PubMed · 2085366
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B Franc. 1990. [Papillary thyroid cancer, diffuse sclerosing variant].. https://pubmed.ncbi.nlm.nih.gov/2085366/
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Papillary thyroid carcinoma (PTC) is associated with RET and NTRK1 rearrangements and BRAF mutations. A series of 60 PTCs collected in a single center from Italian patients were histologically re-examined and subclassified as well differentiated or tall cell variant. The sample collection was analysed for the presence of all the reported PTC-associated genetic alterations through DNA or cDNA amplification, followed by automated sequencing. The analysis of exons 11 and 15 of BRAF gene revealed the T1796A (V599E) mutation in 32% of cases, and this alteration is significantly associated with PTC tall cell variant. Oncogenic rearrangements of RET and NTRK1 receptors were found in 33 and 5% of cases, respectively. No Ras mutations were detected. Overall, genetic alterations were detected in two-thirds of samples, and in no single case more than one mutational event was found simultaneously. Gene expression profiling of a subset of 31 tumors performed using cDNA microarray chips showed no strong differences in global gene expression among the different cases. However, a supervised analysis of the obtained data identified a subset of genes differentially expressed in tumors carrying BRAF mutation or RTK rearrangement.
Somatic mutations of the BRAF gene (BRAFV599E and BRAFK600E) were found to be closely associated with different histotypes of papillary thyroid carcinoma (PTC). The V599E mutation is highly prevalent in PTC with a papillary or mixed papillary follicular growth pattern, and the K600E mutation is apparently restricted to the follicular variant of PTC. It is usually accepted that thyroid malignancies may follow a progression path from well-differentiated to poorly differentiated (PDC) and undifferentiated (UC) carcinomas. One would expect that at least some of the less differentiated carcinomas would harbour the genetic alterations of pre-existing well-differentiated tumours. In order to find the prevalence of BRAF mutations in PDC and UC, we screened a series of 19 PDCs and 17 UCs, as well as 3 UC-derived cell lines, for both mutation types. The group of PDCs was restricted to the so-called insular and insular-like PDCs, thus excluding PTCs with solid, insular or trabecular foci of growth and PDCs displaying typical PTC nuclei. No BRAF mutations were detected in any of the 19 cases of PDC, whereas 6 of the UCs (35%) and one UC-derived cell line presented the BRAFV599E mutation. The BRAFK600E mutation was not detected in any case. We conclude that UC may progress from BRAFV599E-mutated PTC. The absence of BRAF mutations in our series of PDC supports the assumption that pure insular and insular-like PDCs are more closely related to follicular carcinoma than to PTC.
HYPOTHESIS: The prognosis of papillary thyroid carcinoma has been stratified into low- and high-risk groups. Patients in the high-risk group can be substratified on the basis of increasing age, with implications for prognosis and treatment. DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENTS: A total of 727 patients with papillary thyroid cancer treated at Lahey Clinic, Burlington, Mass, from 1940 to 1998. INTERVENTIONS: Stratification into low- and high-risk groups based on age, metastases, extent, and size. High-risk patients were substratified into "younger" and "older" high-risk groups by age younger than 60 years or 60 years and older, respectively. Effects of surgery, lymph node dissection, and radiation therapy were examined. Main Outcome Measure Survival. RESULTS: Of the 727 patients, 585 (80.5%) were classified as low risk and 142 (19.5%) as high risk. The 20-year survival was 97.8% in low-risk patients and 61.3% in high-risk patients (P<.001); it was 72.3% in the younger high-risk group and 45.1% in the older high-risk group (P<.001). Older high-risk patients had a survival advantage with bilateral thyroidectomy: 54.7% 20-year survival for those undergoing bilateral thyroidectomy and 25.0% for unilateral thyroidectomy (P =.004). In the older high-risk group, patients with lymph node dissection (n = 22) had a 20-year survival of 72.4% vs 30.2% in patients who did not undergo lymph node dissection (n = 38) (P =.03). Twenty-year survival in low-risk, younger high-risk, and older high-risk patients receiving radioactive iodine vs no radiation was 100% vs 97.6% (P =.24), 64.2% vs 73.2% (P =.53), and 44.7% vs 44.4% (P =.53). CONCLUSIONS: Papillary thyroid carcinoma in low-risk patients had a favorable prognosis regardless of treatment. Older high-risk patients had a survival benefit with total thyroidectomy and lymph node dissection. Radioactive iodine did not affect 20-year survival in any of the risk groups.