Indolent, aggressive papillary thyroid microcarcinomas have distinct molecular profiles

LAKE BUENA VISTA, Fla. — Indolent and aggressive papillary thyroid microcarcinomas exhibited distinct molecular profiles that may aid in diagnosis and therapeutic options, according to research presented at the International Thyroid Congress.

Papillary microcarcinoma of the thyroid gland (PMC) has a disease-specific mortality rate of less than 1%, which has led certain clinicians to suggest that the disease requires no treatment.

“Well over 99% of microcarcinoma cases are indolent,” Nikoletta Sidiropoulos, MD, assistant professor and director of molecular pathology at University of Vermont Medical Center, said during a presentation. “As imaging technology improves, smaller and smaller tumors are sampled. Coming out of medical school, we sometimes joke that PMC is the ‘good kind of cancer’ to have, but in reality, there is no good kind of cancer.”

The uncertainty of which cases of PMC will progress to metastatic disease has led to relatively uniform management based on current guidelines. Thus, rare cases of PMC may be undertreated and subject to excessive morbidity on retreatment, whereas most patients may be over-treated and at risk for unnecessary morbidity, according to study background.

Sidiropoulos and colleagues sought to determine whether distinct molecular mechanisms characterized indolent and aggressive PMCs.

They performed comparative short, noncoding RNA (ncRNA) analyses on RNA extracted from 17 patients with PMC (indolent, n = 8; aggressive, n = 9).

The researchers observed that 18 ncRNAs significantly altered indolent primary tumors when compared with matched normal tissues, whereas 34 ncRNAs altered aggressive primary tumors. Of those 52 ncRNAs, nine were unique to indolent tumors and 25 were unique to aggressive tumors.

In a direct comparison of miR profiles between indolent and aggressive tumors, the researchers observed 12 significantly altered miRs, which targeted 622 mRNAs associated with tumorigenesis. These included miR-16-5p, miR-1991-3p and miR-96-5p, whose targets included MAPK, RAS, PI3K, WNT and pluripotency transcription factors including NANOG.

In an analysis of aggressive tumors, the researchers found that aggressive tumors, metastatic tumors and normal tissue had distinct profiles. Of note, 410 ncRNAs significantly altered metastatic tumors compared with aggressive primary tumor sites, indicating a distinct molecular profile in the metastatic site.

“As a pathologist, I believe it is important for us to try and refine our diagnoses as much as possible,” Sidiropoulos said. “With increased sample size, this pilot data may prove to contribute to aiding and refining diagnosis and treatment of PMC in the future. Moving forward, we plan to complete our exome analysis.” – by Cameron Kelsall

Reference:

Sidiropoulos N, et al. Short Call Oral Abstract 4. Presented at: International Thyroid Congress; Oct. 18-23, 2015; Lake Buena Vista, Fla.

Disclosure: Sidiropoulos reports no relevant financial disclosures. HemOnc Today was unable to obtain a list of all other researchers’ relevant financial disclosures at time of reporting.