Abstract 2425: Prevalence of NTRK fusions and clinico-pathological characteristics of Middle Eastern papillary thyroid cancer revealed enrichment in BRAF wild-type PTC

2021 ◽  
Author(s):  
Abdul K. Siraj ◽  
Rong Bu ◽  
Sandeep K. Parvathareddy ◽  
Yan Kong ◽  
Padmanaban Annaiyappanaidu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Middle Eastern ◽  
Papillary Thyroid ◽  
Wild Type ◽  
Pathological Characteristics

Abstract 730: Annual hazard rate of recurrence in Middle-Eastern papillary thyroid cancer over a long-term follow-up

2021 ◽  
Author(s):  
Abdul K. Siraj ◽  
Sandeep K. Parvathareddy ◽  
Zeeshan Qadri ◽  
Saud Azam ◽  
Felisa De Vera ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Hazard Rate ◽  
Middle Eastern ◽  
Papillary Thyroid ◽  
Long Term Follow Up

scholarly journals Annual Hazard Rate of Recurrence in Middle Eastern Papillary Thyroid Cancer over a Long-Term Follow-Up

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3624
Author(s):  
Abdul K. Siraj ◽  
Sandeep Kumar Parvathareddy ◽  
Zeeshan Qadri ◽  
Khawar Siddiqui ◽  
Saif S. Al-Sobhi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Hazard Rate ◽  
Tumor Recurrence ◽  
Cox Regression ◽  
Middle Eastern ◽  
Treatment Strategies ◽  
Recurrence Risk ◽  
Papillary Thyroid ◽  
Cox Regression Analysis

Predicting the pattern of recurrence in papillary thyroid cancer (PTC) is necessary to establish optimal surveillance and treatment strategies. We analyzed changes in hazard rate (HR) for tumor recurrence over time in 1201 unselected Middle Eastern PTC patients. The changes in risk were further analyzed according to clinical variables predictive of early (≤5 years) and late (>5 years) recurrence using Cox regression analysis to identify patient populations that remain at risk. Tumor recurrence was noted in 18.4% (221/1201) patients. The annualized hazard of PTC recurrence was highest during the first 5 years (2.8%), peaking between 1 and 2 years (3.7%), with a second smaller peak between 13 and 14 years (3.2%). Patients receiving radioactive iodine (RAI) therapy had lower recurrence hazard compared to those who did not (1.5% vs. 2.7%, p = 0.0001). Importantly, this difference was significant even in intermediate-risk PTC patients (0.7% vs. 2.3%; p = 0.0001). Interestingly, patients aged ≥55 years and having lymph node metastasis were at persistent risk for late recurrence. In conclusion, we confirmed the validity of the double-peaked time-varying pattern for recurrence risk in Middle Eastern PTC patients and our findings could help in formulating individualized treatment and surveillance plans.

scholarly journals Therapeutic Potential of Dickkopf-1 in Wild-Type BRAF Papillary Thyroid Cancer via Regulation of β-Catenin/E-cadherin Signaling

2014 ◽  
Vol 99 (9) ◽  
pp. E1641-E1649 ◽  
Author(s):  
Sun Wook Cho ◽  
Young A. Kim ◽  
Hyun Jin Sun ◽  
Hwa Young Ahn ◽  
Eun Kyung Lee ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Therapeutic Potential ◽  
Papillary Thyroid ◽  
Wild Type ◽  
Dickkopf 1 ◽  
E Cadherin

scholarly journals POLE and POLD1 pathogenic variants in the proofreading domain in papillary thyroid cancer

2020 ◽  
Vol 9 (9) ◽  
pp. 923-932
Author(s):  
Abdul K Siraj ◽  
Rong Bu ◽  
Maham Arshad ◽  
Kaleem Iqbal ◽  
Sandeep Kumar Parvathareddy ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Middle Eastern ◽  
Stage Iv ◽  
Pathogenic Variant ◽  
Eastern Region ◽  
Papillary Thyroid ◽  
Pathogenic Variants ◽  
Middle Eastern Population ◽  
Low Expression

Thyroid cancer is the most frequent endocrine cancer with an increasing incidence rate worldwide and is the second most common malignancy among females in Saudi Arabia. Papillary thyroid cancer (PTC) is the most common subtype. Germline pathogenic variants in the proofreading domain of the POLE and POLD1 genes predispose to several types of cancers. However, the role of pathogenic variants of these two genes in PTC remains unknown. Capture sequencing, Sanger sequencing and immunohistochemistry were performed on 300 PTC cases from the Middle Eastern region. One germline pathogenic variant each of POLE (1/300, 0.33%) and POLD1 (1/300, 0.33%) genes was identified. Low expression of POLD1 was detected in 46.5% (133/286) of cases and was significantly associated with the follicular variant of PTC (P = 0.0006), distant metastasis (P = 0.0033) and stage IV tumours (P = 0.0081). However, no somatic pathogenic variant was detected in POLE gene. Furthermore, low expression of POLE was noted in 61.7% (175/284) of cases with no significant clinicopathological associations. Our study shows that pathogenic variant in the POLE and POLD1 proofreading domain is a cause of PTC and low expression of POLD1 is associated with poor prognostic markers in the Middle Eastern population. Further studies from different geographic populations are needed to determine the frequency and spectrum of proofreading domain pathogenic variants in POLE and POLD1 genes and in PTC from different ethnicities.

BRAF V600E and Retinoic Acid in Radioiodine-Refractory Papillary Thyroid Cancer

2018 ◽  
Vol 51 (01) ◽  
pp. 69-75 ◽  
Author(s):  
Jan Groener ◽  
Debora Gelen ◽  
Carolin Mogler ◽  
Esther Herpel ◽  
Csaba Toth ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Retinoic Acid ◽  
Papillary Thyroid Cancer ◽  
Initial Response ◽  
University Hospital ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Wild Type ◽  
Mutational Status ◽  
Before And After

AbstractRadioiodine refractoriness in differentiated thyroid cancer remains an unsolved therapeutic problem. Response to retinoids might depend on specific genetic markers. In this retrospective analysis, associations between BRAF V600E and clinical outcomes after redifferentiation with retinoic acid (RA) and radioiodine therapy (RIT) were investigated. Thirteen patients with radioiodine-refractory (RAI-R) papillary thyroid cancer (PTC) were treated with 13-cis-RA followed by iodine-131 treatment at the Department of Endocrinology, Heidelberg University Hospital, Heidelberg, Germany. DNA sequencing was performed in formalin-fixed paraffin-embedded tissue. Clinical outcome parameters were tumor size, thyroglobulin, and radioiodine uptake in correlation to mutational status. Differences of each parameter were compared before and after RA/RIT. Initial response showed no difference in patients with BRAF V600E compared to patients with wild type. However, after a median follow-up of 2 and a half years, 2 out of 3 patients with BRAF V600E showed response compared to 5 out of 9 with wild type under consideration of all 3 parameters. In this small cohort, more RAI-R PTC patients with BRAF V600E receiving redifferentiation therapy showed response. Verification in a larger study population analyzing mutational status in patients with RAI-R PTC might be helpful to identify patients where redifferentiation therapy might lead to an improved outcome.

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