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Cysteine cathepsins and stefins in head and neck cancer: an update <strong>of</strong><br />
clinical studies<br />
Primož Strojan<br />
Dept. <strong>of</strong> Radiation Oncology, Institute <strong>of</strong> Oncology, Zaloška 2, SI-1000 Ljubljana, Slovenia<br />
To distinguish biologically more aggressive and less aggressive head and neck carcinomas<br />
within each traditional risk category, numerous new prognostic factors were evaluated on<br />
genetic, mRNA or protein levels. The recent implementation <strong>of</strong> microarray technology<br />
for biological pr<strong>of</strong>iling <strong>of</strong> tumors confirmed the multifactorial origin <strong>of</strong> carcinogenesis.<br />
Among the factors that promote tumor growth and invasion, several protease systems,<br />
involved in proteolytic degradation <strong>of</strong> extracellular matrix components, were studied,<br />
including papain-like lysosomal cysteine proteases, such as cathepsins B and L, and their<br />
physiological inhibitors cystatins, such as cystatin C, stefin A and stefin B.<br />
Alterations in the expression <strong>of</strong> cystatins at mRNA and protein levels, as well as in<br />
trafficking and activity were reported in malignant and stromal cells compared to normal<br />
counterparts in a variety <strong>of</strong> tumors. These alterations were found to correlate with the<br />
malignant phenotype <strong>of</strong> the tumor in vitro and in vivo. In a clinical setting, the observed<br />
correlation with treatment efficacy and patient survival was suggestive <strong>of</strong> their predictive<br />
and/or prognostic role in some cancer types.<br />
In our previous studies on operable head and neck carcinoma, high levels <strong>of</strong> cysteine<br />
protease inhibitors in tumor tissue homogenates appeared as prognostically advantageous.<br />
Specifically, in two independent, but smaller prospective cohorts <strong>of</strong> patients, this<br />
relationship was confirmed for stefin A, stefin B and for cystatin C. To the contrary,<br />
cysteine cathepsins failed to show any potential to predict survival in the same group <strong>of</strong><br />
patients. Data on the immunohistochemically determined expression pr<strong>of</strong>ile <strong>of</strong> cysteine<br />
cathepsins is scanty and available only for oral cavity tumors, but not also for pharyngeal<br />
or laryngeal carcinomas; the same finding was also arrived at in the case <strong>of</strong> their possible<br />
prognostic significance. So far, to the best <strong>of</strong> our knowledge, stefins have not been subjected<br />
to immunohistochemical<br />
l48<br />
evaluation in any <strong>of</strong> the studies conducted on head and neck<br />
carcinomas.<br />
At the conference, the results from recent studies analysing the predictive and prognostic<br />
role <strong>of</strong> cysteine cathepsins B and L and stefins A and B in operable and inoperable squamous<br />
cell carcinoma <strong>of</strong> the head and neck will be presented and discussed.<br />
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