Research Of The Expression Of Mcm5, Cdc6 And Ki67 In Thyroid Tumors

[ Objective] Thyroid tumors are the most common endocrine tumors. There are many pathological categories of thyroid tumors and their biological behaviors are different from each other, which made it difficult to tell malignant thyroid tumors from benign tumors just by morphology. Therefore, there are hot researches in searching for molecular markers of thyroid carcinomas for pathological diagnosis in recent years.Minichromosome maintenance protein 5 (Mcm5) and cell division cycle protein 6(Cdc6) are important regulators in the process of eukaryotic DNA replication. They are both elements of DNA prereplicative complexes (Pre-Rcs).Mcm5 which is one part of Mcm family proteins, along with other five highly homologous Mcm proteins forms a ring soluble double trimeric complex with DNA helicase activity. The function of Mcm5 protein lies on the conserved ATPase motif in its central domains. The functional Mcm protein complexes are not only essential for initiation of DNA replication but also required for elongation stage of replication fork. Mcm5 protein is associated with RNA II polymerase and can enhance the progression of transcription.Cdc6 is a member of the large superfamily of ATPases. Cdc6 associated with Cdc10 dependent transcript 1 ( Cdt 1 ) might have a function as an ATP-dependent Mcm protein complexes loader in G1 phase of DNA replication. Being an enzyme of energy metabolism of DNA replication during the cell cycle, Cdc6 protein has the function of enhancing ATP combination and ATP hydrolysis.In normal cells, Mcm5 and Cdc6 proteins are present only once during cell cycle and are lost from the cell during quiescence and differentiation states. Not surprisingly then, increased expressions of Mcm5 and Cdc6 are seen in dysplastic cells and many tumors. As a consequence, Mcm5 and Cdc6 can be specific biomarkers of proliferating cells. But there are rare reports about their effects on thyroid tumors. By measuring the expressions of Mcm5 and Cdc6 in thyroid tumor tissues and comparing them with Ki67, we try to explore the significance of these two proteins in the development and diagnosis of thyroid cacinomas.[Methods] The expressions of Mcm5, Cdc6 and Ki67 in 15 cases of thyroid adenoma and 49 cases of thyroid carcinoma are detected by S-P immunohistochemical technique. 49 cases of thyroid carcinoma consist of 20 cases of papillary carcinoma, 13 cases of follicular carcinoma, 9 cases of medullary carcinoma and 7 cases of undifferentiated carcinoma.[Results] Mcm5 shows nuclear staining in undifferentiated carcinoma, medullary carcinoma and papillary carcinoma. Label index of them are 29.14 ± 12.32,10.11 ± 6.51,2.60 ± 2.11, respectively. Mcm5 shows negative expression in follicular carcinoma and thyroid adenoma. The expression of Mcm5 is significant different between undifferentiated carcinoma, medullary carcinoma, papillary carcinoma and thyroid adenoma (P <0.05).Undifferentiated carcinoma, medullary carcinoma and papillary carcinoma also display nuclear staining with anti-Cdc6. Label index of them are 14.71± 9.47,5.33 ±4.90,1.55 ± 1.47, respectively. Follicular carcinoma and thyroid adenoma are negative expression. There is significant difference in the expression of Cdc6 between undifferentiated carcinoma, medullary carcinoma, papillary carcinoma and thyroid adenoma(P <0.05).Ki67 both has positive nuclear staining in undifferentiated carcinoma, medullary carcinoma, papillary carcinoma and also in follicular carcinoma, thyroid adenoma. Label index of them are 31.74 ± 13.31,12.11 ± 5.49,3.25 ± 2.72,5.23 ± 2.72,1.07 ± 2.09, respectively.The expression of Ki67 has significant difference between undifferentiated carcinoma, medullary carcinoma, papillary carcinoma, follicular carcinoma and thyroid adenoma (P<0.05).The expressions of Mcm5, Cdc6 and Ki67 are positive related with each other in thyroid carcinoma.The expressions of Mcm5, Cdc6 and Ki67 don't have significant difference between groups of lymph nodes metastasis and groups without lymph nodes metastasis(P>0.05).[Conclusions] Mcm5 and Cdc6 can reflect the degree of cellular proliferating activity of thyroid carcinomas and might be regarded as referenced parameters in helping diagnosing undifferentiated carcinoma, medullary carcinoma and papillary carcinoma; Combing immunohistoche-mical detection of Mcm5, Cdc6 and Ki67 can help to distinguish undifferentiated carcinoma, medullary carcinoma and papillary carcinoma from thyroid adenoma; The expressions of Mcm5, Cdc6 and Ki67 proteins are not related to patients'lymph nodes metastasis.