title: Medullary thyroid carcinoma: long-term outcomes of surgical treatment.
abstract: 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.
authors.affiliation: Department of Surgery, University Clinic, Royal North Shore Hospital, University of Sydney Endocrine Surgical Unit, St Leonards, Sydney, NSW, Australia.
authors.forename: Deepak T
authors.initials: DT
authors.lastname: Abraham
authors.forename: Tsu-Hui
authors.initials: TH
authors.lastname: Low
authors.forename: Marinella
authors.initials: M
authors.lastname: Messina
authors.forename: Nicole
authors.initials: N
authors.lastname: Jackson
authors.forename: Anthony
authors.initials: A
authors.lastname: Gill
authors.forename: Angela S
authors.initials: AS
authors.lastname: Chou
authors.forename: Leigh
authors.initials: L
authors.lastname: Delbridge
authors.forename: Diana
authors.initials: D
authors.lastname: Learoyd
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Robinson
authors.forename: Stan
authors.initials: S
authors.lastname: Sidhu
authors.forename: Mark
authors.initials: M
authors.lastname: Sywak
mesh_terms: 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
chemical_list: 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