Abstract
Oral squamous cell carcinoma (OSCC) is considered an aggressive malignancy, mainly due to its increased propensity to provide local and distant lymph node metastases. Gross chromosome instability (CI; polysomy/aneuploidy/monosomy), combined or not with specific gene alterations, is implicated in the development and progression of solid malignancies, including OSCC. In order to further study the relationship between these genetic alterations and the aggressive biological behavior of OSCCs, we investigated the frequency and impact of chromosome 9 numerical imbalances in these tumors. Fifty (n = 50) formalin-fixed, paraffin-embedded primary OSCC tissue sections were used. Chromogenic in situ hybridization (CISH) was implemented for detecting chromosome 9 (CEN—centromere enumeration) numerical alterations. Concerning the screening process in CISH slides, a novel, real-time reference and calibration grid platform was implemented. Chromosome 9 polysomy was observed in 8/50 (16%) tissue sections, whereas the rest of them demonstrated a normal, diploid pattern (42/50; 84%). Chromosome 9 polysomy was associated with the grade of differentiation of the examined tumors (p = 0.036). Chromosome 9 numerical imbalances (polysomy) were observed in sub-groups of OSCCs correlating with a progressive dedifferentiation of the malignant tissues. Concerning the implementation of the proposed grid-based platform as described above on CISH slides, it provides a novel, fast, and accurate screening mapping mechanism for detecting chromosome numerical imbalances.
Highlights
Development and implementation of modern molecular biology techniques has led to the detection of a broad spectrum of genomic imbalances in solid malignancies
Chromosome 9 polysomy was associated with the grade of differentiation of the examined tumors (p = 0.036)
There was no significant correlation between chromosome 9 numerical imbalances and age of the examined patients (p = 0.201)
Summary
Development and implementation of modern molecular biology techniques has led to the detection of a broad spectrum of genomic imbalances in solid malignancies. Various gross chromosome instabilities (CIs), such as polysomy/aneuploidy/aneusomy, either combined or not with specific gene deregulation mechanisms, including point mutations, deletions, and amplification, have been noted in these tumors. These critical genetic events have been associated with alterations of the prognosis and the response rates to novel targeted therapeutic regimens in the corresponding patients [1]. Oral squamous cell carcinoma (OSCC) is the most frequent type of malignancy This pathological entity is frequently characterized by an aggressive phenotype due to an increased tendency to present local and distant lymph node metastases, apparently as a result of severe genetic alterations [2]. Various etiopathogenetic factors have been associated with OSCC development and progression including tobacco, chronic alcohol consumption, and viral-mediated deregulation [3,4]
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