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

J Am Acad Dermatol. 2019 Mar;80(3):626-632.e1. doi: 10.1016/j.jaad.2018.10.018. Epub 2018 Oct 22.

Abstract

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.

Keywords: biomarker; cancer tumor marker; cutaneous squamous cell carcinoma; inositol polyphosphate-5-phosphatase; metastases; outcome; prognosis; prognostic marker; recurrence; squamous cell carcinoma; staging.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / secondary*
  • Female
  • Humans
  • Inositol Polyphosphate 5-Phosphatases / metabolism*
  • Keratosis, Actinic / metabolism*
  • Keratosis, Actinic / pathology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Peripheral Nerves / pathology
  • Prognosis
  • Retrospective Studies
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology*
  • Survival Rate
  • Tumor Burden

Substances

  • Biomarkers, Tumor
  • INPP5A protein, human
  • Inositol Polyphosphate 5-Phosphatases