Medullary Thyroid Carcinoma: Long-Term Outcomes of Surgical Treatment

• Published in: Annals of surgical oncology 2011-01, Vol.18 (1), p.219-225
• Main Authors: Abraham, Deepak T., Low, Tsu-Hui, Messina, Marinella, Jackson, Nicole, Gill, Anthony, Chou, Angela S., Delbridge, Leigh, Learoyd, Diana, Robinson, Bruce G., Sidhu, Stan, Sywak, Mark
• Format: Article
• Language: English
• Subjects: Adult; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Calcitonin - blood; Carcinoma, Neuroendocrine; Cohort Studies; Cyclin-Dependent Kinase Inhibitor p18 - genetics; DNA, Neoplasm - genetics; Endocrine Tumors; Female; Follow-Up Studies; Genetic Association Studies; Humans; Lymphatic Metastasis; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation - genetics; Oncology; Polymerase Chain Reaction; Prospective Studies; Proto-Oncogene Proteins c-ret - genetics; Retrospective Studies; Surgery; Surgical Oncology; Survival Rate; Thyroid Neoplasms - genetics; Thyroid Neoplasms - mortality; Thyroid Neoplasms - surgery; Thyroidectomy; Treatment Outcome
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-010-1339-y

Background Medullary thyroid carcinoma (MTC) accounts for 5 to 10% of all thyroid cancers but is responsible for a disproportionate number of deaths. Methods We performed a retrospective review to describe clinical outcomes in patients with medullary thyroid carcinoma, screening a subset of patients for somatic mutations in the RET and p18 genes and performing genotype-phenotype correlation in a tertiary-care referral hospital from 1967 to 2009. Results We studied a total of 94 patients identified from a prospectively maintained thyroid cancer database. Data gathered included patient demographics, serum calcitonin, clinical outcomes, histopathology, genetic analysis, and status at final follow-up. A subset cohort ( n  = 50) was screened for somatic mutations in the RET gene and the three exons of the p18 gene. The subset cohort was composed of hereditary medullary thyroid carcinoma (HMTC) ( n  = 19, index patients = 10, screen detected = 9) and sporadic medullary thyroid carcinoma (SMTC) ( n  = 31). There were no mutations in the p18 gene in the subset cohort. Conclusions A total of 67 SMTC and 27 (28.7%) HMTC cases identified. SMTC were older at initial presentation (52 vs. 34, P  = 0.003), had higher preoperative serum calcitonin levels (7968 vs. 1346 ng/L, P  = 0.008), and had lymph node recurrence ( P  = 0.001) compared to HMTC. The tumors were smaller in HMTC ( P  = 0.038). Overall 10-year survival in SMTC versus HMTC was 69 versus 93% ( P  = 0.12). On multivariate analysis, vascular invasion (hazard ratio 6.4, P  = 0.019) was an adverse predictor for disease-free survival. HMTC in the era of RET analysis presents with a smaller primary tumor, lower preoperative serum calcitonin levels, and lower rates of lymph node metastasis. Mutations in the p18 gene were not a major factor in medullary thyroid carcinoma tumorigenesis.