Evaluation of CCND2, PLAB, PCSK2 and FHL1 Genes Expression Efficiency to Differentiate between Papillary Thyroid Carcinoma and Benign Tumors

Document Type : Original Article


1 Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Noor Medical Genetics Laboratory, Ahvaz, Iran.

3 -Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

4 Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 3-Noor Medical Genetics Laboratory, Ahvaz, Iran.


the best method for sample collection in diagnosis of thyroid tumors before surgery which is performed widely for patients, but unfortunately for about 20% of cases, the test result is reported as suspicious or intermediate. Also, due to false positive and negative responses, there is a pressing need for a biomarker to improve the accuracy of preoperative tests. The aim of this study was to evaluate the relative mRNA expression of genes CCND2, PLAB, PCSK2 and FHL1 in differentiating benign and malignant tumors of papillary thyroid carcinoma.
Subjects and Methods: Fifty samples from patients with malignant thyroid tumors (25 cases) and benign thyroid tumors (25 cases) were enrolled in this study, RNA was extracted from paraffin samples with High Pure RNA Paraffin Kit and RNA extracted was used for cDNA synthesis. Real Time PCR reactions were performed in duplicate consists of 20 ml of the reaction mixture containing the fluorescent cyber ​​green.
Results: The relative mRNA expression of CCND2, PLAB and PCSK2 genes were not efficient for diagnosis. However, the relative mRNA expression of FHL1 gene could differentiate 21 malignant cases with 4 false positive results.
Conclusions:The relative mRNA expression of FHL1 gene is more efficient to differentiate papillary thyroid carcinoma from benign tumors.


Xing MHaugen BRSchlumberger M. Progress in molecular-based management of differentiated

    thyroid cancer. Lancet 2013 Mar; 23: 1058-69.

2-Schagdarsurengin U O, Gimm H, Dralle C, Hoang-Vu, Dammann R. CpG island methylation of tumor-related promoters occurs preferentially in undifferentiated carcinoma. Thyroid 2006;16: 633-42.
3-Weber F, Shen L, Aldred MA, Morrison CD, Frilling A, Saji M, ‘et al’. Genetic classification of benign and malignant thyroid follicular neoplasia based on a three-gene combination. J Clin Endocrinol Metab 2005; 90: 2512-21.
4-Lee JH, Lee ES, Kim YS. Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid: a meta-analysis. Cancer 2007;110: 38-46.
5-Shibru D J, Hwang E, Khanafshar QY, Duh OH, Clark, Kebebew E. Does the 3-gene diagnostic assay accurately distinguish benign from malignant thyroid neoplasms?. Cancer 2008; 113: 930-5.
6-Kebebew E, Peng M, Reiff E, Duh QY, Clark OH, McMillan A. Diagnostic and prognostic value of angiogenesis-modulating genes in malignant thyroid neoplasms. Surgery 2005; 138: 1102-9.
7-Hoque MO, Rosenbaum E, Westra WH, Xing M, Ladenson P, Zeiger MA,’et a’l. Quantitative assessment of promoter methylation profiles in thyroid neoplasms. J Clin Endocrinol Metab 2005; 90: 4011-8.
8-Chung KW, Yang SK, Lee GK, Kim EY, Kwon S, Lee SH, ‘et al’. Detection of BRAFV600E mutation on fine needle aspiration specimens of thyroid nodule refines cyto-pathology diagnosis, especially in BRAF600E mutation-prevalent area. Clin Endocrinol (Oxf) 2006; 65: 660-6.
9-Rowe LRM, Bentz BGM, Bentz JSM. Utility of BRAF V600E mutation detection in cytologically indeterminate thyroid nodules. Cytojournal 2006; 3: 10.
10-Asa SL. The role of immunohistochemical markers in the diagnosis of follicular-patterned lesions of the thyroid. Endocr Pathol 2005; 16:  295-309.
11-Cerutti JM, Delcelo R, Amadei MJ, Nakabashi C, Maciel RM, Peterson B, ‘et al’. A preoperative diagnostic test that distinguishes benign from malignant thyroid carcinoma based on gene expression. J Clin Invest 2004; 113: 1234-42.
12-Nikiforova M, Durso MB, Kelly LM, Nikiforov YE. Testing for 740 Mutations in Thyroid Samples Using Targeted Next Generation Sequencing Approach. In: 82nd Annual Meeting of the American Thyroid Association; 2012 Sep 19-23 ; Quebec, Canada; 2012. p. A-79.
13-Song Q, Wang D, Lou Y, Li C, Fang C, He X, ‘et  al’.  Diagnostic  significance  of  CK19,  TG, Ki67  and  galectin-3  expression  for  papillary thyroid carcinoma in the northeastern region of China. Diagn Pathol 2011; 6: 126.
14-Xing M. Recent advances in molecular biology of thyroid cancer and their clinical implications. Otolaryngol Clin North Am 2008; 41: 1135-46.
15-Fryknas M, Wickenberg-Bolin U, Goransson H, Gustafsson MG, Foukakis T, Lee JJ, ‘et al’. Molecular markers for discrimination of benign and malignant follicular thyroid tumors. Tumour Biol 2006; 27: 211-20.
16-Li X, Jia Z, Shen Y, Ichikawa H, Jarvik J, Nagele RG, ‘et al’. Coordinate suppression of Sdpr and Fhl1 expression in tumors of the breast, kidney, and prostate. Cancer Sci  2008; 99: 1326-33.
17-Sakashita K, Mimori K, Tanaka F, Kamohara Y, Inoue H, Sawada T, ‘et al’. Clinical significance of loss of Fhl1 expression in human gastric cancer. Ann Surg Oncol 2008; 15: 2293-300.
18-Mohammadi-Asl  J,  Dinarvand  GhA,  Golchin  N,  Saki  N,  Ranjberi  N,  Rashidi  I.  The  Diagnostic Value of Gene Expression of FHL1 in the Differential Diagnosis of Papillary Thyroid Carcinoma and Benign Tumors. J Isfahan Med Sch 2014; 31(266): 1-9.