Prognostic value of inositol polyphosphate-5-phosphatase expression in recurrent and metastatic cutaneous squamous cell carcinoma

Connor J. Maly, Helen J.L. Cumsky, Collin M. Costello, Jessica E. Schmidt, Richard J. Butterfield, Nan Zhang, David J. DiCaudo, Steven A. Nelson, Maxwell L. Smith, Shari A. Ochoa, Christian L. Baum, Thomas H. Nagel, Mark R. Pittelkow, Aleksandar Sekulic, Aaron R. Mangold

Research output: Contribution to journalArticle

Abstract

Background: Inositol polyphosphate-5-phosphatase (INPP5A) has been shown to play a role in the progression of actinic keratosis to cutaneous squamous cell carcinoma (cSCC) and the progression of localized disease to metastatic disease. Currently, no cSCC biomarkers are able to risk stratify recurrent and metastatic disease. Objective: To determine the prognostic value of INPP5A expression in cSCC recurrent and metastatic disease. Methods: We conducted a multicenter, single-institutional, retrospective cohort study within the Mayo Clinic Health System on the use of immunohistochemical staining to examine cSCC INPP5A protein expression in primary tumors and recurrent and metastatic disease. Dermatologists and dermatopathologists were blinded to outcome. Results: Low staining expression of INPP5A in recurrent and metastatic disease tumors was associated with poor overall survival (OS) (31.0 months for low versus 62.0 months for high expression; P =.0272). A composite risk score (calculated as score of primary tumor + score of recurrent or metastatic disease tumor, with tumors with high expression scoring a zero and low expression a 1, score range 0-2) of 0 was predictive of improved OS compared with a composite risk score of ≥1 (hazard ratio 0.42, 95% confidence interval 0.21-0.84; P =.0113). Limitations: This is a multicenter but single institution study of a white population. Conclusion: Loss of INPP5A expression predicts poor OS in recurrent and metastatic disease of cSCC.

Original languageEnglish (US)
JournalJournal of the American Academy of Dermatology
DOIs
StateAccepted/In press - Jan 1 2019

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Squamous Cell Carcinoma
Skin
Neoplasms
Staining and Labeling
Actinic Keratosis
Inositol Polyphosphate 5-Phosphatases
Disease Progression
Cohort Studies
Retrospective Studies
Biomarkers
Confidence Intervals
Health
Population
Proteins

Keywords

  • IHC
  • immunohistochemistry
  • inositol polyphosphate-5-phosphatase
  • INPP5A
  • SCC
  • squamous cell carcinoma

ASJC Scopus subject areas

  • Dermatology

Cite this

Prognostic value of inositol polyphosphate-5-phosphatase expression in recurrent and metastatic cutaneous squamous cell carcinoma. / Maly, Connor J.; Cumsky, Helen J.L.; Costello, Collin M.; Schmidt, Jessica E.; Butterfield, Richard J.; Zhang, Nan; DiCaudo, David J.; Nelson, Steven A.; Smith, Maxwell L.; Ochoa, Shari A.; Baum, Christian L.; Nagel, Thomas H.; Pittelkow, Mark R.; Sekulic, Aleksandar; Mangold, Aaron R.

In: Journal of the American Academy of Dermatology, 01.01.2019.

Research output: Contribution to journalArticle

Maly, Connor J. ; Cumsky, Helen J.L. ; Costello, Collin M. ; Schmidt, Jessica E. ; Butterfield, Richard J. ; Zhang, Nan ; DiCaudo, David J. ; Nelson, Steven A. ; Smith, Maxwell L. ; Ochoa, Shari A. ; Baum, Christian L. ; Nagel, Thomas H. ; Pittelkow, Mark R. ; Sekulic, Aleksandar ; Mangold, Aaron R. / Prognostic value of inositol polyphosphate-5-phosphatase expression in recurrent and metastatic cutaneous squamous cell carcinoma. In: Journal of the American Academy of Dermatology. 2019.
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title = "Prognostic value of inositol polyphosphate-5-phosphatase expression in recurrent and metastatic cutaneous squamous cell carcinoma",
abstract = "Background: Inositol polyphosphate-5-phosphatase (INPP5A) has been shown to play a role in the progression of actinic keratosis to cutaneous squamous cell carcinoma (cSCC) and the progression of localized disease to metastatic disease. Currently, no cSCC biomarkers are able to risk stratify recurrent and metastatic disease. Objective: To determine the prognostic value of INPP5A expression in cSCC recurrent and metastatic disease. Methods: We conducted a multicenter, single-institutional, retrospective cohort study within the Mayo Clinic Health System on the use of immunohistochemical staining to examine cSCC INPP5A protein expression in primary tumors and recurrent and metastatic disease. Dermatologists and dermatopathologists were blinded to outcome. Results: Low staining expression of INPP5A in recurrent and metastatic disease tumors was associated with poor overall survival (OS) (31.0 months for low versus 62.0 months for high expression; P =.0272). A composite risk score (calculated as score of primary tumor + score of recurrent or metastatic disease tumor, with tumors with high expression scoring a zero and low expression a 1, score range 0-2) of 0 was predictive of improved OS compared with a composite risk score of ≥1 (hazard ratio 0.42, 95{\%} confidence interval 0.21-0.84; P =.0113). Limitations: This is a multicenter but single institution study of a white population. Conclusion: Loss of INPP5A expression predicts poor OS in recurrent and metastatic disease of cSCC.",
keywords = "IHC, immunohistochemistry, inositol polyphosphate-5-phosphatase, INPP5A, SCC, squamous cell carcinoma",
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TY - JOUR

T1 - Prognostic value of inositol polyphosphate-5-phosphatase expression in recurrent and metastatic cutaneous squamous cell carcinoma

AU - Maly, Connor J.

AU - Cumsky, Helen J.L.

AU - Costello, Collin M.

AU - Schmidt, Jessica E.

AU - Butterfield, Richard J.

AU - Zhang, Nan

AU - DiCaudo, David J.

AU - Nelson, Steven A.

AU - Smith, Maxwell L.

AU - Ochoa, Shari A.

AU - Baum, Christian L.

AU - Nagel, Thomas H.

AU - Pittelkow, Mark R.

AU - Sekulic, Aleksandar

AU - Mangold, Aaron R.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Inositol polyphosphate-5-phosphatase (INPP5A) has been shown to play a role in the progression of actinic keratosis to cutaneous squamous cell carcinoma (cSCC) and the progression of localized disease to metastatic disease. Currently, no cSCC biomarkers are able to risk stratify recurrent and metastatic disease. Objective: To determine the prognostic value of INPP5A expression in cSCC recurrent and metastatic disease. Methods: We conducted a multicenter, single-institutional, retrospective cohort study within the Mayo Clinic Health System on the use of immunohistochemical staining to examine cSCC INPP5A protein expression in primary tumors and recurrent and metastatic disease. Dermatologists and dermatopathologists were blinded to outcome. Results: Low staining expression of INPP5A in recurrent and metastatic disease tumors was associated with poor overall survival (OS) (31.0 months for low versus 62.0 months for high expression; P =.0272). A composite risk score (calculated as score of primary tumor + score of recurrent or metastatic disease tumor, with tumors with high expression scoring a zero and low expression a 1, score range 0-2) of 0 was predictive of improved OS compared with a composite risk score of ≥1 (hazard ratio 0.42, 95% confidence interval 0.21-0.84; P =.0113). Limitations: This is a multicenter but single institution study of a white population. Conclusion: Loss of INPP5A expression predicts poor OS in recurrent and metastatic disease of cSCC.

AB - Background: Inositol polyphosphate-5-phosphatase (INPP5A) has been shown to play a role in the progression of actinic keratosis to cutaneous squamous cell carcinoma (cSCC) and the progression of localized disease to metastatic disease. Currently, no cSCC biomarkers are able to risk stratify recurrent and metastatic disease. Objective: To determine the prognostic value of INPP5A expression in cSCC recurrent and metastatic disease. Methods: We conducted a multicenter, single-institutional, retrospective cohort study within the Mayo Clinic Health System on the use of immunohistochemical staining to examine cSCC INPP5A protein expression in primary tumors and recurrent and metastatic disease. Dermatologists and dermatopathologists were blinded to outcome. Results: Low staining expression of INPP5A in recurrent and metastatic disease tumors was associated with poor overall survival (OS) (31.0 months for low versus 62.0 months for high expression; P =.0272). A composite risk score (calculated as score of primary tumor + score of recurrent or metastatic disease tumor, with tumors with high expression scoring a zero and low expression a 1, score range 0-2) of 0 was predictive of improved OS compared with a composite risk score of ≥1 (hazard ratio 0.42, 95% confidence interval 0.21-0.84; P =.0113). Limitations: This is a multicenter but single institution study of a white population. Conclusion: Loss of INPP5A expression predicts poor OS in recurrent and metastatic disease of cSCC.

KW - IHC

KW - immunohistochemistry

KW - inositol polyphosphate-5-phosphatase

KW - INPP5A

KW - SCC

KW - squamous cell carcinoma

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U2 - 10.1016/j.jaad.2019.08.027

DO - 10.1016/j.jaad.2019.08.027

M3 - Article

C2 - 31437542

AN - SCOPUS:85073159345

JO - Journal of the American Academy of Dermatology

JF - Journal of the American Academy of Dermatology

SN - 0190-9622

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