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Malignancy detection by molecular cytogenetics in clinically normal mucosa adjacent to head and neck tumors
J E Barrera1, H Ai, Z Pan
1Department of Otolaryngology-Head and Neck Surgery, University of Colorado Health Sciences Center, Denver 80262, USA. barreraj@york.uchsc.edu
Objective:
To identify the potential use of chromosome imbalances as biomarkers for tumorigenesis in head and neck squamous cell carcinoma (HNSCC) by fluorescence in situ hybridization (FISH).
Design:
In this case-control study, chromosome copy numbers were assessed in dual-target, dual-color FISH assays using DNA probes specific for 14 human chromosomes (1, 2, 3, 6, 7, 8, 9, 10, 11, 12, 15, 17, X, and Y) applied to exfoliated epithelial cells.
Setting:
University medical center.
Patients:
We examined 20 cell brushings (from 10 primary tumors and 10 clinically normal margins) collected from 10 patients with HNSCC and compared these with cell brushings from the oral cavity of 10 nonsmoker and 10 smoker control subjects.
Intervention:
None.
Main Outcome Measure:
Chromosomal aneuploidy.
Results:
Specimens from nonsmokers displayed greater than 91% of cells with normal signals, indicating high analytical sensitivity for the probes. Specimens from smokers demonstrated large variability without significant imbalance (P>.05) compared with those from nonsmokers. Tumor specimens from patients with HNSCC displayed significant chromosomal imbalance (P<.05) for all probes except chromosome Y. Similar imbalance, although in lower frequency, was found in all clinically normal adjacent mucosa specimens.
Conclusions:
Interphase FISH demonstrated great applicability in detecting chromosome imbalance associated with malignancy in HNSCC and clinically normal adjacent cells, thereby detecting subclinical tumorigenesis. A panel of chromosome probes (chromosomes 3, 8, 9, and 10) is proposed as an efficient and sensitive additional tool for future routine screening of tumor margins and potential diagnosis of residual disease in HNSCC.