A possible evaluation system for effect of oral cancer chemotherapy based on the grading of apoptotic changes in the carcinoma cells

2000 Fiscal Year Final Research Report Summary

• Project/Area Number: 11671975
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Tohoku University
• Principal Investigator: MORIKAWA Hidehiro Graduate School of Dentistry, Tohoku University Assistant Professor, 大学院・歯学研究科, 助手 (60302155)
• Co-Investigator(Kenkyū-buntansha): MORI Shiro Dental Hospital, Tohoku University Lecturer, 歯学部・附属病院, 講師 (80230069)
• Project Period (FY): 1999 – 2000
• Keywords: oral squamous cell carcinoma / cancer chemotherapy / anti-cancer agent / pathological effect / apoptosis / apoptosis-related markers / metastasis / survival rate

Research Abstract

To test whether grading of apoptotic changes of carcinoma cells in the course of chemotherapy for oral squamous cell carcinoma (SCC) can be useful in evaluation of the effect of the therapy, we examined the apoptotic carcinoma cells in tissue sections prepared from specimens obtained before and after the chemotherapy. Apoptotic cells in the fresh frozen tissue sections were detected by terminal deoxynucleotidyl transferase (TdT)-biotin end-labeling (TUNEL) method. Although detection of apoptotic cells in the SCC by the TUNEL method might be useful as a tool to evaluate the effect of the cancer chemotherapy, examination of apoptotic cells by only the TUNEL method was not enough for the evaluation system for the effect of chemotherapy. The TUNEL methods, moreover, is complex and expensive to perform because of the complicated processes involved and the use of the expensive reagents. As an another method to detect apoptotic cells in situ, the immunohistochemical detection of single-strand ed (ss) DNA has demonstrated to be great value of identification of cells which undergo apoptosis or programmed cell death. To examine reliability of the assay by means of the immunohistochemistry, we comparatively investigated the extent of apoptotic cell loss in SCCs evaluated by two methods, namely the TUNEL method and immunohistochemistry for ssDNA.As a result, a significant correlation in the apoptotic indexes evaluated by these methods was found. However an evaluation system by only detection of apoptotic cells in SCC were still not enough even if immunohistochemistry for ssDNA was successfully performed. Thus we also investigated additional cell marker of SCC cells in which expression might be influenced by cancer chemotherapy. As a result, it was suggested that comparative test concerning the immunohistochemical detection of E-cadherin, α catenin, heparansulfate glycosaminoglycan, Cyclin D1, and Ki67 in the SCC specimens obtained before and after the chemotherapy might be a candidate evaluation system for the effect of the cancer chemotherapy.