The prognostic value of inositol polyphosphate 5-phosphatase in cutaneous squamous cell carcinoma

Background: Inositol polyphosphate 5-phosphatase (INPP5A) has been shown to play a role in development and progression of cutaneous squamous cell carcinoma (cSCC). The goal of the current study was to explore the prognostic value of INPP5A expression in cSCC. Methods: A total of 189 cases of actinic keratosis and SCC in 174 patients were identified; clinical and outcome data were abstracted, histopathology was rereviewed, and immunohistochemical staining and interpretation was performed for INPP5A. Results: The majority of tumors (89.4%) had an INPP5A score of 2 or 3. No patients had complete loss of INPP5A. Tumors with an INPP5A score of 1 were more likely to be intermediate- to high-risk tumors (Brigham and Women's Hospital stage ≥T2a 85.0% vs 23.7% [P <.0001]) characterized by a larger diameter (2.4 cm vs 1.3 cm [P =.0004]), moderate-to-poor differentiation (86.7% vs 17.6% [P <.0001]), and perineural invasion (37.5% vs 5.3%, [P <.0001]). An INPP5A score of 1 was associated with a worse 3-year survival (a rate of 42.3% [hazard ratio, 2.81, P =.0006]) and a local metastasis rate of 48.0% (hazard ratio, 4.71; P <.0001). Conclusions: Low INPP5A scores are predictive of aggressive tumors and may be a useful adjunct to guide clinical management of cSCC.