Immunohistochemical study of DNA topoisomerase I, DNA topoisomerase II alpha, p53, and Ki-67 in oral preneoplastic lesions and oral squamous cell carcinomas.
Human DNA topoisomerase I (topo I) is the molecular target of the camptothecin group of anticancer drugs. Laboratory studies have shown that the cellular response to topo I-targeted drugs depends on the topo I expression and DNA replication rate and the apoptotic pathway activity. In this study, we tested potential indicators of the sensitivity of topo I-targeted drugs in 36 cases of oral squamous cell carcinoma (OSCC). Formalin-fixed, paraffin-embedded tissue sections were immunostained with monoclonal antibodies against Ki-67, p53, and topo I, and with polyclonal antibodies against DNA topoisomerase II-alpha (topo II-alpha). These markers were also tested in 18 epithelial hyperplastic lesions and 18 mild dysplasias. Immunostaining was quantified by the percentage of stained nuclei in each sample (the labeling index); 200 immunoreactive epithelial nuclei were counted per case for each antibody. The results support the possibility of using topo II-alpha staining for assessing the proliferative activity. High expression of topo II-alpha and topo I in OSCCs suggests that they may serve as potential indicators of sensitivity to topo I inhibitors. However, the apoptotic pathway assessed by p53 immunostaining was found to be uninformative. Analysis of the relationship between immunohistochemical results and clinical and pathologic parameters (the T and N stages and differentiation) showed that only the differentiation parameter correlated with the topo I expression rate. Thus, significant increase in the topo I expression in the poorly differentiated OSCCs suggests their higher sensitivity to drug treatment.
Hafian
Hilal
H
Service d'Odontologie, Département de Chirurgie et Pathologie Orale, EA no. 3306 ICMC, and Laboratoire d'Anatomie et Cytologie Pathologiques, CHU de Reims, Reims, France.
Venteo
Lydie
L
Sukhanova
Alyona
A
Nabiev
Igor
I
Lefevre
Benoît
B
Pluot
Michel
M
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D004264:DNA Topoisomerases, Type I / Q000096:biosynthesis*; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II