Medullary thyroid carcinoma: long-term outcomes of surgical treatment.
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.
Abraham
Deepak T
DT
Department of Surgery, University Clinic, Royal North Shore Hospital, University of Sydney Endocrine Surgical Unit, St Leonards, Sydney, NSW, Australia.
Low
Tsu-Hui
TH
Messina
Marinella
M
Jackson
Nicole
N
Gill
Anthony
A
Chou
Angela S
AS
Delbridge
Leigh
L
Learoyd
Diana
D
Robinson
Bruce G
BG
Sidhu
Stan
S
Sywak
Mark
M
D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D002116:Calcitonin / Q000097:blood; D018278:Carcinoma, Neuroendocrine; D015331:Cohort Studies; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D012189:Retrospective Studies; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000235:genetics / Q000401:mortality* / Q000601:surgery*; D013965:Thyroidectomy; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C493971:CDKN2C protein, human; D050763:Cyclin-Dependent Kinase Inhibitor p18; D004273:DNA, Neoplasm; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human