Genetic instabilities of chromosome 9, 17 and accumulation of p53 overexpression during multistage tumorigesis in head and neck cancer.
Malignant transformation and tumor progression are currently thought to be the result of the accumulation of genetic alterations in critical genes, the proto-oncogenes and the tumor suppressor genes. Among the tumor suppressor genes, the p53 tumor suppressor gene mutations are the most prevalent. In order to determine genetic instability and p53 expression, we analyzed the genetic changes of chromosome 9 and 17 by non-isotopic in situ hybridization in formalin-fixed, paraffin embedded tissues and calculated for normalized chromosome index (NCI) and polysomy index (PI), and the expression of p53 by using immunohistochemistry (IHC). The means of chromosome 9 and 17 NCI were found to increase gradually as the tissues progressed from normal to squamous cell carcinoma; 1.02 and 1.03, respectively, in normal adjacent tissue (ANL), 1.19 and 1.20 in hyperplasia (HYP), 1.28 and 1.31 in mild dysplasia (MD), 1.38 and 1.43 in moderate dysplasia (ModD), 1.39 and 1.66 in severe dysplasia/carcinoma in situ (SD/CIS), and 1.65 and 1.83 in squamous cell carcinoma (SCC). Moreover, the PI 9 and 17 means also increased as the tissues passed from histologically normal epithelium to HYP to dysplasia (DYP) to cancer. In ANL, PI 9 and 17 means were 0.90 and 1.53 percent, compared to 3.78 and 3.38 percent in HYP, 3.73 and 5.12 percent in MD, 5.66 and 8.47 percent in ModD, 13.56 and 20.99 percent in SD/CIS, and 17.74 and 22.50 percent in SCC. Interestingly, p53 expression also increased continuously, not only in amount but also in the incidence of its expression, as the tissues progressed from normal to cancer, 2.29 percent in ANL, 4.65 percent in HYP, 9.09 per cent in MD, 9.58 per cent in ModD, 29 percent in SD/CIS, and 38.67 per cent in SCC in the amount; and 3 of 33 (9%) in ANL, 6 of 37 (16%) in HYP, 5 of 21 (24%) in MD, 3 of 12 (25%) in ModD, 8 of 18 (44%) in SD/CIS, and 24 of 49 (49%) in SCC in the incidence. Our studies demonstrated that genetic instability and p35 expression occurred very early from ANL to SCC and increased gradually through HYP, DYP, to SCC in head and neck cancer. The genetic instability and the loss of normal p53 function play the potential role in multistep tumorigenesis in head and neck cancer and might be the useful biomarkers in assessing the risk of tumor development.
Charuruks
N
N
Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Shin
D M
DM
Voravud
N
N
Ro
J Y
JY
Hong
W K
WK
Hittelman
W N
WN
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D015870:Gene Expression; D016158:Genes, p53 / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D009154:Mutation / Q000235:genetics; D016612:Paraffin Embedding