Abstract
Feline oral squamous cell carcinoma (FOSCC) is an aggressive neoplasm in cats. Little is known about the possible molecular mechanisms that may be involved in the initiation, maintenance and progression of FOSCC. Wnt signalling is critical in development and disease, including many mammalian cancers. In this study, we have investigated the expression of Wnt signalling related proteins using quantitative immunohistochemical techniques on tissue arrays. We constructed tissue arrays with 58 individual replicate tissue samples. We tested for the expression of four key Wnt/ß-catenin transcription targets, namely Cyclin D1 (CCND1 or CD1), FRA1, c-Myc and MMP7. All antibodies showed cross reactivity in feline tissue except MMP7. Quantitative immunohistochemical analysis of single proteins (expressed as area fraction / amount of tissue for normal vs tumor, mean ± SE) showed that the expression of CD1 (3.9 ± 0.5 vs 12.2 ± 0.9), FRA1 (5.5 ± 0.6 vs 16.8 ± 1.1) and c-Myc (5.4 ± 0.5 vs 12.5 ± 0.9) was increased in FOSCC tissue by 2.3 to 3 fold compared to normal controls (p<0.0001). By using a multilabel, quantitative fluorophore technique we further investigated if the co-localization of these proteins (all transcription factors) with each other and in the nucleus (stained with 4',6-diamidino-2-phenylindole, DAPI) was altered in FOSCC compared to normal tissue. The global intersection coefficients, a measure of the proximity of two fluorophore labeled entities, showed that there was a significant change (p < 0.01) in the co-localization for all permutations (e.g. CD1/FRA1 etc), except for the nuclear localization of CD1. Our results show that putative targets of Wnt signalling transcription are up-regulated in FOSCC with alterations in the co-localization of these proteins and could serve as a useful marker for the disease.
Highlights
Squamous cell carcinoma is the most common oral neoplasm in cats and people [1]
Histopathological assessment was carried out by pathologists involved in tissue procurement and subsequent to tissue array construction
Tumors were confirmed as squamous cell carcinoma (SCC), all SCC samples were moderately to well differentiated
Summary
Squamous cell carcinoma is the most common oral neoplasm in cats and people [1]. Feline oral squamous cell carcinoma (FOSCC) is a local aggressive tumor with a low metastatic rate (~15–18%) to local or regional lymph nodes but rarely to the lungs, most cats are likely to be euthanized due to the primary tumor before developing metastasis [2]. Cats living in households with smokers are considered more at risk of developing FOSCC compared to non-smoking households [3, 4]. Papilloma virus is considered another putative risk factor as in one study 90% of feline cutaneous SCC carried papillomavirus DNA [5]. FOSCC has similar tumor biology, molecular markers (p53, VEGF, EGFR) clinical outcome, treatment, and prognosis to the human counterpart [6]
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