Prediction of human oral cancer radiation responsiveness by histone (H3) mRNA in situ hybridization: A preliminary report

Purpose: Cell cycle kinetics are believed to be a key determinant in radiat ion responsiveness; However, histomorphologic analysis remains an unreliabl e method of identifying proliferating cells. In this study, the fraction of cells undergoing division within oral cancer biopsy samples was used to pr edict the responsiveness of the tumor to radiation therapy. Patients and Methods: Eighteen cases of T1 or T2 squamous cell carcinoma of the floor of the mouth with known clinical outcomes were identified. All w ere treated at the Massachusetts General Hospital with external beam radiat ion therapy alone. The fraction of proliferating cells was determined using in situ hybridization of histone (H3) mRNA expression. Tissue viability an d mRNA status was verified using in situ hybridization for beta-actin mRNA expression. Results: Matching the fraction of oral tumor cells positively labeled for h istone (H3) mRNA (histone labeling index or HLI) with the actual clinical o utcome showed that the HLI of radioresponsive oral tumors (12 cases) was 0. 336 +/- 0.185 (-34% +/- 19%), whereas that for radioresistant oral tumors ( six cases) was 0.088 +/- 0.078 (-9% +/- 7.8%). Using t-test statistical ana lysis for unpaired simples showed that the difference in HLI between the tw o groups was significantly different (P = .0068). Conclusions: It is concluded that the use of in situ detection of histone ( H3) mRNA may be a useful adjunctive criterion in the choice of treatment fo r human oral cancer.