The role of CDKN2C copy number in sporadic medullary thyroid carcinoma.

The role of CDKN2C copy number in sporadic medullary thyroid carcinoma.

Thyroid. 2016 Sep 9;

Authors: Grubbs EG, Williams MD, Scheet P, Vattathil S, Perrier N, Lee JE, Gagel RF, Hai T, Feng L, Cabanillas M, Cote GJ

Abstract
BACKGROUND: The cyclin-dependent-kinase inhibitors (CDKN)/retinoblastoma (RB1) pathway has been implicated as having a role in medullary thyroid carcinoma (MTC) tumorigenesis. CDKN2C loss has been associated with RET-mediated MTC in humans but with minimal phenotypic correlation provided. The objective of this study was to evaluate the association among tumor RET mutation status, CDKN2C loss, and aggressiveness of MTC in a cohort of patients with sporadic disease.
METHODS: Tumors from patients with sporadic MTC treated at a single institution were evaluated for somatic RET M918T mutation and CDKN2C copy number loss. These variables were compared to patient demographics, pathology detail, clinical course, and disease-specific and overall survival.
RESULTS: Sixty-two MTC cases with an initial surgery date ranging from 1983 to 2009 met the inclusion criteria. The median age at initial surgery was 53 years (range 22-81 years) of whom 36 (58%) were male. The median tumor size was 30 mm (range 6-145 mm) with 29 (57%) possessing extrathyroidal extension. Nodal and/or distant metastasis at presentation was found in 47 of 60 (78%) and 12 of 61 (20%) of patients, respectively. Median follow up time was 10.5 years (1.1-27.8 years) for the censored observations. The presence of CDKN2C loss was associated with worse M stage and overall AJCC stage. Median overall survival of patients with vs. without CDKN2C loss was 4.14 (95% CI: 1.93-NA) vs. 18.27 (95%CI: 17.24-NA) years (p=<0.0001). Median overall survival of patients with a combined somatic RET M918T mutation and CDKN2C loss vs. no somatic RET M918T mutation and CDKN2C loss vs. somatic RET M918T mutation and CDKN2C 2N vs. no somatic RET M918T mutation and CDKN2C 2N was 2.38 (95% CI: 1.67-NA) years vs. 10.81 (95% CI: 2.46-NA) vs. 17.24 (95% CI: 9.82-NA) vs. not reached (95% CI: 13.46-NA) years (p=<0.0001).
CONCLUSIONS: The presence of CDKN2C loss is associated with the presence of distant metastasis at presentation as well decreased overall survival, a relationship enhanced by concomitant RET M918T mutation. Further defining the genes involved in the progression of metastatic MTC will be an important step towards identifying pathways of disease progression and new therapeutic targets.

PMID: 27610696 [PubMed - as supplied by publisher]

from #ENT-PubMed via ola Kala on Inoreader http://ift.tt/2ct1lxy
via IFTTT