Abstract B76: Thyroid cancer ethnic disparity in Hawaii: BRAF mutation within the Filipino population
Authors: Morita Shane Y. , Grace Chelestes K. , Lum Christopher A. , Davis James W. 
Published: June 2012

Background: The incidence of thyroid cancer is rapidly progressing in the United States, with the vast majority attributed to papillary thyroid carcinoma (PTC). In Hawaii, Filipinos comprise the largest group affected by this malignancy. Although generally perceived to be indolent, previous investigators have noted that Filipinos with thyroid cancer have a higher recurrence rate. Interestingly, biologic factors to explicate this disparity have not been fully elucidated. The prevalence of the BRAF mutation in PTC is approximately 45% and has been associated with an aggressive phenotype as well as an adverse prognosis. However, molecular profiling for this somatic mutation within the Filipino PTC population has not been conducted. The Pacific Basin provides a unique opportunity to study diseases in distinct ethnic groups. We elected to examine the frequency of the BRAF mutation in PTC within the Filipino population here in Hawaii.

Methods: IRB approval was obtained for this retrospective analysis. From 1992–2006, 37 Filipino patients histologically confirmed to have conventional PTC were evaluated at a tertiary care medical center. Data including age, gender, tumor size, subtype, extrathyroidal extension, multifocality, lymph node involvement, presence of distant metastasis, and American Joint Committee on Cancer (AJCC) stage were compiled. Detection for the BRAF somatic mutation was performed on formalin-fixed/ paraffin-embedded archived surgical biospecimens. Tumor DNA was isolated via laser capture microdissection and ascertained by a microarray chip containing a panel of selected V600 BRAF point mutations, including A, D, E1, E2, and KRM. Comparison of the average BRAF frequency as reported in the literature versus our study cohort was done by binomial proportion analysis. Five-year survival was calculated by the Kaplan-Meier method. Fisher's exact test was used to determine if extrathyroidal extension was a predictor for the BRAF mutation.

Results: Our findings demonstrated that 31/37 (83.8%) of our patients harbored the BRAF mutation and were exclusively the V600E1 variant. This was statistically significant with a p-value of &lt;0.001. Additionally, 5-year survival for our cohort was only 84.2%. Demographics of the Filipino population included mean age of 47 years old (range 21–87) and female gender 28/37 (76%). All patients possessed the conventional subtype of PTC; those with aggressive histologies such as tall-cell or insular were excluded. The average tumor size was 2.1 cm (range 0.4–6.0); extrathyroidal extension was 23/37 (62%), multifocality 18/37 (49%), lymph node involvement 17/37 (46%), while presence of distant metastasis was only 2/37 (5%). AJCC stage distribution was I=19/37 (51%), II=4/37 (11%), III=11/37 (30%), and IV=3/37 (8%). Eleven patients (11/14 i.e. 78.6%) did not possess extrathyroidal extension, although they were BRAF mutant. There was no association between extrathyroidal extension and BRAF mutation (p-value 0.65).

Conclusions: Filipino patients with conventional PTC were unequivocally found to have a high preponderance of the BRAF mutation (83.8%) when compared to the norm in the literature (45%). Although extrathyroidal extension has historically been documented as a predictor for BRAF mutation, we did not find this association in our study. Despite the fact that half of our cohort had stage I disease, five-year survival was lower with respect to the literature. This is the first study to our knowledge that has profiled the BRAF mutation in a Filipino population of PTC patients. This is compelling data that may be applied to the metastatic phenotype in future trials and advocates the potential utility of ethnicity as a legitimate prognostic variable. More importantly, this supports the concept of conducting ethnic disparities research in understudied populations such as the Filipinos, who have increased in number by nearly 40% in the U.S.

Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B76.