PCNA expression as a marker of proliferation in benign and highly differentiated malignant tumors of the human thyroid gland (literature review and clinical case)

摘要

Determining of the proliferative potential of tumor cells is an important task for the diagnosis of thyroid cancer. Therefore, a search for markers characterizing the state of proliferative processes is necessary. Proliferating cell nuclear antigen (PCNA), a protein necessary for the organization of components involved in DNA replication and repair, along with Ki-67 is one of the main markers of proliferative processes. Recent studies have shown its ability to interact with many factors that are involved in several metabolic pathways, including DNA repair, translesion DNA synthesis, DNA methylation, chromatin remodeling and cell cycle regulation. The review presents the data on its structure, function, regulation and involvement in malignant transformation of cells. To determine biomar­kers useful for thyroid cancer diagnosis and installing a panel of markers for the early detection of metastatic carcinomas of the thyroid gland, a number of studies have been conducted, which showed that PCNA levels are almost 2-fold higher in metasta­tic than in non-metastatic tumors. An increased expression of PCNA in thyroid carcinomas was also noted as compared with adenomas. The highest level of PCNA expression was observed in the most aggressive types of thyroid cancer — anaplastic and medullary carcinomas. In differentiated tumors, the amount of antigen was somewhat lower, but it increased markedly in invasive variants of these tumors. PCNA expression was enhanced in B-RAF V600E-positive papillary carcinomas compared with B-RAF V600E-negative. A patient survival analysis that was associated with PCNA and Ki-67 marker levels showed a better prognosis in patients with low PCNA levels. The worse results were observed in patients with moderate PCNA, and the worst prognosis was for patients with high antigen values. The possibilities of suppressing PCNA with specific inhibitors for the treatment of certain types of cancer are discussed.