| The tumors, which have no obvious difference with benign and malignant diseases, or just develop from benign phase to malignant phase, are called borderline tumors. According to the different understanding of these diseases, it is very difficult to diagnose such patients exactly. There are huge bifurcation about distinguishment between benign and malignant thyroid diseases, such as multinodular goiter complicated with atypical hyperplasia, atypical adenoma, Hurthle cell adenoma, and Hashimoto's thyroiditis. For investigation of borderline thyroid tumors, we used Flow cytometry to research DNA content and the relationship between cell cycle and atypical hyperplasia of multinodular goiter, immunohistochemical to examine the expression of CK-19 and Galectin-3 in papillary adenoma, Hashimoto's thyroiditis, and multinodular goiter, and RT-PCR to detect the relationship between RET/PTC rearrangement and carcinomatous change.In our data, the cellular DNA index and heteroploid frequency of multinodular goiter patients with atypical hyperplasia distinctly increased. Simultaneously, the ratio of S phase and proliferation index (PI) of such patients, which were lower than those of papillary thyroid carcinoma, were higher than those of control group and goiter patients without atypical hyperplasia. It indicated that multinodular goiter with atypical hyperplasia, which had the potential of malignant transformation, was at the proliferative status between benign hyperplasia and carcinoma. Furthermore, if the volume of PI is beyond 15, we should pay much attention to carcinomatous change of such diseases.All papillary carcinomas in our experiment demonstrated strong immunoreactivity for CK-19. In most of papillary adenoma, nodular goiter and Hashimoto's thyroiditis, it was focal from weak to moderate. Otherwise, the immunoreactivity to CK-19 in Hurthle cell adenoma was from moderate to strong. Observation of benign cases with strong immunoreactivity through H-E stained slice, we found it is difficult to distinguish from malignant cases; thus, such cases should be included in borderline group. According to our data, the sensitivity of CK-19 as the criterion for the diagnosis of thyroid carcinoma was 100 percent, and the specificity of it was 53 percent. Another important immunohistochemical marker of thyroid tumors is Galectin-3, which has high expression frequency in papillary thyroid carcinoma. We used the same method to detect Galectin, and drove the same conclusion, otherwise, the sensitivity of that protein was 96 percent, and the specificity was 89 percent. Therefore, Galectin-3 is more important for difference diagnosis of benign and malignant thyroid lesion.Thyroid papillary carcinomas are characterized by RET/PTC rearrangements that result in fusion of the tyrosine kinase domain of the RET receptor to the N-terminal sequences encoded by heterologous genes. This thyroid specific rearrangement causes aberrant expression of RET/PTC and results in constitutive ligand-independent activation of RET kinase. In our experiment, we designed to investigate the expression of RET/PTC in patients with thyroid tumors by immunohistochemistry, to search specifically for RET/PTC1~3 rearrangements using RT-PCR, and to compare results obtained by immunohistochemistry with those obtained by RT-PCR. Then five of seven cases of positive staining, characterized by papillary carcinoma-type nuclear changes, obtained RET/PTC mRNA. On the contrary, positive staining without evidence of morphological changes obtained no corresponding mRNA. Therefore, gene rearrangement happened earlier than morphological changes in thyroid papillary carcinomas, which could explain the mechanism of malignant transformation of thyroid borderline tumors, and provide us with a reference criterion of surgical treatment.All in all, benign thyroid tumors with negative staining for CK-19 is at benign proliferating phase, and those with CK-19 expression is at active proliferating phase; coexpression of CK-19 and Galectin-3 indicates the patients...
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