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Abstract
Background. The clinical importance of point mutations of ras oncogene in differentiated thyroid
cancers has not been fully clarified. The purpose of this study is to determine the
prognostic importance of ras mutation in papillary thyroid carcinoma.
Methods. Tumors of 91 patients with papillary carcinoma were studied; mean follow-up was 14.1
years (range, 1 to 40 years). Patients were grouped as follows: class I, intrathyroidal
disease, n = 21; class II, cervical node metastases, n = 22; class III, extrathyroidal
disease; n = 19; and class IV, distant metastases, n = 29. DNA was analyzed with polymerase
chain reaction, oligonucleolide hybridization, and DNA sequence analysis techniques.
Results. Thirteen (14.3%) of 91 tumors showed an N-ras point mutation: 4.8% (1 of 21) patients
in class 1; 4.5% (1 of 22) patients in class II; 15.8% (3 of 19) patients in class
III; and 27.8% (8 of 29) patients in class IV. Each mutation changed colon 67 from
glutamine to arginine. Patients with distant metastases (8 of 29) had a significantly
higher incidence of ras mutations than others (5 of 62, p = 0.01) . Patients in classes
III and IV also had a higher incidence of mutations (11 of 48) than patients in classes
I and II (2 of 43, p = 0.01). The incidence of ras mutations was significantly higher
in patients who died of papillary cancer (5 of 15, 33.3%) than in patients who are
still alive (8 of 76, 10.5%) (p = 0.02). Kaplan-Meier survival curves also showed
a greater mortality from tumor (p < 0.05) and a higher recurrence rate (p < 0.01)
in ras-positive tumors than in the ras-negative group. Finally, in studies by multivariate
analyses, positive ras mutation and age were shown to be two independent prognostic
factors for prediction of death from papillary cancer and recurrence of cancer.
Conclusions. Mutation of N-ras gene at colon 61 is an independent prognostic factor for aggressiveness
of papillary thyroid carcinomas.
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Article info
Footnotes
☆Supported by the Nathan and Frances Goldblatt Society for Cancer Research.
☆☆Presented at the Fifteenth Annual Meeting of the American Association of Endocrine Surgeons, Dearborn, Mich., April 17–19, 1994.
Identification
Copyright
© 1994 Published by Elsevier Inc.
