Document Type
Article
Publication Date
2-29-2024
Abstract
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.
Recommended Citation
Alexander, Michael H.; Cousins, William J.; Ewen, Tom; South, Andrew P.; Lovat, Penny; and Stefanos, Niki, "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" (2024). Department of Dermatology and Cutaneous Biology Faculty Papers. Paper 218.
https://jdc.jefferson.edu/dcbfp/218
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
PubMed ID
38421158
Language
English
Comments
This article is the author’s final published version in the Journal of Cutaneous Pathology, Volume 51, Issue 6, June 2024, Pages 450-458.
The published version is available at https://doi.org/10.1111/cup.14590. Copyright © 2024 AMLo Biosciences Ltd. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.
Publication made possible in part by support through a transformative agreement between Thomas Jefferson University and the publisher.