TY - JOUR
T1 - Early genetic changes during upper aerodigestive tract tumorigenesis
AU - Hittelman, Walter N.
AU - Voravud, Narin
AU - Shin, Dong M.
AU - Lee, Jin Soo
AU - Ro, Jae Y.
AU - Hong, Waun Ki
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1993
Y1 - 1993
N2 - Upper aerodigestive tract tumorigenesis has been hypothesized to represent a field cancerization process with multistep events based on its association with known carcinogens, its frequent associated premalignant lesions, and its multifocal clinical manifestation. To further explore this working hypothesis, we have examined normal tissue and premalignant lesions in the field of tumors for evidence of genetic change. Paraffin sections of head and neck tumors harboring neighboring premalignant lesions were explored for the presence of chromosome polysomies using in situ hybridization and chromosome-specific centromeric probes. Cells exhibiting random polysomy were observed in the premalignant regions near the tumors. The frequency of polysomy in the tumor field increased as the tissue progressed from normal morphology (33%), to hyperplasia (67%), to dysplasia (95%), and to squamous cell carcinoma (96%). These results support the notions of field cancerization and multistep tumorigenesis in the aerodigestive tract. To determine whether the degree of accumulated genetic alterations might serve as a biomarker for risk of developing malignancy, a set of biopsies of oral premalignant lesions (leukoplakia, erythroplakia) were retrospectively chosen for polysomy analysis from two groups of individuals: one group who subsequently developed oral cancer and one group who did not develop oral cancer. Three of the five individuals who showed significant chromosome polysomies in their biopsies subsequently developed oral cancer, whereas only one of eight individuals with little evidence of polysomy subsequently progressed to oral cancer. These results suggest that evidence of generalized genetic change or instability might be useful as a genetic biomarker for risk assessment.
AB - Upper aerodigestive tract tumorigenesis has been hypothesized to represent a field cancerization process with multistep events based on its association with known carcinogens, its frequent associated premalignant lesions, and its multifocal clinical manifestation. To further explore this working hypothesis, we have examined normal tissue and premalignant lesions in the field of tumors for evidence of genetic change. Paraffin sections of head and neck tumors harboring neighboring premalignant lesions were explored for the presence of chromosome polysomies using in situ hybridization and chromosome-specific centromeric probes. Cells exhibiting random polysomy were observed in the premalignant regions near the tumors. The frequency of polysomy in the tumor field increased as the tissue progressed from normal morphology (33%), to hyperplasia (67%), to dysplasia (95%), and to squamous cell carcinoma (96%). These results support the notions of field cancerization and multistep tumorigenesis in the aerodigestive tract. To determine whether the degree of accumulated genetic alterations might serve as a biomarker for risk of developing malignancy, a set of biopsies of oral premalignant lesions (leukoplakia, erythroplakia) were retrospectively chosen for polysomy analysis from two groups of individuals: one group who subsequently developed oral cancer and one group who did not develop oral cancer. Three of the five individuals who showed significant chromosome polysomies in their biopsies subsequently developed oral cancer, whereas only one of eight individuals with little evidence of polysomy subsequently progressed to oral cancer. These results suggest that evidence of generalized genetic change or instability might be useful as a genetic biomarker for risk assessment.
KW - field cancerization
KW - head and neck cancer
KW - in situ hybridization
KW - leukoplakia
KW - multistep carcinogenesis
KW - polysomy
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U2 - 10.1002/jcb.240531034
DO - 10.1002/jcb.240531034
M3 - Article
C2 - 8412199
AN - SCOPUS:0027480672
VL - 53
SP - 233
EP - 236
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
SN - 0730-2312
IS - S17F
ER -