scholarly journals BRAF Mutation Predicts a Poorer Clinical Prognosis for Papillary Thyroid Cancer

2005 ◽  
Vol 90 (12) ◽  
pp. 6373-6379 ◽  
Author(s):  
Mingzhao Xing ◽  
William H. Westra ◽  
Ralph P. Tufano ◽  
Yoram Cohen ◽  
Eli Rosenbaum ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Thyroid Cancer ◽  
Risk Stratification ◽  
Papillary Thyroid Cancer ◽  
Braf Mutation ◽  
Advanced Tumor Stage ◽  
Papillary Thyroid ◽  
Clinical Prognosis ◽  
Mutation Status ◽  
Predictors Of Recurrence

Context: Use of BRAF mutation in papillary thyroid cancer (PTC) has the potential to improve risk stratification of this cancer. Objective: The objective of the study was to investigate the prognostic value of BRAF mutation in patients with PTC. Design, Setting, and Subjects: In a multicenter study of 219 PTC patients, data on their clinicopathological characteristics and clinical courses between 1990 and 2004 were retrospectively collected, and their tumor BRAF mutation status was determined. Associations of BRAF mutation with initial tumor characteristics and subsequent recurrence were analyzed. Main Outcome Measure: Relationships between the BRAF mutation status and clinicopathological outcomes, including recurrence, were measured. Results: We found a significant association between BRAF mutation and extrathyroidal invasion (P < 0.001), lymph node metastasis (P < 0.001), and advanced tumor stage III/IV (P = 0.007) at initial surgery. This association remained significant on multivariate analysis, adjusting for conventional clinicopathological predictors of recurrence excluding the histological PTC subtype, but was lost when the tumor subtype was included in the model. BRAF mutation was also significantly associated with tumor recurrence, 25 vs. 9% with and without mutation, respectively (P = 0.004), during a median of 15 (interquartile range, 3–29) months of follow-up. This association remained significant on multivariate analysis adjusting for conventional clinicopathological predictors of recurrence, even including the PTC subtype (odds ratio, 4.0; 95% confidence interval, 1.1–14.1; P = 0.03). BRAF mutation was even an independent predictor of recurrence in patients with stage I/II disease, 22 vs. 5% with and without BRAF mutation, respectively (P = 0.002). BRAF mutation was also more frequently associated with absence of tumor I-131 avidity and treatment failure of recurrent disease. Conclusions: In patients with PTC, BRAF mutation is associated with poorer clinicopathological outcomes and independently predicts recurrence. Therefore, BRAF mutation may be a useful molecular marker to assist in risk stratification for patients with PTC.

scholarly journals BRAF V600E Mutation-Assisted Risk Stratification of Solitary Intrathyroidal Papillary Thyroid Cancer for Precision Treatment

2017 ◽  
Vol 110 (4) ◽  
pp. 362-370 ◽  
Author(s):  
Yueye Huang ◽  
Shen Qu ◽  
Guangwu Zhu ◽  
Fei Wang ◽  
Rengyun Liu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Risk Stratification ◽  
Papillary Thyroid Cancer ◽  
Braf Mutation ◽  
Hazard Ratio ◽  
Braf V600e ◽  
Independent Effect ◽  
Papillary Thyroid ◽  
Wild Type ◽  
Recurrence Rates

Abstract Background Precise risk stratification-based treatment of solitary intrathyroidal papillary thyroid cancer (SI-PTC) that is larger than 1.0 cm and 4.0 cm or less is undefined. Methods A genetic-clinical risk study was performed on BRAF V600E in 955 patients (768 women and 187 men) with SI-PTC, with median age of 46 years and median clinical follow–up time of 64 months at 11 medical centers in six countries. The chi-square test or, for analyses with small numbers, Fisher’s exact test was performed to compare recurrence rates. Recurrence-free probability was estimated by Kaplan-Meier (KM) analysis, and the independent effect of BRAF mutation on the recurrence was analyzed by Cox regression and Cox proportional hazard analyses. All statistical tests were two-sided. Results Recurrence of SI-PTC larger than 1.0 cm and 4.0 cm or less was 9.5% (21/221) vs 3.4% (11/319) in BRAF mutation vs wild-type BRAF patients, with a hazard ratio (HR) of 3.03 (95% confidence interval [CI] = 1.46 to 6.30) and a patient age- and sex-adjusted hazard ratio of 3.10 (95% CI = 1.49 to 6.45, P = .002). Recurrence rates of SI-PTC larger than 2.0 cm and 4.0 cm or less were 16.5% (13/79) vs 3.6% (5/139) in mutation vs wild-type patients (HR = 5.44, 95% CI = 1.93 to 15.34; and adjusted HR = 5.58, 95% CI = 1.96 to 15.85, P = .001). Recurrence rates of SI-PTC larger than 3.0 cm and 4 cm or less were 30.0% (6/20) vs 1.9% (1/54) in mutation vs wild-type patients (HR = 18.40, 95% CI = 2.21 to 152.98; and adjusted HR = 14.73, 95% CI = 1.74 to 124.80, P = .01). Recurrences of mutation-positive SI-PTC were comparable with those of counterpart invasive solitary PTC, around 20% to 30%, in tumors larger than 2.0 cm to 3.0 cm. BRAF mutation was associated with a statistically significant decrease in recurrence-free patient survival on KM analysis, particularly in SI-PTC larger than 2.0 cm and 4.0 cm or less. Similar results were obtained in conventional SI-PTC. The negative predictive values of BRAF mutation for recurrence were 97.8% (95% CI = 96.3% to 98.8%) for general SI-PTC and 98.2% (95% CI = 96.3% to 99.3%) for conventional SI-PTC. Conclusions BRAF V600E identifies a subgroup of SI-PTC larger than 1.0 cm and 4.0 cm or less, particularly tumors larger than 2.0 cm and 4.0 cm or less, that has high risk for recurrence comparable with that of invasive solitary PTC, making more aggressive treatment reasonable.

scholarly journals PD-L1 Expression in Papillary Thyroid Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A867-A868
Author(s):  
Tripti Joshi ◽  
Ruta Gupta ◽  
Luisa Fernanda Olaya A ◽  
Bing Yu ◽  
Ash Gargya ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Risk Stratification ◽  
Treatment Response ◽  
Papillary Thyroid Cancer ◽  
Recurrence Risk ◽  
Staining Intensity ◽  
Papillary Thyroid ◽  
Clinicopathologic Characteristics ◽  
Mutation Status ◽  
Histological Variants

Abstract There is limited data on prevalence of PD-L1 expression in papillary thyroid cancer (PTC). Anti- PD-L1 therapy is now being trialled for head and neck cancers including thyroid cancer. Whether presence of PD-L1 staining in PTC might result in a better response to anti-PD-L1 therapy is uncertain. We evaluated the frequency of tumoral PD-L1 expression using standard antibody (SP263) and clinicopathologic factors including mutation status - BRAF, NRAS, KRAS using OncoFocus Mass Array System in an Australian PTC cohort with low or high risk of recurrence /treatment response as per 2015 ATA guidelines. The cohort had 128 patients; 66% were females; 40% had both multifocal and bilateral PTC; 47% had low recurrence risk, of whom 92% had excellent treatment response; 34% had high recurrence risk, of whom 37% had structural incomplete treatment response. There was nil (0%) PD-L1 staining in 59%, 1% staining in 20%, 5-10% staining in 11%, >10% staining in rest of the cohort; 30%, 40% and 70% staining was seen in 2% each. PD-L1 in immune cells was positive in 62%. There was no significant association between PD-L1 tumour status and age, gender, size of tumour, multifocality, bilaterality, both multifocality and bilaterality, lymphovascular invasion, perineural invasion, extrathyroidal extension (ETE), histological variants, risk stratification, treatment response, metastases or mutation status. Among PD-L1 negative vs positive patients, BRAFV600E was present in 64.9% vs 67.5%, NRAS in 8.8% vs 0% and nil mutation in 26 % vs 33 % p=0.15. The staining thresholds were chosen according to existing literature. When analysed according to the percentage of PD-L1 staining (0%, 1-10% and >=10% thresholds), there was no significant association between PD-L1 staining category and other features, except for ETE (35% vs 65% vs 27%; p=0.007), a relationship that remained significant in a multivariable-adjusted model (OR 9.9, p=0.04). PD-L1 staining thresholds of <5% and >=5% were significantly associated with the size of tumour (24.7±15.4 vs 33.3±21.8; p=0.02) and histological variants (57 % vs 61% for classic variants and 27% vs 11% for follicular variants, p=0.03). This is the first study to our knowledge that analysed PD-L1 staining based on the risk stratification categories. The majority of PTC showed negative or low staining intensity for PD-L1 expression. There was no significant association between PD-L1 staining, clinicopathologic characteristics and mutation status of the PTC. Relatively less ETE was seen in the group that showed >=10% and also >=5% PD-L1 staining as compared to the group that showed 1% <10% and 1% to <5% staining which is an interesting observation and needs further investigation. The significant variation in reported PD-L1 staining in current literature reiterates that the method is yet to be optimised. Moreover the relationship between PD-L1 staining and PTC remains to be further investigated.

scholarly journals The Risk of Relapse in Papillary Thyroid Cancer (PTC) in the Context of BRAFV600E Mutation Status and Other Prognostic Factors

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0132821 ◽  
Author(s):  
Agnieszka Czarniecka ◽  
Monika Kowal ◽  
Dagmara Rusinek ◽  
Jolanta Krajewska ◽  
Michal Jarzab ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Prognostic Factors ◽  
Papillary Thyroid Cancer ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Mutation Status ◽  
Risk Of Relapse

scholarly journals The Age Threshold of the 8th Edition AJCC Classification Is Useful for Indicating Patients with Aggressive Papillary Thyroid Cancer in Clinical Practice. 

2020 ◽  
Author(s):  
Krzysztof Kaliszewski ◽  
Dorota Diakowska ◽  
Łukasz Nowak ◽  
Beata Wojtczak ◽  
Jerzy Rudnicki
Keyword(s):  
Thyroid Cancer ◽  
Clinical Practice ◽  
Risk Stratification ◽  
Papillary Thyroid Cancer ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Papillary Thyroid ◽  
Locally Advanced Disease ◽  
In Series ◽  
8Th Edition

Abstract Background: Papillary thyroid cancer (PTC) is unique among cancers in that patient age is a consideration in staging. One of the most important modifications in the 8th Edition of the American Joint Committee on Cancer (AJCC) classification is to increase the age cut off for risk stratification in PTC from 45 to 55 years. However, whether this cut off is useful in clinical practice remains controversial. In the present study, we assessed how well this new age threshold stratifies patients with aggressive PTC.Methods: We retrospectively analyzed the clinicopathological features and overall survival rate of patients with PTC admitted to and surgically treated at a single surgical center. The study protocol was divided into two series. In each series all patients (n=523) were divided in 2 groups according to age cut off. In the first series (cut off 45) patients <45 (n=193) vs. ≥45 (n=330) were compared, and in the second series (cut off 55) patients <55 (n=306) vs. ≥55 (n=217) were compared.Results: The rate of the prevalence of locally advanced disease (pT3 and pT4) was significantly higher in the patients above 55 years old than in those below 55 years old (p=0.013). No significant differences were found for this parameter in series with cut off point 45 years old. A significantly higher risk of locally advanced disease T3+T4 (OR=4.87) and presence of LNM (N1) (OR=3.78) was observed in ≥45 years old group (p=0.021 and p<0.0001, respectively). More expressive results were found for the patients ≥55 years old group, where the risk of locally advanced disease (T3+T4) was higher (OR=5.21) and LNM presence was OR=4.76 (p<0.001 and p<0.0001, respectively). None of the patients below 55 years old showed distant metastasis, but 19 patients above 55 years old showed M1 (p<0.0001). In older patients group (≥55 years old) we observed deaths related thyroid cancer in 11 individuals.Conclusions: The age cut off of 55 years old for risk stratification proposed by the 8th Edition of AJCC effectively stratifies PTC patients with a poor prognosis, indicating it is likely to be useful in clinical practice.

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