Overexpression of CIP2A in Head and Neck Cutaneous SCC

Abstract

Objective: Determine if 1) Cancerous Inhibitor of Phosphoprotein 2A (CIP2A), which increases c-myc activity by inhibiting the c-myc inhibitor Phosphoprotein 2A (PP2A), is overexpressed in cutaneous squamous cell carcinoma of the head and neck (cSCCHN). 2) PP2A expression is altered in cSCCHN.

Method: Specimens of normal skin, early stage cSCCHN, late stage primary cSCCHN, and metastatic cSCCHN were sectioned and subjected to immunofluorescence staining for CIP2A and PP2A. CIP2A and PP2A expression was quantitated using the validated open-source software CellProfiler. Expression changes were assessed with ANOVA and Bonferroni tests, with p < 0.05 denoting significance.

Results: A total of 38 specimens were examined (5 normal skin, 9 early stage cSCCHN, 12 late stage cSCCHN, and 12 metastatic cSCCHN). CIP2A was significantly overexpressed in early stage cSCCHN relative to normal skin (30.0 vs 17.7% of cells positive for CIP2A, P = .049), while expression was even higher in late stage primary cSCCHN (46.3% positive) and metastatic cSCCHN (49.4% positive, P = .004 vs normal, ANOVA among all 4 groups: P = .002). However, PP2A expression was completely unchanged among all 4 groups (P = .9754 by ANOVA).

Conclusion: While PP2A expression is unchanged, CIP2A is overexpressed in cSCCHN, and increasing expression of CIP2A is correlated with metastatic progression of cSCCHN. Thus, CIP2A activity may be important to cSCCHN tumorigenesis and serve both as a prognostic marker and as a novel target for new therapeutic agents.