Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun;51(6):450-458.
doi: 10.1111/cup.14590. Epub 2024 Feb 29.

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

Michael H Alexander  1   2   3 , William J Cousins  1   2 , Tom Ewen  1   2 , Andrew P South  3 , Penny Lovat  1   2 , Niki Stefanos  4
Affiliations

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

Michael H Alexander et al. J Cutan Pathol. 2024 Jun.

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.

Keywords: autophagy; biomarker; cSCC.

PubMed Disclaimer

References

REFERENCES

    1. Yang DD, Borsky K, Jani C, et al. Trends in keratinocyte skin cancer incidence, mortality and burden of disease in 33 countries between 1990 and 2017. Br J Dermatol. 2023;188(2):237‐246. doi:10.1093/bjd/ljac064
    1. Simonacci F, Bertozzi N, Grieco MP, Grignaffini E, Raposio E. Surgical therapy of cutaneous squamous cell carcinoma: our experience. Acta Biomed. 2018;89(2):242‐248. doi:10.23750/abm.v89i2.6189
    1. van Lee CB, Roorda BM, Wakkee M, et al. Recurrence rates of cutaneous squamous cell carcinoma of the head and neck after Mohs micrographic surgery vs. standard excision: a retrospective cohort study. Br J Dermatol. 2019;181(2):338‐343. doi:10.1111/bjd.17188
    1. Rabinowits G, Migden MR, Schlesinger TE, et al. Evidence‐based consensus recommendations for the evolving treatment of patients with high‐risk and advanced cutaneous squamous cell carcinoma. JID Innov. 2021;1(4):100045. doi:10.1016/j.xjidi.2021.100045
    1. Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: incidence, risk factors, diagnosis, and staging. J Am Acad Dermatol. 2018;78(2):237‐247. doi:10.1016/j.jaad.2017.08.059

MeSH terms

LinkOut - more resources