Prognostic utility of chromosomal instability detected by fluorescence in situ hybridization in fine-needle aspirates from oral squamous cell carcinomas

Abstract

Background: Although chromosomal instability (CIN) has been detected in many kinds of human malignancies by means of various methods, there is no practical assessment for small clinical specimens. In this study, we evaluated CIN in fine-needle aspiration (FNA) biopsied oral squamous cell carcinomas (SCCs) using fluorescence in situ hybridization (FISH) analysis, and investigated its prognostic significance.

Methods: To evaluate CIN status of tumors, FISH with genomic probes for the centromeres of chromosomes 7, 9, and 11 was performed on specimens obtained by FNA from 77 patients with primary oral SCCs.

Results: High-grade CIN (CIN3) was observed in 11.7% (9/77) of patients with oral SCCs and was associated significantly with reduced disease-free survival (p = .008) and overall survival (p = .003). Multivariate Cox proportional hazards analysis showed that CIN status was significantly correlated with disease-free survival (p = .035) and overall survival (p = .041).

Conclusion: Analysis of CIN status using FISH on FNA biopsy specimens may be useful in predicting of recurrence and poor prognosis in patients with oral SCCs.

Figure 1

Representative FISH analysis. Cells were hybridized with probes for the chromosome 7, 9, or 11 centromere (green or orange). (A) A representative example of a normal lymphocyte; hybridized with single probe for the chromosome 11 centromere (green). FISH analysis revealed two copies of centromeric signal in all nucleus. (B) High-grade CIN case. Note the presence of heterogeneous copy number of the centromeric signal of chromosome 9.

Figure 2

Disease-free and Overall survival of 77 patients of oral SCCs according to CIN status. A, Kaplan-Meier curve for disease-free survival according to CIN status. B, Kaplan-Meier curve for overall survival according to CIN status.