Prediction of human oral cancer radiation responsiveness by histone (H3) mRNA in situ hybridization: a preliminary report.
OBJECTIVE
Cell cycle kinetics are believed to be a key determinant in radiation responsiveness. However, histomorphologic analysis remains an unreliable method of identifying proliferating cells. In this study, the fraction of cells undergoing division within oral cancer biopsy samples was used to predict the responsiveness of the tumor to radiation therapy.


METHODS
Eighteen cases of T1 or T2 squamous cell carcinoma of the floor of the mouth with known clinical outcomes were identified. All were treated at the Massachusetts General Hospital with external beam radiation therapy alone. The fraction of proliferating cells was determined using in situ hybridization of histone (H3) mRNA expression. Tissue viability and mRNA status was verified using in situ hybridization for beta-actin mRNA expression.


RESULTS
Matching the fraction of oral tumor cells positively labeled for histone (H3) mRNA (histone labeling index or HLI) with the actual clinical outcome showed that the HLI of radioresponsive oral tumors (12 cases) was 0.336+/-0.185 (approximately 34%+/-19%), whereas that for radioresistant oral tumors (six cases) was 0.088+/-0.078 (approximately 9%+/-7.8%). Using t-test statistical analysis for unpaired samples showed that the difference in HLI between the two 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 for human oral cancer.
Donoff
R B
RB
Department of Oral and Maxillofacial Surgery, Harvard School of Dental Medicine, Massachusetts General Hospital, Boston, USA.
Todd
R
R
Elovic
A
A
Gallagher
G T
GT
Chou
M Y
MY
Wong
D T
DT
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy*; D002455:Cell Division / Q000528:radiation effects; D016371:Cranial Irradiation / Q000706:statistics & numerical data; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy*; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis; D011836:Radiation Tolerance / Q000235:genetics*; D016196:S Phase / Q000528:radiation effects; D014067:Tonsillar Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy
D006657:Histones; D015347:RNA Probes; D012333:RNA, Messenger