Proliferative index

Proliferation, as one of the hallmarks and most fundamental biological processes in tumors, is associated with tumor progression, response to therapy, and cancer patient survival. Consequently, the evaluation of a tumor proliferative index (or growth fraction) has clinical significance in characterizing many solid tumors and hematologic malignancies. This has led investigators to develop different technologies to evaluate the proliferation index in tumor samples. The most commonly used methods in evaluating a proliferative index include mitotic indexing, thymidine-labeling index, bromodeoxyuridine assay, the determination of fraction of cells in various phases of cell cycle, and the immunohistochemical evaluation of cell cycle-associated proteins. Proliferation, as one of the hallmarks and most fundamental biological processes in tumors, is associated with tumor progression, response to therapy, and cancer patient survival. Consequently, the evaluation of a tumor proliferative index (or growth fraction) has clinical significance in characterizing many solid tumors and hematologic malignancies. This has led investigators to develop different technologies to evaluate the proliferation index in tumor samples. The most commonly used methods in evaluating a proliferative index include mitotic indexing, thymidine-labeling index, bromodeoxyuridine assay, the determination of fraction of cells in various phases of cell cycle, and the immunohistochemical evaluation of cell cycle-associated proteins. Mitotic indexing is the oldest method of assessing proliferation and is determined by counting the number of mitotic figures (cells undergoing mitosis) through a light microscope on H&E stained sections. It is usually expressed as the number of cells per microscopic field. Cells in the mitotic phase are identified by the typical appearance of their chromosomes in the cell during the mitotic phase of the cell cycle. Usually the number of mitotic figures is expressed as the total number in a defined number of high power fields, such as 10 mitoses in 10 high power fields. Since the field of vision area can vary considerably between different microscopes, the exact area of the high power fields should be defined in order to compare results from different studies. Accordingly, one of the main problems of counting mitosis has been the reproducibility. Thus, the need for standardized methodology and strict protocols is important to achieve reproducible results. Thymidine-labeling indexing is determined by counting the number of tumor nuclei labeled on autoradiographed sections after incubating the tumor cells with thymidine. Rapidly proliferating cells readily update more radiolabeled Thymidine, which produces darker spots on the autoradiograph film.