After analyzing the RNA-Seq data of PTC patients from the Cancer Genomic Atlas, 497 differentially expressed PTC genes were found to be associated with HT, of which protein tyrosine phosphatase receptor type C (PTPRC), KIT, and COL1A1 were associated with tumor size and lymph node metastasis (p < 0.05).
In addition, several clinicopathological factors such as age ≥45 years, VI, ETE, and LNM were shown to be significant risk factors for DM in both PTC and FTC subgroups.
The multifocality rate of PTC was 35.1% and mPTC were shown to have larger primary tumor diameter, higher rate of lymph node metastasis and less number of accompanying non-cancerous lesions than single PTC in one or both gender groups.
Comparing the cytological or, when performed, histological diagnoses with the results of FNAB-Tg, we found that in 24 cases of lymph node metastases from PTC (19 lymph nodes from patients at the first diagnoses and 5 lymph nodes from PTC patients in follow up) the mean level of Thyroglobulin was 1840.11 ng/ml; range: <0,2 to 11440 ng/ml.
In addition, in PTMC patients with EI and/or LNM and/or positive BRAF (high-risk PTMC patients), the prevalence of extrathyroidal invasion, Hashimoto's disease, lymph node metastasis, tumor TNM stage, PEDF positive protein expression, the rate of recurrent disease, and the mRNA expression of anti-angiogenic factors was almost as high as in patients with larger PTC, but with no significant difference.
One asymptomatic carrier had de novo codon 918 mutation (MEN2B) and showed bilateral microcarcinoma with lymph node metastasis at presentation and progressive disease on follow-up.
Positive associations were found between levels of miR-146a expression in PTC tissues and gender (female), cervical lymph node metastasis, multifocality, extra tyroidal invasion and advanced clinical TNM stages (III and IV).
Genome-wide copy number analysis in a family with p.G533CRET mutation and medullary thyroid carcinoma identified regions potentially associated with a higher predisposition to lymph node metastasis.
In the present work, a comparative genomic hybridization (CGH) study was performed using DNA from a primary tumor in a M918TRET mutation-positive SMTC patient and from its lymph node metastasis to investigate additional genetic alterations.
The closer mutations in codon 620, 618, and 611 were located to the transmembrane domain (codons 657-636) of the RET receptor, the greater were mean primary tumor diameters (23.5, 18.7, and 7.5 mm, P=0.020), the frequency of lymph node metastasis (75, 68, and 30%, P=0.11) and pheochromocytoma (38, 16, and 0%, P=0.11).
More interestingly, the presence of a somatic RET mutation correlates with the presence of lymph node metastases at diagnosis, which is a known bad prognostic factor for the definitive cure of MTC patients.
RET/PTC rearrangements presented at younger age and had predominantly typical papillary histology, frequent psammoma bodies, and a high rate of lymph node metastases.
To our knowledge, this case represents the first documented case of concurrent lymph node metastases of MTC and PTC in a patient with RET proto-oncogene germline mutation.