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The combined immunohistochemical expression of AMBRA1 and SQSTM1 identifies patients with poorly differentiated cutaneous squamous cell carcinoma at risk of metastasis: A proof of concept study

Lookup NU author(s): Michael Alexander, Will Cousins, Dr Tom Ewen, Professor Penny Lovat



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2024 AMLo Biosciences Ltd. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.Background: Cutaneous squamous cell carcinoma (cSCC) incidence continues to increase globally with, as of yet, an unmet need for reliable prognostic biomarkers to identify patients at increased risk of metastasis. The aim of the present study was to test the prognostic potential of the combined immunohistochemical expression of the autophagy regulatory biomarkers, AMBRA1 and SQSTM1, to identify high-risk patient subsets. Methods: A retrospective cohort of 68 formalin-fixed paraffin-embedded primary cSCCs with known 5-year metastatic outcomes were subjected to automated immunohistochemical staining for AMBRA1 and SQSTM1. Digital images of stained slides were annotated to define four regions of interest: the normal and peritumoral epidermis, the tumor mass, and the tumor growth front. H-score analysis was used to semi-quantify AMBRA1 or SQSTM1 expression in each region of interest using Aperio ImageScope software, with receiver operator characteristics and Kaplan–Meier analysis used to assess prognostic potential. Results: The combined loss of expression of AMBRA1 in the tumor growth front and SQSTM1 in the peritumoral epidermis identified patients with poorly differentiated cSCCs at risk of metastasis (*p < 0.05). Conclusions: Collectively, these proof of concept data suggest loss of the combined expression of AMBRA1 in the cSCC growth front and SQSTM1 in the peritumoral epidermis as a putative prognostic biomarker for poorly differentiated cSCC.

Publication metadata

Author(s): Alexander MH, Cousins WJ, Ewen T, South AP, Lovat P, Stefanos N

Publication type: Article

Publication status: Published

Journal: Journal of Cutaneous Pathology

Year: 2024

Pages: epub ahead of print

Online publication date: 29/02/2024

Acceptance date: 09/01/2024

Date deposited: 03/04/2024

ISSN (print): 0303-6987

ISSN (electronic): 1600-0560

Publisher: John Wiley and Sons Inc


DOI: 10.1111/cup.14590


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