Role of Superoxide
Dismutase in Spinocellular Carcinoma of Head and Neck - a Pilot Study
Salzman R.1, Kostřica R.1, Pácal L.2, Tomandl J.3, Kaňková K.2, Horáková Z.1
Klinika otorinolaryngologie a chirurgie hlavy a krku LF MU a FN u sv. Anny, Brno, přednosta prof. MUDr. R. Kostřica, CSc.1 Ústav patologické fyziologie a LF MU, Brno2 Biochemický ústav LF MU, Brno3 |
|
Summary:
Introduction: Oxidative status plays an important role in cancer development. Our aim is to investigate relationship
between genetic variants encoding for antioxidant enzymes; activity of the expressed enzyme and
clinical stage of head and neck squamous cell carcinoma (HNSCC).
Material and Methods: prospective study of 75 patients treated with head&neck squamous cell carcinoma at
St. Anne’s University Hospital in Brno from July 2005 to August 2006. PCR-based methodology was used to
detect genotype of the manganese superoxide dismutase (SOD) Ala16Val polymorphism.We measured activity
of superoxide dismutase in plasma (p-SOD) and in erythrocytes (ery-SOD). Using high performance liquid
chromatography we analyzed malondialdehyde (MDA) in plasma.Tumor necrosis factor (TNF) in plasma was
measured by the ultrasensitive ELISA.
Results: Our study revealed significantly lower p-SOD level in patients without metastatic spread to neck
lymph nodes (n=30) in comparison to N+ patients (n=45, p=0.02, Mann-Whitney). Increased plasmatic MDA
was found in patients with recurrent disease (n=13) in 22 months following complete remission (CR) when
compared to those who remained in CR (n=58, remaining 4 patients didn’t reach CR, p=0.06, Mann-Whitney).
Subjects with MDA < 0.25nmol/g manifested longer disease free interval than those with MDA > 0.25nmol/g
(log rank test, p = 0.01). Patients with MDA level > 0.25nmol/g face 42.9% risk of recurrence in contrast to patients
with MDA < 0.25nmol/g with a risk of 8.0% (p=0.01, χ2 test). Furthermore, our study revealed that patients
with p-SOD level < 1.3kU/g suffer from metastases in neck lymph nodes in 49.7% in contrast to 77.1% in those
with p-SOD > 1.3kU/g (p=0.03, χ2 test). Frequences of the Ala-9Val alleles were 58.8% Ala and 41.2% Val. Genotype
distribution for the Ala/Val genetic polymorphism fits predictions for Hardy-Weinberg equilibrium
(p=0.05, χ2 test). Activities of p-SOD revealed significant differences when comparing groups representing different
genetic variants of SOD polymorphism (p=0.05, Kruskal-Wallis). Otherwise, there were no significant
associations between patient groups divided by locoregional metastatic spread to neck lymph nodes, patients
in CR and those with recurrence or holders of different genetic variants of the Ala-9Val polymorphism. Neither
alleles distribution showed differences when comparing afore-mentioned groups.
Conclusions: Our results entitle us to hypothesize the important role of oxidative stress in head and neck
oncology. Validation of our preliminary results could bring major changes to decision making in dealing with
head and neck cancer. The coming research should focus on prognostication role of MDA in recurrent disease
and value of SOD activity as a marker of metastatic potential
Key words:
oxidative stress, head and neck squamous cell carcinoma, superoxidedismutase, malondialdehyd,
metastatic potential, prognostication factor
|