P53 expression and polysomies of chromosome 9, 17 in head and neck cancer prognosis.

Sixty-nine cases of head and neck squamous cell carcinoma were examined by immunohistochemistry for p53 and chromosome in situ hybridization for chromosome 9 and 17 to determine the relationship between p53 expression and polysomies of chromosome 9 and 17 with the development of a second primary tumor as well as recurrence of primary tumor of head and neck squamous cell carcinoma. We found early expression of p53 in the normal and premaligant lesions adjacent to tumor which was associated with a gradual increase in the fraction of positive nuclei as well as numbers of cancer. We also found statistically significant increments of polysomies of chromosome 9 and 17 in terms of the polysomy index seen through the histologic changes occurring during multistep tumorigenesis. Our results could not demonstrate statistically significant correlation between p53 expression and PI 9 and 17 in tumorigenesis. Interestingly, however, there was a strong correlation between p53 expression and second primary tumor as well as recurrence of primary tumor. The p53 expressed group had a seven fold increased incidence in developing second primary tumor and a two and a half times increased incidence for recurrence of primary tumor, compared to the non-expressed group. We conclude that p53 expression and polysomies of chromosome 9 and 17 have an important role in multistep tumorigenesis in HNSCC. There was no significant correlation between p53 expression and polysomies of chromosome 9 and 17. However, the expression of p53 was statistically significant for association with second primary tumor and recurrence of primary tumor of head and neck squamous cell carcinoma.

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.

Genetic instability and the development of recurrence of primary tumor and second primary tumor during head and neck tumorigenesis.

To determine whether the degree of genetic instability is associated with the development of recurrence of primary tumor (RPT) and second primary tumor (SPT), we examined 46 cases of head and neck squamous cell carcinomas (HNSCC) by nonisotopic in situ hybridization using chromosome specific DNA probes for chromosome 9 and 17. Forty-six cases were classified into three groups; group I, 15 cases without developing RPT and SPT; group II, 21 cases with RPT, and group III, 10 cases with SPT. We demonstrated the statistical significant increment of genetic instability in terms of normalized chromosome index (NCI) and polysomy index (PI) of chromosome 9 and 17 from normal adjacent to malignant lesions (ANL), to hyperplasia (HYP), to dysplasia (DYP), to squamous cell carcinomas (SCC). Our results demonstrated the trend of increased chromosome indices as the tissue progressed from ANL to SCC in group II over group I. However, when we compared the genetic instability between group I and the specimens from the patients who developed RPT within 6 months (group III), we found the significant increment of PI of both chromosome 9 (0.84 +/- 0.54 vs 1.25 +/- 0.46, p = 0.10) and 17 (1.02 +/- 0.62 vs 1.89 +/- 0.87, p = 0.06) on ANL in the later group. Our results also demonstrated the higher trend of genetic instability on ANL in group III over group I as shown by the statistical significance of NCI of both chromosome 9 (0.98 +/- 0.12 vs 1.06 +/- 0.02, p = 0.05) and 17 (1.02 +/- 0.09 vs 1.10 +/- 0.05, p = 0.05). These results suggested that the degree of genetic instability might be used as a potential molecular marker for the risk assessment of early RPT and SPT development during head and neck tumorigenesis.