Endocrine oncology

Cytologic and Molecular Assessment of Isthmus Thyroid Nodules and Carcinomas

ThyroidPublished Observational cohort study

Authors' conclusion

These data suggest isthmic nodules are more likely to have malignant cytology and increased rates of higher risk molecular alterations compared with lobar nodules. IF-PTC from the isthmus is molecularly different compared with IF-PTC from the lobes.

Study context

Population
Afirma thyroid nodule database; histopathology reports of papillary thyroid cancer (PTC) and infiltrative follicular subtype of PTC (IF-PTC) from Afirma discovery cohorts and a community endocrine surgery practiceAfirma database
Participants
177,227 participants
Exposure
Isthmus vs lobar thyroid nodules
  • Isthmusn = 8,527
Outcome
Bethesda V-VI nodules
Methodological detailsgenome-wide differential expression analysis
  • Genome-wide differential expression analysis

Main finding

As reported in the abstract

P < 0.0001

Observational data: associations, not effects.

Further findings

BRAFp.V600E

P < 0.0001

ALK/NTRK/RET fusions

P < 0.0001

SPOP variants

P < 0.0001

NRAS mutations

P < 0.0001

PAX8::PPARy fusions

P < 0.0001

IF-PTC: isthmus (n = 13) vs lobes (n = 181) · more BRAF-like, increased ERK and FMT scores with isthmus
P < 0.01 for all

Transcriptome signatures

Isthmus nodules had higher BRAF-like scores, ERK activity and FMT scores, and lower inflammation activity scores
Genes downregulated in isthmus tumors enriched in immune response regulation

Original publication

Cytologic and Molecular Assessment of Isthmus Thyroid Nodules and Carcinomas. Thyroid. Published 11 November 2024. doi:10.1089/thy.2024.0254

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