Molecular Profile and Clinical-Pathologic Features of the Follicular Variant of Papillary Thyroid Carcinoma: An Unusually High Prevalence of ras Mutations

Departments of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, 231 Albert Sabin Way, PO Box 670529, Cincinnati, OH 45267-0529, USA.
American Journal of Clinical Pathology (Impact Factor: 3.01). 08/2003; 120(1):71-7. DOI: 10.1309/ND8D-9LAJ-TRCT-G6QD
Source: PubMed

ABSTRACT The follicular variant (FV) of papillary thyroid carcinoma is characterized by a follicular growth pattern and cytologic features of papillary carcinoma. ret/PTC rearrangements are common in classic papillary thyroid carcinoma (PTC) and PAX8-PPAR gamma and ras mutations in follicular thyroid carcinoma. Their prevalence in FV has not been established. We studied these genetic alterations and clinical-pathologic features in 30 FV cases and compared those with 46 non-FV papillary carcinomas. FV cases revealed 1 ret/PTC rearrangement (3%) and 13 ras mutations (43%). Non-FV cases harbored 13 ret/PTC (28%) (P = .006) and no ras mutations (P = .0002). No PAX8-PPAR gamma was found in either group. FV cases demonstrated a significantly higher prevalence of tumor encapsulation, angiovascular invasion, and poorly differentiated areas and a lower rate of lymph node metastases. These data indicate that the FV of papillary carcinoma has a distinct set of molecular alterations and is characterized by a high frequency of ras point mutations.

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    • "Author Age From time of initial treatment Variant Treatment Survival after diagnosis of pancreatic metastasis Zhu et al. [4] NA NA Tall cell Surgical resection NA Sugimura et al. [5] 53 years 7 years after TT + RAI Classical Surgical resection NA Jobran et al. [6] 53 years male NA Tall cell Surgical resection NA Angeles-Angeles et al. [7] 72 years male NA Classical Surgical resection NA Borschitz et al. [8] 34 years female 9 years after TT + RAI Classical Surgical resection 42 months 46 years male 2 years after TT + RAI Follicular Chen and Brainard [9] 82 years male 5 years after TT + RAI Classical Surgical resection NA Alzahrani et al. [10] 56 years male 6 years after TT + RAI Classical Sorafenib 20 months Present case 67 years 7 years after TT + RAI Tall cell Surgical resection and RAI Alive at 32 months TT: total thyroidectomy, RAI: radioactive iodine therapy, NA: not mentioned. pancreatic metastases are usually sign of extensive disease seen in our patient. "
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    ABSTRACT: Introduction. Follicular variant (FV) papillary thyroid carcinoma (PTC) has aggressive biologic behavior as compared to classic variant (CV) of PTC and frequently metastasizes to the lungs and bones. However, metastasis to the pancreas is extremely rare manifestation of FV-PTC. To date, only 9 cases of PTC have been reported in the literature. Pancreatic metastases from PTC usually remain asymptomatic or manifest as repeated abdominal aches. Associated obstructive jaundice is rare. Prognosis is variable with reported median survival from 16 to 46 months. Case Presentation. Herein we present a 67-year-old Saudi woman, who developed pancreatic metastases seven years after total thyroidectomy and neck dissection followed by radioactive iodine ablation (RAI) for FV-PTC. Metastasectomy was performed by pancreaticoduodenectomy followed by sorafenib as genetic testing revealed a BRAF V600E mutation. She survived 32 months after the pancreatic metastasis diagnosis. Conclusion. Pancreatic metastases are rare manifestation of FV-PTC and are usually sign of extensive disease and conventional diagnostic tools may remain to reach the diagnosis.
    03/2013; 2013:386263. DOI:10.1155/2013/386263
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    • "There is preliminary evidence that FVPTC has genotypic differences to CPTC that lead to the phenotypic difference between these 2 entities. For instance, data from our group and others have shown that FVPTC differs from CPTC by showing fewer RET, p16 alterations, less COX-2 expression, and more RAS genetic alterations [7] [8] [9] [10] [11]. However, the number of cases analyzed in many studies was small. "
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    ABSTRACT: Mutation of the BRAF gene is common in thyroid cancer. Follicular variant of papillary thyroid carcinoma is a variant of papillary thyroid carcinoma that has created continuous diagnostic controversies among pathologists. The aims of this study are to (1) investigate whether follicular variant of papillary thyroid carcinoma has a different pattern of BRAF mutation than conventional papillary thyroid carcinoma in a large cohort of patients with typical features of follicular variant of papillary thyroid carcinoma and (2) to study the relationship of clinicopathological features of papillary thyroid carcinomas with BRAF mutation. Tissue blocks from 76 patients with diagnostic features of papillary thyroid carcinomas (40 with conventional type and 36 with follicular variant) were included in the study. From these, DNA was extracted and BRAF V600E mutations were detected by polymerase chain reaction followed by restriction enzyme digestion and sequencing of exon 15. Analysis of the data indicated that BRAF V600E mutation is significantly more common in conventional papillary thyroid carcinoma (58% versus 31%, P = .022). Furthermore, the mutation was often noted in female patients (P = .017), in high-stage cancers (P = .034), and in tumors with mild lymphocytic thyroiditis (P = .006). We concluded that follicular variant of papillary thyroid carcinoma differs from conventional papillary thyroid carcinoma in the rate of BRAF mutation. The results of this study add further information indicating that mutations in BRAF play a role in thyroid cancer development and progression.
    Human pathology 12/2010; 42(4):500-6. DOI:10.1016/j.humpath.2009.09.023 · 2.81 Impact Factor
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    • "Three Ras proto-oncogenes — HRAS, KRAS, and NRAS — are implicated in human tumorigenesis (Downward 2003). Ras mutations are more common in iodinedeficient than iodine-sufficient areas and in lesions with follicular architecture (including follicular carcinoma and follicular variant papillary thyroid carcinoma) than in typical papillary thyroid carcinoma (Shi et al. 1991, Zhu et al. 2003) and highly specific analysis indicates that Ras mutations are more common in poorly differentiated and undifferentiated thyroid carcinoma, implicating this phenomenon in tumour progression (Ezzat et al. 1996, Garcia- Rostan et al. 2003). Another FTC group presents the fusion of two nuclear proteins with transcriptional activity: PAX8 and peroxisome proliferatoractivated receptor J (PPARJ; Kroll et al. 2000; Table 2). "
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