Abstract LBA042: Male Sex is an Independent Predictor of Recurrence-Free Survival in Middle Eastern Papillary Thyroid Carcinoma

Author(s):  
KHAWLA S. AL-KURAYA ◽  
Sandeep Kumar Parvathareddy ◽  
Abdul K Siraj ◽  
Felisa De Vera ◽  
Padmanaban Annaiyappanaidu ◽  
...  
2014 ◽  
Vol 21 (2) ◽  
pp. 285-295 ◽  
Author(s):  
Brian Hung-Hin Lang ◽  
Young Jun Chai ◽  
Benjamin J Cowling ◽  
Hye Sook Min ◽  
Kyu Eun Lee ◽  
...  

Utilizing BRAFV600E mutation as a marker may reduce unnecessary prophylactic central neck dissection (pCND) in clinically nodal negative (cN0) neck for small (≤2 cm) classical papillary thyroid carcinoma (PTC). We aimed to assess whether BRAF is a significant independent predictor of occult central nodal metastasis (CNM) and its contribution to the overall prediction after adjusting for other significant preoperative clinical factors in small PTC. Primary tumor tissue (paraffin-embedded) from 845 patients with small classical cN0 PTC who underwent pCND was tested for BRAF mutation. Clinicopathologic factors were compared between those with and without BRAF. BRAF was evaluated to see if it was an independent factor for CNM. Prediction scores were generated using logistic regression models and their predictability was measured by the area under the ROC curve (AUC). The prevalence of BRAF was 628/845 (74.3%) while the rate of CNM was 285/845 (33.7%). Male sex (odds ratio (OR): 2.68, 95% CI: 1.71–4.20), large tumor size (OR: 2.68, 95% CI: 1.80–4.00), multifocality (OR: 1.49, 95% CI: 1.07–2.09), lymphovascular permeation (OR: 10.40, 95% CI: 5.18–20.88), and BRAF (OR: 1.65, 95% CI: 1.10–2.46) were significant independent predictors of CNM, while coexisting Hashimoto's thyroiditis (OR: 0.56, 95% CI: 0.40–0.80) was an independent protective factor. The AUC for prediction score based on tumor size and male sex was similar to that of prediction score based on tumor size, male sex, and BRAF status (0.68 vs 0.69, P=0.60). Although BRAF was an independent predictor of CNM, knowing its status did not substantially improve the overall prediction. A simpler prediction score based on male sex and tumor size might be sufficient.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3042 ◽  
Author(s):  
Young Mun Jeong ◽  
Haejin Cho ◽  
Tae-Min Kim ◽  
Yourha Kim ◽  
Sora Jeon ◽  
...  

CD73 is involved in tumor immune escape and promotes the growth and progression of cancer cells. The functional role of CD73 expression in papillary thyroid carcinoma (PTC) has not yet been established. In 511 patients with PTC, immunohistochemistry for CD73 on tissue microarrays showed that the high expression of CD73 was associated with an aggressive histologic variant (p = 0.002), extrathyroidal extension (p < 0.001), lymph node metastasis (p < 0.001), and BRAFV600E mutation (p = 0.015). Survival analysis results showed that patients with high CD73 expression had worse recurrence-free survival (p = 0.023). CD73 inhibitors induced G1 cell cycle arrest and apoptosis, inhibited the migration and invasion of PTC cells, and suppressed tumor growth in PTC xenograft nude mice. High expression of CD73 (NT5E) mRNA was associated with unfavorable clinicopathologic characteristics, the abundance of Tregs and dendritic cells, depletion of natural killer (NK) cells, and high expression of immune checkpoint genes and epithelial-to-mesenchymal transition-related genes in The Cancer Genome Atlas (TCGA) dataset. Taken together, CD73 expression promotes tumor progression and predicts low recurrence-free survival. Targeting the CD73–adenosine axis in the tumor microenvironment offers an attractive pathway for therapeutic strategies aimed at advanced PTC.


2021 ◽  
Vol 22 (15) ◽  
pp. 7833
Author(s):  
Abdul K. Siraj ◽  
Pratheesh Kumar Poyil ◽  
Sandeep Kumar Parvathareddy ◽  
Khadija Alobaisi ◽  
Saeeda O. Ahmed ◽  
...  

Thyroid cancer incidence has increased in recent decades. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Approximately 30% of PTC patients develop recurrence or distant metastasis and tend to have poor prognosis. Therefore, the identification of targetable biomarkers in this subset of patients is of great importance. Accumulating evidence indicates that zinc finger protein 677 (ZNF677), which belongs to the zinc finger protein family, is an important effector during the progression of multiple malignancies. However, its role in Middle Eastern PTC patients has not been fully illustrated. Here, we uncovered the molecular mechanism and the clinical impact of ZNF677 expression in a large cohort of more than 1200 Middle Eastern PTC and 15 metastatic tissues. We demonstrated that ZNF677 is frequently downregulated in primary PTC (13.6%, 168/1235) and showed that complete loss of expression of ZNF677 is significantly associated with aggressive clinico-pathological markers such as extrathyroidal extension (p = 0.0008) and distant metastases (p < 0.0001). We also found a significantly higher incidence of ZNF677 loss in primary tumors with distant metastases (33.3%; p < 0.0001) as well as in distant metastatic tissues (46.7%; p = 0.0002) compared to the overall cohort (13.6%). More importantly, PTC with loss of ZNF677 expression showed significantly lower metastasis-free survival (p = 0.0090). Interestingly, on multivariate logistic regression analysis, ZNF677 loss was an independent predictor of distant metastasis in PTC (Odds ratio = 2.60, 95% Confidence interval = 1.20–5.62, p = 0.0155). In addition, we found a significant association between ZNF677 loss and phospho-AKT expression (p < 0.0001). Our functional molecular results suggest that ZNF677 acts as a tumor suppressor, mediating its effect by inhibiting AKT phosphorylation. Taken together, our results highlight the pivotal role played by ZNF677 during carcinogenesis and metastasis formation in Middle Eastern PTC patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mengli Guo ◽  
Zhen Chen ◽  
Yayi Li ◽  
Sijin Li ◽  
Fei Shen ◽  
...  

BackgroundThe risk factors of papillary thyroid carcinoma (PTC) recurrence are meaningful for patients and clinicians. Tumor mutation burden (TMB) has been a biomarker for the effectiveness of immune checkpoint inhibitor (ICI) and prognosis in cancer. However, the role of TMB and its latent significance with immune cell infiltration in PTC are still unclear. Herein, we aimed to explore the effect of TMB on PTC prognosis.Material and MethodsRNA-seq and DNA-seq datasets of PTC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The Gene Ontology (GO) and gene set enrichment analysis (GSEA 4.0.1) were applied further to explore potential differences in PTC patients’ biological functions. The differentially expressed genes (DEGs) and immune microenvironment between the high and low TMB groups were determined.ResultsTMB had the highest AUC score than other clinical indicators in ROC analysis on recurrence-free survival, and a higher TMB score was related to a worse prognosis. Further, GSEA showed a higher level of oxidative phosphorylation (OXPHOS) in the high TMB group, and four genes correlated with recurrence-free survival rate were identified. The abundance of CD8+ T cells and M1 macrophages in the high TMB group was significantly lower than that in the low TMB group.ConclusionsOur study found that TMB was a better predictor variable at evaluating the risk of PTC recurrence. Moreover, TMB-related genes conferred dramatically correlated prognosis, which was worth exploring in guiding postoperative follow-up and predicting recurrence for PTC patients.


2021 ◽  
Vol 25 (4) ◽  
pp. 351-360
Author(s):  
Bahareh SHATERI AMIRI ◽  
Mahboobeh HEMMATABADI ◽  
Soghra RABIZADEH ◽  
Hamideh HASANNEJAD ◽  
Alireza ESTEGHAMATI ◽  
...  

1999 ◽  
Vol 34 (12) ◽  
pp. 1799-1804 ◽  
Author(s):  
Catherine A Welch Dinauer ◽  
R.Michael Tuttle ◽  
Daniel K Robie ◽  
Donald R McClellan ◽  
Gary L Francis

2017 ◽  
Vol 132 (1) ◽  
pp. 8-13 ◽  
Author(s):  
J Mansour ◽  
D Sagiv ◽  
E Alon ◽  
Y Talmi

AbstractObjective:Cervical metastases in papillary thyroid carcinoma are associated with increased recurrence. However, their effect on survival remains controversial. This study evaluated literature on the prognostic value of lymph node ratio for loco-regional recurrence and survival in metastatic papillary thyroid carcinoma.Methods:The PubMed database was systematically searched using the terms ‘papillary thyroid carcinoma’ and ‘lymph node ratio’. Articles addressing the association between lymph node ratio and loco-regional recurrence or survival were identified.Results:Nine retrospective studies were included, comprising 12 400 post-thyroidectomy and neck dissection papillary thyroid carcinoma patients (median age, 48.6 years; 76 per cent females). Lymph node ratio was associated with worse recurrence-free survival in 60 and 75 per cent of studies investigating the effect of central compartment metastases and both central and lateral compartment metastases on recurrence-free survival, respectively. One large population-based study showed an association between lymph node ratio and disease-specific mortality in N1nodal disease, but failed to maintain the same association when N1bpatients were excluded.Conclusion:Regional lymph node ratio is an independent predictor for loco-regional recurrence in pathologically staged N1patients with papillary thyroid carcinoma. Patients with a high lymph node ratio should be closely followed up.


2021 ◽  
Vol 12 ◽  
Author(s):  
Tengfei Ma ◽  
Haiyang Wang ◽  
Jifeng Liu ◽  
Jian Zou ◽  
Shixi Liu

ObjectiveTo determine whether papillary thyroid carcinoma (PTC) patients with benign or nonsuspicious nodules in the contralateral lobe have a higher rate of recurrence or worse survival after lobectomy compared to those without nodules in the contralateral lobe.MethodsAdult patients who underwent lobectomy and were diagnosed with unilateral PTC (2013-2015), were identified from an institutional database. Patients who previously had cytologically benign nodules or nonsuspicious nodules in the contralateral lobe comprised the contralateral nodule (CN) group. Patients who did not have nodules in the contralateral lobe comprised the unilateral nodule (UN) group.Results370 patients were included: 242 in the UN group and 128 in the CN group. After a median follow-up of 62 months (range, 16–85 months), recurrence was confirmed in 4.1% patients in the UN group and 5.5% patients in the CN group (p = 0.559). Clinical contralateral lobe PTC was detected in 2.9% (7/242) of patients from the UN group and 3.9% (5/128) of patients from the CN group (p = 0.601). The 5-year contralateral lobe recurrence-free survival (RFS) rates were 96.8% in the UN group and 97.4% in the CN group (p = 0.396). The 5-year loco-regional RFS rates were 98.4% in the UN group and 97.8% in the CN group (p = 0.690). The 5-year disease-specific survival rates were both 100%.ConclusionPTC patients with benign or nonsuspicious CNs have similar recurrence and survival rates after lobectomy compared to those without CNs. CNs alone should not be an indication for total or completion thyroidectomy.


2015 ◽  
Vol 22 (4) ◽  
pp. 679-686 ◽  
Author(s):  
Seog Yun Park ◽  
Yuh-S Jung ◽  
Chang Hwan Ryu ◽  
Chang Yoon Lee ◽  
You Jin Lee ◽  
...  

We undertook this study to estimate an accurate incidence and spread patterns of occult papillary thyroid carcinoma (PTC) in patients with a preoperative diagnosis of solitary PTC by using whole-specimen mapping of all specimens after a total thyroidectomy. Enrolled prospectively in this whole-thyroid mapping study are 82 consecutive patients who underwent a total thyroidectomy under a preoperative diagnosis of solitary PTC. All thyroidectomy specimens were serially sectioned in 2 mm thickness and whole-thyroid mapping was carried out for additional foci of occult PTC. The frequencies of occult lesions detected in the whole and contralateral lobe were determined, and clinicopathologic factors associated with multifocality were assessed. Whole-thyroid mapping revealed 66 occult PTC lesions missed by preoperative ultrasound in 37 (45.1%) of the 82 patients. The great majority (92.5%) of the occult PTC was smaller than 3 mm in size and 25 patients (30.5%) had contralateral lesions. We found that the male sex was an independent predictor of multifocality (odds ratio (OR), 3.00; 95% CI, 1.11–8.14), adjusting for preoperative findings. Analysis with pathologic parameters showed that the male sex (OR, 5.03; 95% CI, 1.68–15.08) and extrathyroidal extensions (OR, 3.03; 95% CI, 1.03–8.95) were associated with multifocal PTC. However, none of the clinicopathologic factors evaluated predicted contralateral PTC. Our study demonstrates the diagnostic limitations of ultrasound for the detection of multifocal PTC and the need to consider the possibility of occult lesions in the management of solitary PTC, especially in male patients.


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