Background
The role of the B-isoform of the Raf kinase (BRAF) mutation BRAFV600E as an independent prognostic factor in papillary thyroid cancer (PTC) remains controversial.
Some studies suggest that tumors containing BRAFV600E have decreased radioiodine avidity and present a greater risk of nodal recurrence
and distant metastases.
Methods
Paraffin-embedded specimens from consecutive patients who underwent surgery for PTC
before 2003 were independently reviewed by an endocrine pathologist. DNA was extracted,
amplified by polymerase chain reaction, and the presence of the BRAFV600E mutation was determined by restriction digest. Tumor characteristics and long-term
disease outcomes were analyzed according to BRAFV600E status.
Results
BRAFV600E was identified in 60 (59%) of 101 patients. At a median follow-up of 106 months,
the overall disease-free survival was 78%. Clinically evident nodal recurrence occurred
in 11% of BRAFV600E-positive patients, and all patients required lateral neck dissection (P = .02). In contrast, subclinical nodal recurrence occurred in 7% of BRAFV600E-negative patients, and all recurrences were successfully ablated with radioactive
iodine. There was a trend toward poorer disease-free survival among patients with
stage III/IV PTC and BRAFV600E mutation (P = .08). All 5 disease-related deaths occurred in patients with BRAFV600E-positive primary tumors (P = .06).
Conclusion
The BRAFV600E mutation in PTC is associated with an increased risk of palpable nodal recurrence
and the need for reoperative surgery.
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References
- Increasing incidence of thyroid cancer in the United States, 1973-2002.JAMA. 2006; 295: 2164-2167
- Thyroid Cancer in New South Wales.Cancer Institute NSW, Sydney (Australia)2008
- Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer.Am J Med. 1994; 97: 418-428
- Papillary thyroid cancer: surgical management of lymph node metastases.Curr Treat Options Oncol. 2005; 6: 311-322
- Papillary thyroid carcinoma with distant metastases: survival predictors and the importance of local control.Surgery. 2008; 143: 35-42
- Prognostic factors associated with the survival of patients developing loco-regional recurrences of differentiated thyroid carcinomas.J Clin Endocrinol Metab. 2004; 89: 5362-5368
- Staging systems for papillary thyroid carcinoma: a study of 2 tertiary referral centers.Ann Surg. 2007; 246: 114-121
- BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications.Endocr Rev. 2007; 28: 742-762
- Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid: a meta-analysis.Cancer. 2007; 110: 38-46
- Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers.J Clin Endocrinol Metab. 2003; 88: 4393-4397
- Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas.Am J Surg Pathol. 2006; 30: 216-222
- BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas.J Clin Endocrinol Metab. 2003; 88: 5399-5404
- BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer.J Clin Endocrinol Metab. 2005; 90: 6373-6379
- The BRAF mutation is useful for prediction of clinical recurrence in low-risk patients with conventional papillary thyroid carcinoma.Clin Endocrinol (Oxf). 2006; 65: 364-368
- Association of BRAF V600E mutation with poor clinicopathological outcomes in 500 consecutive cases of papillary thyroid carcinoma.J Clin Endocrinol Metab. 2007; 92: 4085-4090
- The prevalence and prognostic value of BRAF mutation in thyroid cancer.Ann Surg. 2007; 246: 466-470
- BRAF mutations in an Italian cohort of thyroid cancers.Clin Endocrinol (Oxf). 2004; 61: 239-243
- BRAF(V599E) mutation is the leading genetic event in adult sporadic papillary thyroid carcinomas.J Clin Endocrinol Metab. 2004; 89: 2414-2420
- BRAF mutation in papillary thyroid carcinoma in a Japanese population: its lack of correlation with high-risk clinicopathological features and disease-free survival of patients.Endocr J. 2009; 56: 89-97
- BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study.J Clin Endocrinol Metab. 2008; 93: 3943-3949
- The oncogene BRAF V600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I- targeting to the membrane.Endocr Relat Cancer. 2006; 13: 257-269
- BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism.J Clin Endocrinol Metab. 2007; 92: 2840-2843
- DeLellis R.A. Lloyd R.V. Heitz P.U. Heng C. World Health Organization classification of tumours: pathology and genetics of tumours of endocrine organs. IARC Press, Lyon (France)2004
- Frequency of BRAF T1796A mutation in papillary thyroid carcinoma relates to age of patient at diagnosis and not to radiation exposure.J Pathol. 2005; 205: 558-564
- Routine ipsilateral level VI lymphadenectomy reduces postoperative thyroglobulin levels in papillary thyroid cancer.Surgery. 2006; 140: 1000-1005
Article info
Publication history
Accepted:
September 14,
2010
Footnotes
Supported by in part from research grants from the New South Wales Cancer Institute (to C.J.O. and S.B.S.) and the Cancer Council of New South Wales (to M.B. and R.C-B.).
The first two authors contributed equally to this publication.
Identification
Copyright
© 2010 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
