title: Tumorigenesis of papillary thyroid cancer is not BRAF-dependent in patients with acromegaly.
abstract: BACKGROUND
  Several studies have reported a high frequency of papillary thyroid cancer (PTC) in patients with acromegaly. The aim of this study was to determine the prevalence and predictors of thyroid cancer in patients with acromegaly and to investigate the frequency of the BRAFV600E mutation in PTC patients with and without acromegaly.
  
  
  METHODS
  We conducted a retrospective study of 60 patients with acromegaly. Thyroid ultrasonography (US) and US-guided fine needle aspiration were performed on nodules with sonographic features of malignancy. We selected 16 patients with non-acromegalic PTC as a control group. The BRAFV600E mutation was analyzed in paraffin-embedded surgical specimens of PTC by real-time polymerase chain reaction, and tumor specimens from patients with PTC were stained immunohistochemically with an antibody against insulin-like growth factor-1 receptor β (IGF-1Rβ).
  
  
  RESULTS
  Thyroid cancer was found in 15 (25.0%) patients. No differences in age, sex, initial growth hormone (GH) and IGF-1 percentage of the upper limit of normal values or treatment modalities were observed between patients with and without PTC. Acromegaly was active in 12 of 15 patients at the time of PTC diagnosis; uncontrolled acromegaly had a significantly higher frequency in the PTC group (60%) than in the non-PTC group (28.9%) (p = 0.030). The BRAFV600E mutation was present in only 9.1% (1/11) of PTC patients with acromegaly, although 62.5% (10/16) of control patients with PTC had the mutation (p = 0.007). IGF-1Rβ immunostaining showed moderate-to-strong staining in all malignant PTC cells in patients with and without acromegaly. Significantly less staining for IGF-1Rβ was observed in normal adjacent thyroid tissues of PTC patients with acromegaly compared with those without (p = 0.014).
  
  
  CONCLUSIONS
  The prevalence of PTC in acromegalic patients was high (25%). An uncontrolled hyperactive GH-IGF-1 axis may play a dominant role in the development of PTC rather than the BRAFV600E mutation in patients with acromegaly.
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Ji Shin
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Surgery, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Park
authors.affiliation: Department of Surgery, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Jin Seong
authors.initials: JS
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Jee Hee
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Ho-Cheol
authors.initials: HC
authors.lastname: Kang
mesh_terms: D000172:Acromegaly / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D000328:Adult; D063646:Carcinogenesis / Q000235:genetics*; D002277:Carcinoma / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D002291:Carcinoma, Papillary; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000150:complications / Q000175:diagnosis / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf