jsmc-10126

BRAF GENE MUTATION AND CD56 IMMUNOEXPRESSION IN PAPILLARY THYROID CARCINOMA IN DUHOK-IRAQ  

Ahmed Mohammad Salih a, Mowafaq Masood Naqshabandi a, Narmeen Adalat Hassan a, b, Djwar Ali Hadji c, Intisar Salim Pity a, Wan Mohammad Al-Dohoky d 

and Rawaa Salim Pity e 

a College of Medicine, University of Duhok, Duhok, Iraq.

c Department of Pathology, Directorate of health, Duhok, Iraq.

d Directorate of Health, Duhok, Iraq.

e Directorate of Health, Mosul, Iraq.   

Submitted: 27/2/2017; Accepted: 15/10/2017; Published: 1/11/2017

DOI Link: https://doi.org/10.17656/jsmc.10126

ABSTRACT

Background 

As much as the distinction of papillary carcinoma versus endocrine thyroid lesions may result in some relevant pitfalls, different immunohistochemical panels have addressed this task. The concept of CD56 deletion has been accepted to be specific for papillary carcinoma. 

Objectives 

This study was an attempt to test CD56 immunoexpression in papillary carcinoma in this locality and to study the relative association of CD56 immunoexpression with BRAFV600 gene mutation on papillary carcinoma.

Methods 

Paraffin embedded, thyroid biopsy specimens containing papillary carcinoma were available for 70 patients. The immunohistochemical technique applied was streptavidin-biotin, using CD56 mouse monoclonal antibodies manufactured by Ventana Corporation (Ventana, Rocklin, Calif). BRAFV600 gene mutation was tested on 48 cases using Real-Time PCR, the target (BRAFV600) DNA was amplified with the mutation-specific primers. 

Results 

Out of 70 papillary carcinoma cases, 7.1% showed CD56 immunopositivity and out of 48 cases, 27.1% were positive for BRAFV600 gene mutation. Morphologically, the five CD56 positive cases included 2 follicular variants, 2 anaplastic and 1 conventional papillary carcinoma. On the other hand, the thirteen BRAFV600 positive cases encompassed 8 conventional, 2 microcarcinoma, 2 columnar variant and 1 anaplastic thyroid carcinoma. The frequency of BRAF mutation was statistically highest among the conventional papillary carcinoma. No any association was detected between CD56 immunostaining and BRAFV600 gene mutations.

Conclusions

Our findings suggest that although CD56 negativity helps but can not role out papillary thyroid canrcer. There is no any association between CD56 expression and BRAF gene mutation at least among our cases.

KEYWORDS

Papillary thyroid carcinoma, BRAF, CD56.

References

1. American Cancer Society. Cancer Facts and Figures 2012. Atlanta, Ga: American Cancer Society, 2012. http://www.cancer.org/acs/groups.

2. Wartofsky L. Increasing world incidence of thyroid cancer: increased detection or higher radiation exposure. 2010 Apr-Jun;9 (2):103-8.

3. Davies L, Ouellette M, Hunter M, Welch HG. The increasing incidence of small thyroid cancers: where are the cases coming from? Laryngoscope. 2010;120(12):2446-51.

4.  Iraqi cancer registry. Results of Iraqi cancer registry 1991-2010. World health organization, Ministry of Health (WHO), Baghdad, lraq. 2012.

5. Othman RT, Abdulljabar R, Saeed A, Kittani SS, Sulaiman HM, Mohammed SA, Rashid RM, Hussein NR. Cancer Incidence Rates in the Kurdistan Region/Iraq from 2007-2009. Asian Pac J Cancer Prev. 2011;12 (5):1261-4.

6. Boila AN, Catana R, Lochin A, Radu G T. Diagnostic value of HBME-1, CD56, Galectin-3 and Cytokeratin-19 in papillary thyroid carcinomas and thyroid tumors of uncertain malignant potential. R J M E. 2014;55(1):49–56.

7. Mokhtari M, Eftekhari M, and Tahririan R. Absent CD56 expression in papillary thyroid carcinoma: A finding of potential diagnostic value in problematic cases of thyroid pathology. 2013;18(12):1046–1050.

8. Park, W. Y., Jeong, S. M., Lee, J. H., Kang, H. J., Sin, D. H., Choi, K. U., Park, D. Y., Huh, G. Y., Sol, M. Y. and Lee, C. H., Diagnostic value of decreased expression of CD56 protein in papillary carcinoma of the thyroid gland. Basic and Applied Pathology. 2009;2: 63–68.

9.  Nikiforova MN, Kimura ET, Gandhi M, Biddinger PW, Knauf JA, Basolo F, et al. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anasplastic or poorly differentiated carcinomas arising from papillary carcinomas.  J ClinEndocrinolMetab. 2003;88:5399-404.

10. Bizzarro T, Martini M, Marrocco C, D’Amato D, Traini E, Lombardi CP, et al. The Role of CD56 in Thyroid Fine Needle Aspiration Cytology: A Pilot Study Performed on Liquid Based Cytology. 2015.

11. El Demellawy D, Nasr AL, Babay S, Alowami S. Diagnostic utility of CD56 immunohistochemistry in papillary carcinoma of the thyroid.Pathol Res Pract. 2009;205(5):303-9.

12. Jeong D, Jeong Y, Park JH, Han SW, Kim SY, Kim YJ, et al. BRAFV600E Mutation Analysis in Papillary Thyroid Carcinomas by Peptide Nucleic Acid Clamp Real-time PCR. Annals of Surgical Oncology. 2013;20(3):759-66.

13. Chien W and Koeffler HP. Molecular Biology of Thyroid Cancer. Endocrine Updates. 2012;30:35-43.

14. Maniatis T, Fritsch EF, Sambrook J. In vitro application of DNA by the Polymerase Chain Reaction, in Molecular Cloning: A Laboratory Manual. 2nd ed. Cold Spring Harbor Laboratory Press. New York, U.S.A. 2001.

15. Pity IS, Salih AM, Hassan N. BRAFV600gene mutation in thyroid cancer in Duhok-Iraq. DMJ. 2015;1: 30-6.

16. George GG, IbrahimHH, ArifSH, Pity IS. Coexpression of HER2 and p53 in gastric and esophageal adenocarcinoma. DMJ. 2015;1:63-76.

17. Pity IS, Jalal AJ. Expression of Ki-67 and p53 in oral squamous epithelial abnormalities. Medical Journal of Babylon. 2013; 10(1):85-99.

18. Pity IS, Baizeed AM. Identification of helicobacter pylori in gastric biopsies of patients with chronic gastritis, histopathological, immunohistochemical study. Duhok Med J. 2011;5(1):69-77.

19. Ciampi R, Knauf JA, Kerler R, Gandhi M, Zhu Z, Nikiforova MN, et al. Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer.  J Clin Invest. 2005;115:94-101

20. Cerrato A, De Falco V, Santoro M. Molecular genetics of medullary thyroid carcinoma: the quest for novel therapeutic targets. Journal of Molecular Endocrinology (2009) 43, 143–155.

21. Goutas N, Vlachodimitropoulosi D, Bouka M, Lazaris AC, Nasioulas G, Gazouli M. BRAF and K-RAS Mutation in a Greek Papillary and Medullary Thyroid Carcinoma Cohort. Anticancer research. 2008;28: 305-8.

22. Xing M. BRAF mutation in thyroid cancer. Endocrine-Related Cancer, 2005;12:245–62.

23. Chen JH, Faquin WC, Lloyd RV, Nose V. Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma.  Mod Pathol.  2011;24(5):739-49. 

24.  Rosai J. Thyroid gland in: Rosai and Ackerman’s Surgical Pathology. 10th ed. St Louis: Mosby. 2010;488-538.

25. Lin JD, Kuo SF, Chao TC, Hsueh C. Incidental and nonincidental papillary thyroid microcarcinoma. Ann SurgOncol. 2008; 15:2287-92.

26. Xing M. Prognostic utility of BRAF mutation in papillary thyroid cancer. Molecular and Cellular Endocrinology 321. 2010;86–93.

27. Tang KT, Lee CH. BRAF Mutation in Papillary Thyroid Carcinoma: Pathogenic Role and Clinical Implications. J Chin Med Assoc.  2010;73(3):113–28.

28. Roti E, Uberti EC, Bondanelli M, Braverman LE. Thyroid papillary microcarcinoma. A Descriptive and Meta-Analysis Study. Eur J Endocrinol. 2008;159(6):659-73.

29. Flanagan MB, Li-Volsi VA, Baloch ZB: Long term follow-up of patients with follicular variant of papillary thyroid carcinoma (FVPTC).  Lab Invest. 2009; 89(1):247-11.

30. Kondo T, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer. 2006;6:292-306.

31. Adeniran AJ, Zhu Z, Gandhi M, Steward DL, Fidler JP, Giordano TJ, et al. Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas.  Am J Surg Pathol. 2006;30:216-22.

32. Giordano TJ, Kuick R, Thomas DG, Misek DE, Vinco M, Sanders D, et al. Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis.  Oncogene. 2005;24:6646-6656. 

33. Abdelzaher E, RizkAM, Allam M. A Logistic Regression Model Predicting Malignancy in Follicular Thyroid Lesions Based on CD56 Expression and Patient’s Age. Journal of Interdisciplinary Histopathology. 2014; 2 (4):205-12.

34. El Demellawy D, Nasr A, Alowami S: Application of CD56, P63 and CK19 immunnohistochemistry in the diagnosis of papillary carcinoma of thyroid. Diagnostic Pathology 2008, 3:5.

35. Tallini G. Poorly differentiated thyroid carcinoma. Are we there yet? EndocrPathol. 2011;22(4):190-4.

36. Giusti F, Falchetti A, Franceschelli F, Marini F, Tanini A, Luisa Brandi M. Thyroid cancer: current molecular perspectives. J Oncol. 2010;2010.

Full Text

 © The Authors, published by University of Sulaimani, College of Medicine

This work is licensed under a Creative Commons Attribution 4.0 International License.