Prognostic Value of INPP5A Expression in Recurrent and Metastatic Disease

Squamous cell carcinoma
Squamous cell carcinoma
Low immunohistochemical staining expression of INPP5A predicts poor overall survival in recurrent and metastatic cutaneous squamous cell carcinoma.

Loss of inositol polyphosphate-5-phosphatase (INPP5A) expression predicts poor overall survival in recurrent and metastatic disease (RMD) of cutaneous squamous cell carcinoma (cSCC), according to a study published in the Journal of the American Academy of Dermatology.

RMD of cSCC is associated with poor outcomes, but there are currently no available biomarkers to stratify risk in this population. Because INPP5A has been found to play a role in the progression of actinic keratosis to cSCC and localized disease to metastatic disease, this multicenter, retrospective Mayo Clinic Health System cohort study was designed to determine the prognostic value of INPP5A as a method for risk-stratifying RMD.

Immunohistochemical staining was used to examine the protein expression of cSCC INPP5A in primary tumors and RMD. Levels of protein expression were scored on a 4-point scale from 0 to 3 by dermatologists and dermatopathologists who were blinded to patient outcomes. Normal expression was defined as an INPP5A score of 3, partially diminished expression as a score of 2, significantly diminished as a score of 1, and complete loss as score of 0. All levels of expression were compared with adjacent normal epidermis. Low staining expression (LSE) was classified as scores of 0 or 1, and high staining expression (HSE) as scores of 2 or 3.

In the study, 50 patients with RMD cSCC were examined, yielding 52 tumors and 64 events (32 local metastases, 27 local recurrence, and 5 distant metastases). Of the primary tumors, 78.8% had HSE and 21.2% had LSE; of the RMD, 69.2% had HSE and 30.8% had LSE. LSE of INPP5A of RMD was associated with poor overall survival of 31.0 months compared with 62.0 months for HSE (P =.0272). A composite risk score (CRS; CRS=primary + RMD; with HSE=0 and LSE=1; range, 0-2) of 0 was predictive of improved overall outcomes compared with a CRS of >1 (HR, 0.42; 95% CI, 0.21-0.84; P =.0113). This remained significant in the subanalysis.

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Study limitations included the multicenter but single-institution design with a population of only white participants. In addition, it was underpowered to detect differences in the outcome of INPP5A at the primary tumor level, and the metastatic cohort was at a significantly more advanced stage than the recurrent cohort.

Nevertheless, study investigators concluded that the “loss of INPP5A expression predicts poor [overall survival] in RMD of cSCC. INPP5A CRS of 0 is associated with a superior [overall survival] of locally recurrent cSCC. Our study demonstrates the potential for INPP5A expression level to be used as an adjunct tumor marker for clinical management and risk stratification of locally RMD disease in cSCC. An additional study with a larger cohort is justified in order to determine if INPP5A expression may serve as a biomarker to stratify [overall survival] in individuals with metastatic disease.”

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Maly CJ, Cumsky HJL, Costello CM, et al. Prognostic value of inositol polyphosphate-5-phosphatase expression in recurrent and metastatic cutaneous squamous cell carcinoma [published online August 19, 2019]. J Am Acad Dermatol. doi:10.1016/j.jaad.2019.08.027