Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Molecular Features of Follicular Variant Papillary Carcinoma of Thyroid: Comparison of Areas With or Without Classical Nuclear Features

  • 290 Accesses

  • 3 Citations

Abstract

We aimed to compare the genetic background of different areas in follicular variant papillary thyroid carcinomas (FVPTC) with or without classical nuclear changes. Sixteen cases of FVPTC were included in our study. All tumors were well demarcated from surrounding thyroid tissue and had both areas with nuclear features (WNF) and areas without nuclear features (WONF) of papillary carcinoma. DNA is obtained by laser microdissection from WNF and WONF areas of each case. Point mutations for NRAS codon 61, HRAS codon 61, and BRAF were investigated by direct sequencing. In 11 cases, reverse transcription PCR was performed for the presence of PAX8-PPARɣ and RET/PTC1–3 gene rearrangements. Point mutation for NRAS codon 61 was also studied in 15 colloidal nodules. Seven cases (44 %) showed at least one mutation; two cases (13 %) revealed the same mutation in both WNF and WONF areas, while in the rest only WNF areas were mutated. None of the studied 11 cases demonstrated RET/PTC1–3 gene rearrangement and in only one case PAX8-PPARɣ gene rearrangement was found. Six cases (38 %) showed NRAS codon 61 mutation, involving only WNF areas in five cases and both WNF and WONF areas in one case. Neither HRAS codon 61 nor BRAF mutations were present. Fifteen colloidal nodules were also wild type for NRAS codon 61. Our findings suggest that NRAS codon 61 point mutations and PAX8-PPARɣ gene rearrangement play a role in the FVPTC pathogenesis and may be established before the morphological/phenotypical features fully develop.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. 1.

    2003 Thyroid cancer. In: Steward BW, Kleiheus P (eds) World cancer report. Vol. IARC Press, Lyon.

  2. 2.

    Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA 2003 High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Research 63:1454–1457.

  3. 3.

    Baloch ZW, LiVolsi VA 2007 Our approach to follicular-patterned lesions of the thyroid. Journal of Clinical Pathology 60:244–250.

  4. 4.

    Chetty R 2011 Follicular patterned lesions of the thyroid gland: a practical algorithmic approach. Journal of Clinical Pathology 64:737–741.

  5. 5.

    Ozdemir D, Ersoy R, Cuhaci N, Arpaci D, Ersoy EP, Korukluoglu B, Guler G, Cakir B 2011 Classical and follicular variant papillary thyroid carcinoma: comparison of clinical, ultrasonographical, cytological, and histopathological features in 444 patients. Endocrine Pathology 22:58–65.

  6. 6.

    Rosai J 2010 The encapsulated follicular variant of papillary thyroid carcinoma: back to the drawing board. Endocrine pathology 21:7–11.

  7. 7.

    Elsheikh TM, Asa SL, Chan JK, DeLellis RA, Heffess CS, LiVolsi VA, Wenig BM 2008 Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma. American Journal of Clinical Pathology 130:736–744.

  8. 8.

    Liu J, Singh B, Tallini G, Carlson DL, Katabi N, Shaha A, Tuttle RM, Ghossein RA 2006 Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a problematic entity. Cancer 107:1255–1264.

  9. 9.

    Williams ED 2000 Guest Editorial: Two Proposals Regarding the Terminology of Thyroid Tumors. International Journal of Surgical Pathology 8:181–183.

  10. 10.

    Rivera M, Ricarte-Filho J, Knauf J, Shaha A, Tuttle M, Fagin JA, Ghossein RA 2010 Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 23:1191–1200.

  11. 11.

    Esapa CT, Johnson SJ, Kendall-Taylor P, Lennard TW, Harris PE 1999 Prevalence of Ras mutations in thyroid neoplasia. Am J Surg Pathol 37:1586-91.

  12. 12.

    Cohen Y, Rosenbaum E, Clark DP, Zeiger MA, Umbricht CB, Tufano RP, Sidransky D, Westra WH 2004 Mutational analysis of BRAF in fine needle aspiration biopsies of the thyroid: a potential application for the preoperative assessment of thyroid nodules. Clinical cancer research: an official journal of the American Association for Cancer Research 10:2761–2765.

  13. 13.

    Nikiforova MN, Biddinger PW, Caudill CM, Kroll TG, Nikiforov YE 2002 PAX8-PPARgamma rearrangement in thyroid tumors: RT-PCR and immunohistochemical analyses. The American Journal of Surgical Pathology 26:1016–1023.

  14. 14.

    Adeniran AJ, Zhu Z, Gandhi M, Steward DL, Fidler JP, Giordano TJ, Biddinger PW, Nikiforov YE 2006 Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. The American Journal of Surgical Pathology 30:216–222.

  15. 15.

    Nikiforov YE 2002 RET/PTC rearrangement in thyroid tumors. Endocrine Pathology 13:3–16.

  16. 16.

    Tallini G, Asa SL 2001 RET oncogene activation in papillary thyroid carcinoma. Advances in Anatomic Pathology 8:345–354.

  17. 17.

    Di Cristofaro J, Marcy M, Vasko V, Sebag F, Fakhry N, Wynford-Thomas D, De Micco C 2006 Molecular genetic study comparing follicular variant versus classic papillary thyroid carcinomas: association of N-ras mutation in codon 61 with follicular variant. Human Pathology 37:824–830.

  18. 18.

    Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE 2003 Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. American Journal of Clinical Pathology 120:71–77.

  19. 19.

    Castro P, Rebocho AP, Soares RJ, Magalhaes J, Roque L, Trovisco V, Vieira de Castro I, Cardoso-de-Oliveira M, Fonseca E, Soares P, Sobrinho-Simoes M 2006 PAX8-PPARgamma rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma. The Journal of Clinical Endocrinology and Metabolism 91:213–220.

  20. 20.

    Marques AR, Espadinha C, Catarino AL, Moniz S, Pereira T, Sobrinho LG, Leite V 2002 Expression of PAX8-PPAR gamma 1 rearrangements in both follicular thyroid carcinomas and adenomas. The Journal of Clinical Endocrinology and Metabolism 87:3947–3952.

  21. 21.

    Nikiforova MN, Lynch RA, Biddinger PW, Alexander EK, Dorn GW, 2nd, Tallini G, Kroll TG, Nikiforov YE 2003 RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. The Journal of Clinical Endocrinology and Metabolism 88:2318–2326.

  22. 22.

    Bansal M, Gandhi M, Ferris RL, Nikiforova MN, Yip L, Carty SE, Nikiforov YE 2013 Molecular and histopathologic characteristics of multifocal papillary thyroid carcinoma. Am J Surg Pathol (in press)

  23. 23.

    Namba H, Rubin SA, Fagin JA 1990 Point mutations of ras oncogenes are an early event in thyroid tumorigenesis. Molecular Endocrinology (Baltimore, Md) 4: 1474–1479.

  24. 24.

    Ohori NP, Nikiforova MN, Schoedel KE, LeBeau SO, Hodak SP, Seethala RR, Carty SE, Ogilvie JB, Yip L, Nikiforov YE 2010 Contribution of molecular testing to thyroid fine-needle aspiration cytology of "follicular lesion of undetermined significance/atypia of undetermined significance". Cancer Cytopathology 118:17–23.

Download references

Acknowledgments

This study is accepted as a poster presentation in USCAP 2012 meeting, March 17–23, 2012, Vancouver, BC, Canada. This study is granted by Hacettepe University Scientific Research Unit, grant number B.30.2.HAC.0.20.05.04

Conflict of Interest

The authors declare that no competing financial interests exist.

Author information

Correspondence to Guven Guney.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Guney, G., Tezel, G.G., Kosemehmetoglu, K. et al. Molecular Features of Follicular Variant Papillary Carcinoma of Thyroid: Comparison of Areas With or Without Classical Nuclear Features. Endocr Pathol 25, 241–247 (2014). https://doi.org/10.1007/s12022-013-9275-6

Download citation

Keywords

  • Thyroid
  • Follicular variant papillary carcinoma
  • Nuclear features
  • BRAF
  • RAS
  • PAX8-PPARɣ
  • RET/PTC
  • Laser microdissection