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Abstract

Background: Papillary carcinoma of the thyroid gland (PTC) is a malignant thyroid neoplasm which had a favorable prognosis; but as it is a highly invasive cancer which has a capability to invade the surrounding tissues and spread to lymph-nodes, which leads to higher incidence of recurrence of the tumor and hematogenous spread which lead to dismal patient outcome. Discovering novel prognostic bio-markers for PTC can help to detect recurrence, invasion, predicting patient outcome and the possible use as therapeutic-targets for such type of cancer. Ubiquitin-specific protease 22 (USP22), is deubiquitinating enzyme which is associated with occurrence of metastasis and resistance to therapy. Stress-induced phosphor-protein-1 (STIP-1) that is also named heat-shock-protein-(HSP, cold interact with heat shock proteins to form structures which have roles in many biological processes. Both USP22 and STIP-1 are incriminated in progression of the cell cycle.The purpose of the current study was to detect the expression levels of both USP22 and STIP-1 in samples of papillary thyroid carcinoma (PTC), to correlate their combined expression with pathological and follow-up parameters to evaluate its clinical significance in PTC patients. Methods: We evaluated USP22 and STIP-1 expression levels in sections from 30 paraffin blocks of PTC using immunohistochemistry, analyzed correlations between their expression levels, clinic-pathological and follow-up parameters of patients with PTC. Results: Increased USP22 expression was associated with larger PTC size (p=0.02 and 0.03 respectively), presence of extra-capsular invasion (p=0.004), multi-focality (p=0.002 and 0.003 respectively), extrathyroidal extension (p=0.006 and 0.009 respectively), presence of lymph node metastasis (p=0.03 and 0.034 respectively), presence of vascular invasion (p=0.008 and 0.002 respectively), presence of distant metastasis (p=0.042 and 0.006 respectively) ans advanced stage (p=0.012 and 0.018 respectively).USP22 expression was associated with higher incidence of loco-regional recurrence (LRR), neck node recurrence (p=0.26 and 0.003 respectively). PTC patients with high USP22 expression had a shorter OS & DFS when compared to patients with low USP22 expression (p=0.014 and 0.006 respectively).We have found that PTC patients with high STIP-1 expression had a shorter OS & DFS when compared to patients with low STIP-1 expression (p=0.014 and 0.043 respectively).Expressions of both USP22 and STIP-1 were significantly positively correlated with each other (p=0.01). Conclusion: Tissue protein expressions of both USP22 and STIP-1 were independent poor prognostic factors for PTC patients.