High Expression of Interleukin-12A and Its Association with the Clinicopathology and Prognosis of Differentiated Thyroid Cancer

Background: The inflammatory microenvironment is closely related to the occurrence and development of cancer. Members of the interleukin-12 (IL-12) cytokine family play synergistic or antagonistic roles in the tumor microenvironment, in the form of classic heterodimers or newly discovered monomers or homodimers. Objective: The purpose of this study was to investigate the association between IL-12A and the clinicopathology and prognosis of differentiated thyroid cancer (DTC). Methods: A total of 101 pathologically confirmed DTC patients were included in this study. Immunohistochemistry was performed to assess IL-12A expression in DTC and corresponding paracancerous tissues. The associations of IL-12A with clinicopathology and prognosis were evaluated. Results: IL-12A was expressed in both normal thyroid tissues and DTC, but its expression level was significantly higher in DTC than in normal thyroid tissues (p < 0.001). IL-12A was positively correlated with tumor size (p = 0.027), risk stratification (p = 0.020), and TNM (Tumor-Node-Metastasis) stage (p = 0.024), but not with age, sex, pathological type, multifocality, extrathyroid extension, lymph node metastasis, and distant metastasis (all p > 0.05). Lymphocytic thyroiditis was found in 26/101 patients (25.7%), which was negatively associated with IL-12A expression (p = 0.018). Multivariate logistic regression analysis showed that risk stratification was the significant independent predictor of IL-12A expression. The rate of disease persistence or recurrence (P&R) was 13/101 (12.9%), and a positive relationship was found between IL-12A expression and P&R (p = 0.020). Disease-free survival was affected by factors such as tumor size, extrathyroid extension, tumor stage (T stage), and IL-12A expression, with p values of 0.006, 0.048, 0.002, and 0.012, respectively. Multivariate Cox proportional-hazards analysis showed that tumor size ≥2 cm (hazard ratio [HR] = 4.041 [95% CI: 1.144–14.274], p = 0.031) and high IL-12A expression (HR = 4.027 [95% CI 1.014–15.994], p = 0.049) were independent predictors of prognosis of DTC patients. Conclusions: IL-12A is highly expressed in DTC and is associated with disease aggressiveness. In addition, IL-12A is an independent predictor of the outcome of DTC.

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The Implication of Lymph Node Metastasis on Survival in Patients with Well-Differentiated Thyroid Cancer

The American Surgeon ◽

10.1177/000313480507100907 ◽

2005 ◽

Vol 71 (9) ◽

pp. 731-734 ◽

Cited By ~ 129

Author(s):

Yale D. Podnos ◽

David Smith ◽

Lawrence D. Wagman ◽

Joshua D.I. Ellenhorn

Keyword(s):

Thyroid Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Tumor Size ◽

Large Scale ◽

Differentiated Thyroid Cancer ◽

Lymph Node Status ◽

Large Tumor ◽

Node Metastasis ◽

Well Differentiated

Though survival for well-differentiated thyroid cancer is very good, specific populations suffer greater recurrence and mortality. Defining these cohorts can significantly influence prognosis and extent of treatment. This study, using a large, multi-institutional database, seeks to determine how the presence of lymph node disease in patients with well-differentiated thyroid cancer affects outcome. The Surveillance, Epidemiology, and End Results (SEER) database is a large-scale sample of 14 per cent of the U.S. population. It was used to identify patients with papillary and follicular thyroid carcinomas and identify the prognostic implications of lymph node metastasis. Additional factors, including presence of metastasis, age, and tumor size, were compared using multivariate and χ2 analyses. Of 19,918 patients identified, lymph node status was known for 9,904 (49.7%). On multivariate analysis, age >45 years, presence of distant metastasis, large tumor size, and lymph node involvement significantly predicted poor outcome. Overall survival at 14 years was 82 per cent for node negative and 79 per cent for node positive patients ( P < 0.05). This study shows that the survival of patients with well-differentiated thyroid cancer is adversely affected by lymph node metastases. The optimum treatment for this cohort needs further delineation, as particular populations are at greater risk of recurrence and death.

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TUMOR SIZE IS AN INDEPENDENT PREDICTOR OF MORTALITY RISK IN DIFFERENTIATED THYROID CANCER PATIENTS WITH T4 DISEASE

Endocrine Practice ◽

10.4158/ep-2019-0385 ◽

2020 ◽

Vol 26 (5) ◽

pp. 499-507

Author(s):

Zhengshi Wang ◽

Qian Zhang ◽

Hongmei Ye ◽

Chengyou Jia ◽

Zhongwei Lv ◽

...

Keyword(s):

Thyroid Cancer ◽

Tumor Size ◽

Differentiated Thyroid Cancer ◽

Multivariate Analyses ◽

Staging System ◽

Stage Iii ◽

Disease Specific Survival ◽

Tumor Node Metastasis ◽

Node Metastasis ◽

Disease Specific

Objective: The eighth edition of the American Joint Committee on Cancer (AJCC) guideline on the tumor-node-metastasis staging system has been applied in clinical practice for thyroid cancer since 2018. However, using these criteria, a few studies have shown no significant difference between stage III and IV diseases amongst the differentiated thyroid cancer (DTC) patients. Thus, we aimed to study the underlying reason behind this observation. Methods: Patients were selected from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. The Cox proportional hazards regression model was used for the univariate and multivariate analyses to plot the Kaplan-Meier survival curves for overall survival (OS) and disease-specific survival (DSS). Results: A total of 1,431 patients had a median tumor size of 3.0 cm (range: 0.1 to 50 cm). When stratified by tumor size (≤2 cm, 2 to 4 cm, and >4 cm), lower survival rates were observed in patients with stage III (T4a) cancer and large tumor size than in those with stage IVA (T4b) cancer and small tumor size. Univariate and multivariate analyses showed that tumor size (≤4 cm versus >4 cm) is an independent prognostic factor for OS ( P<.001) and DSS ( P<.001) in DTC patients with T4a and T4b diseases. Conclusion: Tumor size is an independent prognostic factor for OS and DSS in DTC patients with T4 disease; tumor size-related modification of the T4 category can improve the AJCC staging system for DTC patient with stage III–IV diseases. Abbreviations: AJCC = American Joint Committee on Cancer; CI = confidence interval; DSS = disease-specific survival; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; HR = hazard ratio; OS = overall survival; PTC = papillary thyroid cancer; SEER = Surveillance, Epidemiology, and End Results; TNM = tumor-node-metastasis

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Synergic effects of histology subtype, tumor size, and lymph node metastasis on distant metastasis in differentiated thyroid cancer

Annals of Translational Medicine ◽

10.21037/atm.2019.09.137 ◽

2019 ◽

Vol 7 (20) ◽

pp. 533-533 ◽

Cited By ~ 2

Author(s):

Zeming Liu ◽

Sichao Chen ◽

Yihui Huang ◽

Di Hu ◽

Wen Zeng ◽

...

Keyword(s):

Thyroid Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Distant Metastasis ◽

Tumor Size ◽

Differentiated Thyroid Cancer ◽

Node Metastasis

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Validation of dynamic risk stratification in pediatric differentiated thyroid cancer

Endocrine ◽

10.1007/s12020-017-1381-7 ◽

2017 ◽

Vol 58 (1) ◽

pp. 167-175 ◽

Cited By ~ 7

Author(s):

Seo Young Sohn ◽

Young Nam Kim ◽

Hye In Kim ◽

Tae Hyuk Kim ◽

Sun Wook Kim ◽

...

Keyword(s):

Thyroid Cancer ◽

Risk Stratification ◽

Differentiated Thyroid Cancer ◽

Dynamic Risk

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ASO Author Reflections: Preoperative Risk Stratification in Differentiated Thyroid Cancer

Annals of Surgical Oncology ◽

10.1245/s10434-018-7057-6 ◽

2018 ◽

Vol 25 (S3) ◽

pp. 878-879

Author(s):

Kyle Zanocco

Keyword(s):

Thyroid Cancer ◽

Risk Stratification ◽

Differentiated Thyroid Cancer ◽

Preoperative Risk ◽

Preoperative Risk Stratification

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Reconsideration of tumor size threshold for total thyroidectomy in differentiated thyroid cancer

Surgery ◽

10.1016/j.surg.2018.04.019 ◽

2018 ◽

Vol 164 (3) ◽

pp. 504-510 ◽

Cited By ~ 14

Author(s):

Shih-Ping Cheng ◽

Ming-Nan Chien ◽

Tao-Yeuan Wang ◽

Jie-Jen Lee ◽

Chun-Chuan Lee ◽

...

Keyword(s):

Thyroid Cancer ◽

Total Thyroidectomy ◽

Tumor Size ◽

Differentiated Thyroid Cancer ◽

Size Threshold

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The Influence of Age on Disease Outcome in 2015 ATA High Risk Differentiated Thyroid Cancer Patients

Acta Endocrinologica ◽

10.1530/eje-21-0365 ◽

2021 ◽

Author(s):

Evert F.s. van Velsen ◽

Robin P. Peeters ◽

Merel T. Stegenga ◽

F.j. van Kemenade ◽

Tessa M. van Ginhoven ◽

...

Keyword(s):

Thyroid Cancer ◽

High Risk ◽

Risk Stratification ◽

Differentiated Thyroid Cancer ◽

Response To Therapy ◽

Disease Outcome ◽

High Risk Patients ◽

Risk Patients ◽

Stratification System ◽

Risk Stratification System

Objective Recent research suggests that the addition of age improves the 2015 American Thyroid Association (ATA) Risk Stratification System for differentiated thyroid cancer (DTC). The aim of our study was to investigate the influence of age on disease outcome in ATA High Risk patients with a focus on differences between patients with papillary (PTC) and follicular thyroid cancer (FTC). Methods We retrospectively studied adult patients with High Risk DTC from a Dutch university hospital. Logistic regression and Cox proportional hazards models were used to estimate the effects of age (at diagnosis) and several age cutoffs (per five years increment between 20 and 80 years) on (i) response to therapy, (ii) developing no evidence of disease (NED), (iii) recurrence, and (iv) disease specific mortality (DSM). Results We included 236 ATA High Risk patients (32% FTC) with a median follow-up of 6 years. Age, either continuously or dichotomously, had a significant influence on having an excellent response after initial therapy, developing NED, recurrence, and DSM for PTC and FTC. For FTC, an age cutoff of 65 or 70 years showed the best statistical model performance, while this was 50 or 60 years for PTC. Conclusions In a population of patients with High Risk DTC, older age has a significant negative influence on disease outcomes. Slightly different optimal age cutoffs were identified for the different outcomes, and these cutoffs differed between PTC and FTC. Therefore, the ATA Risk Stratification System may further improve should age be incorporated as an additional risk factor.

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