Clinical and molecular features of papillary thyroid cancer in adolescents and young adults

Abstract

Background: Age disparities in thyroid cancer incidence and outcome among adolescents and young adults (AYAs) with thyroid cancer are under reported. In this study, the authors compared the molecular and clinical features of papillary thyroid cancer (PTC) in AYAs with the same features among patients in other age groups.

Methods: One thousand eleven patients underwent initial treatment for PTC at the University of California at San Francisco. Patients were subdivided into 2 age groups: ages 15 to 39 years (the AYA group) and aged ≥40 years. Demographic, clinical, and survival data in the cohort also were compared with data from the National Cancer Instsitute's Surveillance, Epidemiology, and End Results (SEER) Program. In a subset of the study cohort, the primary tumors were analyzed by genome-wide expression analyses, genotyping for common somatic mutations, and pathway-specific gene expression arrays between the age groups.

Results: The percentage of women and the lymph node metastasis rate were significantly higher in the AYA group. In the AYA group, the rate of distant metastasis was lower. Disease-free survival and median overall survival were significantly higher in the AYA group. The better survival in AYA patients also was apparent in the national SEER data. An unsupervised cluster analysis of gene expression data revealed no distinct clustering by age in 96 PTC samples. The frequency and type of somatic mutations in the primary tumors did not differ significantly between age groups (the AYA group vs the group aged ≥40 years). Six genes (extracellular matrix protein 1 [ECM1], v-erb-2 erythroblastic leukemia viral oncogene homolog 2 [ERBB2], urinary plasminogen activator [UPA], 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 [PFKFB2], meis homeobox 2 [MEIS2], and carbonic anhydrase II [CA2]) had significant differential expression between age groups.

Conclusions: The extent of disease at presentation and the survival of patients with PTC differed between AYAs and older patients. The current results indicated that these differences may be caused by several candidate genes and that these genes are expressed differentially and may play an important role in tumor cell biology. However, no distinct gene expression profiles exist for patients with PTC that distinguish between AYAs and patients aged ≥40 years.

Figure 1

Disease-free (A) and overall survival (B) (in years) in patients with PTC, by age group, for patients treated at UCSF. (C) Overall survival (in years), by age group, for SEER data.

Figure 1

Disease-free (A) and overall survival (B) (in years) in patients with PTC, by age group, for patients treated at UCSF. (C) Overall survival (in years), by age group, for SEER data.