.64±1.80, and that in level Ⅵ was 3.77±3.27. There was a significant linear positive correlation between the number of metastasized lymph nodes in level Ⅵ and that in levels Ⅲ and Ⅳ (r=0.341, P<0.001). That the metastasized lymph nodes in level Ⅵ equals three was the best predictor of occult lateral LNM to levels Ⅲ and Ⅳ. Univariate analysis showed that age <55 years, tumor size ≥2.0 cm, number of metastasized lymph nodes in level Ⅵ ≥3, and percentage of metastasized lymph nodes in the total number of dissected lymph nodes in level Ⅵ >50% were associated with occult LNM in levels Ⅲ and Ⅳ (P<0.05). Multivariate analysis showed that number of metastasized lymph nodes in level Ⅵ≥3 was an independent risk factor for occult LNM in levels Ⅲ and Ⅳ (P=0.006). Conclusions: Age, tumor size and LNM in level Ⅵ were associated with occult lateral LNM in PTC patients. Lymph node dissection in levels Ⅲ and Ⅳ could be considered for selective patients, since it will help to avoid secondary operation for residual tumor or recurrence resulted from insufficient treatment without increasing the incidence of complications or affecting patients' appearances.

A radiomics nomogram for the ultrasound-based evaluation of central cervical lymph node metastasis in papillary thyroid carcinoma.

To develop and validate a radiomics nomogram based on ultrasound (US) to predict central cervical lymph node (LN) metastasis in patients with papillary thyroid carcinoma (PTC). PTC patients with pathologically confirmed presence or absence of central cervical LN metastasis in our hospital between March 2021 and November 2021 were enrolled as the training cohort. Radiomics features were extracted from the preoperative US images, and a radiomics signature was constructed. Univariate and multivariate logistic regression analyses were used to screen out the independent risk factors, and a radiomics nomogram was established. The performance of the model was verified in the independent test cohort of PTC patients who underwent thyroidectomy and cervical LN dissection in our hospital from December 2021 to March 2022. In the independent test cohort, the radiomics model based on long-axis cross-section and short-axis cross-section images outperformed the radiomics models based on either one of these sections (the area under the curve (AUC), 0.69 vs. 0.62 and 0.66). The radiomics signature consisted of 4 selected features. The US radiomics nomogram included the radiomics signature, age, gender, BRAF V600E mutation status, and extrathyroidal extension (ETE) status. In the independent test cohort, the AUC of the receiver operating curve(ROC) of this nomogram was 0.76, outperformingthe clinical model and the radiomics model (0.63 and 0.69, respectively), and also much better than preoperative US examination (AUC, 0.60). Decision curve analysis indicated that the radiomics nomogram was clinically useful. This study presents an efficient and useful US radiomics nomogram that can provide comprehensive information to assist clinicians in the individualized preoperative prediction of central cervical LN metastasis in PTC patients.

Nomogram model based on preoperative serum thyroglobulin and clinical characteristics of papillary thyroid carcinoma to predict cervical lymph node metastasis

ObjectivePreoperative evaluation of cervical lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) has been one of the serious clinical challenges. The present study aims at understanding the relationship between preoperative serum thyroglobulin (PS-Tg) and LNM and intends to establish nomogram models to predict cervical LNM.MethodsThe data of 1,324 PTC patients were retrospectively collected and randomly divided into training cohort (n = 993) and validation cohort (n = 331). Univariate and multivariate logistic regression analyses were performed to determine the risk factors of central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM). The nomogram models were constructed and further evaluated by 1,000 resampling bootstrap analyses. The receiver operating characteristic curve (ROC curve), calibration curve, and decision curve analysis (DCA) of the nomogram models were carried out for the training, validation, and external validation cohorts.ResultsAnalyses revealed that age, male, maximum tumor size >1 cm, PS-Tg ≥31.650 ng/ml, extrathyroidal extension (ETE), and multifocality were the significant risk factors for CLNM in PTC patients. Similarly, such factors as maximum tumor size >1 cm, PS-Tg ≥30.175 ng/ml, CLNM positive, ETE, and multifocality were significantly related to LLNM. Two nomogram models predicting the risk of CLNM and LLNM were established with a favorable C-index of 0.801 and 0.911, respectively. Both nomogram models demonstrated good calibration and clinical benefits in the training and validation cohorts.ConclusionPS-Tg level is an independent risk factor for both CLNM and LLNM. The nomogram based on PS-Tg and other clinical characteristics are effective for predicting cervical LNM in PTC patients.

Evaluation of plasma exosomal miRNAs as potential diagnostic biomarkers of lymph node metastasis in papillary thyroid carcinoma.

The early diagnosis of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) is clinically important, as it can aid in treatment decision-making and improve prognosis. In the present study, we aimed to identify whether plasma exosomal miRNAs could be potential diagnostic markers of LNM in PTC. Profiles of plasma exosomal miRNAs were screened using miRNA microarrays. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed in the validation and diagnostic sets to select candidate exosomal miRNAs. Finally, receiver operating characteristic (ROC) curves were generated to evaluate the efficiency of target exosomal miRNAs in distinguishing PTC-N1 patients from PTC-N0 patients. In total, 197 miRNAs were found to be differentially expressed in the testing set. Based on the qRT-PCR results, the expression of miR-6774-3p (p < 0.001) and miR-6879-5p (p < 0.001) in the PTC-N1 patients was significantly higher than that in the controls. The AUC values of plasma exosomal miR-6774-3p (0.802; 95% CI, 0.724-0.879) and miR-6879-5p (0.787; 95% CI, 0.706-0.867) and their combination (0.914; 95% CI, 0.865-0.962) were higher than those of the total miRNAs directly isolated from plasma. Moreover, the expression of exosomal miRNAs was stable after treatment with RNase A, prolonged incubation, or repeated freezing and thawing. The two plasma exosomal miRNAs (miR-6774-3p and miR-6879-5p) and their combination could serve as new promising biomarkers for the diagnosis of LNM in PTC patients.

Development and validation of a novel 14-gene signature for predicting lymph node metastasis in papillary thyroid carcinoma.

There is still no reasonably accurate method of preoperatively predicting central lymph node metastasis (LNM), and it is essential to develop an effective evaluation model for predicting LNM in papillary thyroid carcinoma (PTC) patients. PTC samples were collected from The Cancer Genome Atlas database. Candidate genes were identified as continuously upregulated or downregulated genes in the process of N0 to N1a and N1a to N1b. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct the predictive model for LNM. Multivariate logistic regression analysis was performed to screen the potential factors related to LNM, and a nomogram was established. The risk score of the gene signature model for predicting disease-free survival (DFS) was evaluated by Kaplan-Meier analysis. A 14-gene signature was developed by LASSO regression for predicting LNM based on 69 differential expression genes (DEGs) that were continuously upregulated or downregulated in the progress of PTC. The receiver operating characteristic (ROC) curves of the 14-gene signature predicting LNM, central LNM and lateral LNM were generated. The area under the ROC (AUC) values were 0.806 [95% confidence interval (CI): 0.7608-0.8815], 0.755 (95% CI: 0.6839-0.8263) and 0.821 (95% CI: 0.7608-0.8815). The nomogram's C-index value, including the 14-gene signature and other potential risk factors, was 0.786 (95% CI: 0.7296-0.8425), and the calibration exhibited fairly good consistency with the perfect prediction. Based on the 14-gene risk score, high-risk PTC patients had a worse DFS. A novel 14-gene signature was developed for predicting LNM in PTC patients. The risk score also correlated with DFS in PTC patients.

Dysregulation of microRNAs as the risk factor of lymph node metastasis in papillary thyroid carcinoma: systematic review.

Papillary thyroid carcinoma (PTC) has an excellent prognosis with a relatively low mortality rate, but a small portion of PTC patients suffer from an aggressive form of the disease. In such cases early detection of lymph node metastasis (LNM) is as paramount as it is problematic. The routine use of central neck lymph node dissection is not recommended. New methods to detect LNM are needed. MicroRNAs are a potential biomarker for diagnosis and prognosis of PTC. In this review we summarise the current knowledge regarding dysregulated miRNAs and their association with LNM in PTS patients. The PubMed and EBSCO databases were searched using terms for "microRNA", "thyroid carcinoma", and "prognosis" by using Boolean operators. Based on eligibility and exclusion criteria, articles were screened and reviewed in full, methodological data of included studies were extracted, and risk of bias analysis performed. In total, 446 unique studies were extracted from the mentioned databases, and based on inclusion and exclusion criteria 27 studies were included in this review. Of them 17 analysed tissue microRNAs, 5 analysed circulating microRNAs, and 5 studies analysed both tissue and circulating samples. MiRNA-146B, miRNA-221, miRNA-222, miRNA-21, miRNA-204, miRNA-451, miRNA-199a-3p, and miRNA-30a-3p were dysregulated in at least 2 separate studies. A sizable portion of studies failed to show statistically significant differences in miRNA expression between LNM-positive and -negative patients. Different methodologies and disparities of patient populations could explain these discrepancies.\ This research supports the statement that specific up- and downregulated miRNAs are associated with LNM in PTC patients. However, the prognostic value of these miRNAs is limited. Additional targeted cohort studies are required to elucidate the role of miRNAs in defining individualised treatment strategies for thyroid cancer patients.

Lymph node metastasis prediction of papillary thyroid carcinoma based on transfer learning radiomics

Non-invasive assessment of the risk of lymph node metastasis (LNM) in patients with papillary thyroid carcinoma (PTC) is of great value for the treatment option selection. The purpose of this paper is to develop a transfer learning radiomics (TLR) model for preoperative prediction of LNM in PTC patients in a multicenter, cross-machine, multi-operator scenario. Here we report the TLR model produces a stable LNM prediction. In the experiments of cross-validation and independent testing of the main cohort according to diagnostic time, machine, and operator, the TLR achieves an average area under the curve (AUC) of 0.90. In the other two independent cohorts, TLR also achieves 0.93 AUC, and this performance is statistically better than the other three methods according to Delong test. Decision curve analysis also proves that the TLR model brings more benefit to PTC patients than other methods.

A nomogram model based on the preoperative clinical characteristics of papillary thyroid carcinoma with Hashimoto's thyroiditis to predict central lymph node metastasis.

Preoperative prediction of central lymph node (LN) metastasis in papillary thyroid carcinoma (PTC) with Hashimoto's thyroiditis (HT) provides an important basis for surgical decision-making, especially regarding the extent of tumour resection. We aimed to develop and validate a nomogram model for the preoperative assessment of central LN metastasis. We retrospectively collected the data of 994 PTC patients with HT who underwent surgery at the West China Hospital from January 2008 to December 2017. Among them, 606 patients who underwent surgeries relatively earlier comprised the training cohort for nomogram development, while the other 388 who underwent surgeries relatively later formed the validation cohort to validate the model's performance. Univariate and multivariate logistic regression analyses were conducted using the data of the two respective cohorts, as well as the data of the combined cohort. The relevant preoperative potential risk factors include demographic characteristics, medical history information, thyroid function test, ultrasound characteristics and BRAF V600E gene detection. A nomogram model was subsequently developed. The performance, discrimination and calibration of the nomogram model were assessed in the training and validation cohorts and in the combined cohort. The central LN metastasis rate of PTC with HT was 49.7% (301/606) and 48.7% (193/388) in the training and validation cohorts, respectively. The univariate and multivariate logistic regression analyses indicated that younger age, normal body mass index, BRAF V600E mutation, larger maximum diameter, left lobe tumour, aspect ratio >1, capsular invasion and calcification were significant risk factors for central LN metastasis in PTC patients with HT. The preoperative nomogram showed good calibration and discrimination for the training and validation cohorts, as well as for the combined data set. The nomogram we developed and validated with a comprehensive set of preoperative factors is effective in predicting central LN metastasis in PTC patients with HT.

Ultrasound-Based Radiomic Nomogram for Predicting Lateral Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma

Accurate preoperative identification of lateral cervical lymph node metastasis (LNM) is important for decision-making and clinical management of patients with papillary thyroid carcinoma (PTC). The aim of this study was to develop an ultrasound (US)-based radiomic nomogram to preoperatively predict the lateral LNM in PTC patients. In this retrospective study, a total of 886 patients were enrolled and randomly divided into 2 groups. Radiomic features were extracted from the preoperative US images. A radiomic signature was constructed using the least absolute shrinkage and selection operator algorithm in the training set. Multivariate logistic regression was performed to develop the radiomic nomogram, which incorporating the radiomic signature and the selected clinical characteristics. The performance of the nomogram was assessed by its discrimination, calibration, and clinical usefulness in both the training and validation sets. The radiomic signature was significantly associated with the lateral LNM in both cohorts (p< 0.001). The nomogram that consisted of radiomic signature, US-reported cervical lymph node (CLN) status, and CT-reported CLN status demonstrated good discrimination and calibration in the training and validation sets with an AUC of 0.946 and 0.914, respectively. The decision curve analysis indicated that the radiomic nomogram was worthy of clinical application. The radiomic nomogram proposed here has good performance for noninvasively predicting the lateral LNM and might be used to facilitate clinical decision-making and potentially improve the survival outcome in selected patients.

IGFBP3 as an indicator of lymph node metastasis and unfavorable prognosis for papillary thyroid carcinoma

Lymph node metastasis (LNM) is a usual event in papillary thyroid carcinoma (PTC) patients, which usually leads to poor prognosis. However, the molecular mechanisms of LNM remain unclear. Thus, we aimed to screen the possible key genes in the progression of LNM in PTC patients and further validate their roles. The study involved two phases: a discovery phase and a validation one. In the former phase, the candidate genes were screened by using bioinformatics methods. In the latter one, the genes were firstly assessed in a cohort from the cancer genome atlas (TCGA) to evaluate the associations of their expressions with clinical features and the prognostic values, and then, they were assessed at protein levels by using an immunohistochemical assay. Consequently, IGHBP3 was selected as the candidate gene, which might be enriched in several metabolism-related pathways and cancer progression-related pathways. High expressions of IGHBP3 have an association with gender, advanced clinical stages, high T stages, and the presence of LNM. Survival analysis indicated that IGHBP3 may affect the prognosis of PTC patients. The use of a tissue chip confirmed the view that IGHBP3 might play a crucial role in the LNM of PTC. In conclusion, IGHBP3 might be involved in the development of LNM in PTC patients. IGHBP3 over-expression might be a novel indicator and a potential target for PTC therapy.

Radiomic analysis for preoperative prediction of cervical lymph node metastasis in patients with papillary thyroid carcinoma

PurposeCervical lymph node (LN) metastasis of papillary thyroid carcinoma (PTC) is critical for treatment and prognosis. We explored the feasibility of using radiomics to preoperatively predict cervical LN metastasis in PTC patients. MethodTotal 221 PTC patients (training cohort: n = 154; validation cohort: n = 67; divided randomly at the ratio of 7:3) were enrolled and divided into 2 groups based on LN pathologic diagnosis (N0: n = 118; N1a and N1b: n = 88 and 15, respectively). We extracted 546 radiomic features from non-contrast and venous contrast-enhanced computed tomography (CT) images. We selected 8 groups of candidate feature sets by minimum redundancy maximum relevance (mRMR), and obtained 8 radiomic sub-signatures by support vector machine (SVM) to construct the radiomic signature. Incorporating the radiomic signature, CT-reported cervical LN status and clinical risk factors, a nomogram was constructed using multivariable logistic regression. The nomogram's calibration, discrimination, and clinical utility were assessed. ResultsThe radiomic signature was associated significantly with cervical LN status (p < 0.01 for both training and validation cohorts). The radiomic signature showed better predictive performance than any radiomic sub-signatures devised by SVM. Addition of radiomic signature to the nomogram improved the predictive value (area under the curve (AUC), 0.807 to 0.867) in the training cohort; this was confirmed in an independent validation cohort (AUC, 0.795 to 0.822). Good agreement was observed using calibration curves in both cohorts. Decision curve analysis demonstrated the radiomic nomogram was worthy of clinical application. ConclusionsOur radiomic nomogram improved the preoperative prediction of cervical LN metastasis in PTC patients.

Efficacy of Shear-Wave Elastography for Detecting Postoperative Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma.

Aims To evaluate shear-wave elastography (SWE) as a tool to detect postoperative cervical lymph node (LN) metastasis in patients with papillary thyroid carcinoma (PTC). Methods Forty-three LNs of 43 patients with PTC undergoing ultrasound (US) and SWE before ultrasound-guided fine-needle aspiration (FNA) for the evaluation of postoperative cervical LN recurrences were analyzed. The mean (EMean), minimum (EMin), maximum (EMax), and standard deviation (ESD) of SWE elasticity indices were measured. Results Among 43 indeterminate or suspicious LNs, 12 were malignant and 31 were benign. The EMean, EMin, EMax, and ESD values were significantly higher in malignant LNs than in benign LNs (EMean: 37.1 kPa in malignant versus 11.8 kPa in benign LNs, P < 0.001; EMin: 11.3 kPa versus 5.1 kPa, P = 0.046; EMax: 50.5 kPa versus 23.7 kPa, P < 0.001; and ESD: 7.8 kPa versus 4.1 kPa, P = 0.006). EMax had the highest accuracy (93.0%) when applied with a cut-off value of 37.5 kPa. It had a positive likelihood ratio of 25.83 and a diagnostic odds ratio of 150.0. Conclusions The shear elasticity index of EMax, with higher likelihood ratios for malignant LNs, may help identify postoperative cervical LN metastasis in PTC patients with indeterminate or suspicious LNs.

RETRACTED ARTICLE: Relationship between VEGF protein expression and lymph node metastasis in papillary thyroid carcinoma among Asians: a meta-analysis

We carried out the current meta-analysis of relevant cohort studies in an attempt to investigate the relationships between vascular endothelial growth factor (VEGF) protein expression and lymph node (LN) metastasis in papillary thyroid carcinoma (PTC) among Asians. A range of electronic databases were searched, including Web of Science (1945∼2013), the Cochrane Library Database (Issue 12, 2013), MEDLINE (1966∼2013), EMBASE (1980∼2013), CINAHL (1982∼2013), and Chinese Biomedical Database (CBM) (1982~2013) with cross-referencing without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratio (OR) with their 95 % confidence interval (95 %CI) was calculated. Twelve clinical cohort studies with a total of 1,045 PTC patients were included in our meta-analysis, The results of our meta-analysis revealed that patients with VEGF-positive tumors had a 3.02-fold higher risk of LN metastasis than that of patients with VEGF-negative tumors (OR=3.02, 95 %CI=2.05~4.43, P<0.001). Furthermore, subgroup analysis by country suggested that VEGF-positive expression was associated with an increased risk of LN metastasis in PTC patients among Chinese populations (OR=3.33, 95 %CI=2.30~4.83, P<0.001), but not among Korean, Turkish, and Japanese populations (all P>0.05). Our findings support the view that VEGF protein expression may be correlated with LN metastasis in PTC patients, especially among Chinese populations.

Expression of TGF-β1, SNAI1 and MMP-9 is associated with lymph node metastasis in papillary thyroid carcinoma

TGF-β1, SNAI1 and MMP-9 are implicated in tumor invasion and metastasis. The purpose of this study was to examine TGF-β1, SNAI1 and MMP-9 expression in papillary thyroid carcinoma (PTC), and to assess association of TGF-β1, SNAI1 and MMP-9 expression with several clinicopathological indicators of PTC. TGF-β1, SNAI1 and MMP-9 protein expression in 83 PTCs and their matched normal thyroid specimens were analyzed using immunohistochemistry. The mRNA expression levels of TGF-β1, SNAI1 and MMP-9 in 12 fresh PTC specimens with lymph node metastasis (LNM), 12 fresh PTC specimens without LNM and their matched normal thyroid specimens were assessed by real-time RT-PCR. The results showed that the mRNA and protein expression levels of TGF-β1, SNAI1 and MMP-9 were significantly higher in PTCs than in their matched normal thyroid tissues. There were not significant differences in TGF-β1, SNAI1 and MMP-9 protein expression relative to age, gender, tumor size and TNM stage, except for MMP-9 whose protein expression correlated with tumor size. However, high mRNA and protein expression levels of TGF-β1, SNAI1 and MMP-9 were significantly correlated with LNM. Furthermore, TGF-β1, SNAI1 and MMP-9 protein expression were significantly correlated with one another. Concomitant expression of any two or all of the three molecules had stronger correlation with LNM than did each alone. Collectively, the present results indicate that immunohistochemical and real-time RT-PCR evaluation of TGF-β1, SNAI1 and MMP-9 expression in PTC may be useful to predict the risk of LNM in PTC patients.