ATM in oral carcinogenesis: association with clinicopathological features

Abstract

Purpose: The ataxia telangiectasia mutated (ATM) gene plays a critical role in DNA damage response. Our aim here was to investigate the expression profile and loss of heterozygosity (LOH) of ATM, as well as their relationships to clinicopathological parameters in oral premalignant lesions (leukoplakia) and primary oral squamous cell carcinoma (OSCC).

Methods: Immunohistochemical assay and PCR were performed to detect the expression profile and LOH at D11S2179 of ATM. The association between clinicopathological parameters and the changes of ATM was statistically analyzed.

Results: ATM protein levels were higher in oral leukoplakia than those in normal controls, while the expressions of ATM protein had a versatile tendency in OSCC: 10 samples (31.25%) showed increased ATM protein levels than those observed in normal tissues, 12 samples (37.50%) had the same protein levels as the normal tissues, and 10 samples (31.25%) showed reduced or absent ATM levels. The patients with reduced/absent ATM expression had more poorly-differentiated situation as well as the tendency for lymph node metastasis. Most interestingly, 50% of these reduced cases were younger than 50 years old. PCR for LOH assay displayed that none of the samples from oral leukoplakia had abnormal changes in D11S2179, while three samples (9.38%) of OSCC showed loss of heterozygosity, and two samples (6.25%) with microsatellite instability.

Conclusions: These findings suggest that overexpression of ATM may be one of the early events in the carcinogenesis of OSCC. ATM might be a candidate biomarker for diagnosis and prognosis in OSCC, as well as a possible genetic marker for early-onset OSCC.

Fig. 1

The immunohistochemical staining of ATM in normal mucosa. The gingival mucosa was shown. Left: HE staining (×100), middle and right: IHC staining (middle ×100, right ×400)

Fig. 2

ATM expression was increased in oral leukoplakia. Left: mild dysplasia; middle: moderate dysplasia; right: severe dysplasia (IHC, ×100)

Fig. 3

Different levels of ATM expression in OSCC. From the top down: ATM negative, low, moderate or high levels are shown. Left panels ×40, right panels ×200