Differential Diagnosis On Benign And Malignant Thyroid Follicular Hyperplastic Nodule

Objective: In order to provide marker of diagnosis and differentiated diagnosis of benign and malignant thyroid follicular hyperplastic nodules, the expression of DDIT3 mRNA and DDIT3 protein, Galectin-3, CK19 and Ki-67 protein was detected in benign and malignant thyroid follicular hyperplastic nodules.Methods: 99 cases of paraffin-embedded tissue of thyroid follicular hyperplastic nodules were collected from archives of Department of Pathology in Shihezi University School of Medicine and People's Hospital of Xinjiang Uygur Autonomous Region from 1983 to 2007, including 46 cases of follicular carcinoma (FTC), 14 cases of follicular variant of papillary carcinoma (FVPTC), 25 cases of follicular adenoma (FTA) and 14 cases of adenomatous goiter. 23 cases of surgery fresh specimens of thyroid nodules were collected from December 2006 to November 2007, including 4 cases of papillary carcinoma, 2 cases of FTC, 8 cases of FTA and 9 cases of nodular goiter. All cases were stained by HE staining and diagnosed by two senior pathological professors referring to the 2004 WHO classification standards. The expression of DDIT3, Galectin-3, CK19 and Ki-67 protein was detected in benign and malignant thyroid follicular hyperplastic nodules by immunohistochemical staining and the expression of DDIT3 gene mRNA was detected in 40 cases of benign and malignant thyroid nodules by reverse transcriptase polymerase chain reaction (RT-PCR). All dates were analysis by software SPSS13.0 and combining with clinical and pathological data to analysis it.Results: The positive rates of DDIT3, Galectin-3 and CK19 protein expression in benign and malignant thyroid follicular hyperplastic nodule were 23.1%, 10.1%, 23.1% and 91.7%, 76.7%, 60%, respectively. There was a significant difference of the three markers expression between benign and malignant group (P < 0.001). While Galectin-3 and CK19 protein expression was significant difference between FVPTC and FTC group (P < 0.01). The expression indexes of Ki-67 in benign and malignant group were 2.49±1.98 and 8.98±9.24, respectively and there was also a significant difference between benign and malignant group (P < 0.001). DDIT3 mRNA expression of 40 cases of thyroid nodules by RT-PCR showed that DDIT3 mRNA expression in 9 cases of nodular goiter, 8 cases of FTA, 23 cases of thyroid carcinoma was 0.13±0.19, 0.55±0.35 and 1.05±0.36, respectively, but five cases of adjacent thyroid carcinoma tissues had negative expression of DDIT3 mRNA.Conclusion: (1) DDIT3, Galectin-3, CK19 and Ki-67 protein expression was helpful for the diagnosis and differential diagnosis of thyroid carcinoma based on the morphological characteristics. (2) The expression of Galectin-3 and CK19 protein had high sensitivity for diagnosis of FVPTC. If the expression of Galectin-3 was positive in benign lesions, we regarded it as a potential higher-risk of malignant lesions and it is needed to further study by clinical follow-up. (3) DDIT3 mRNA expression in thyroid carcinoma had noticeably increased. It can be used as molecular target in early diagnosis of thyroid cancer. Whether it will participate in the development of thyroid carcinoma or not, we should further study with more cases.