ESTRO 2024 - Abstract Book

S1544

Clinical - Lower GI

ESTRO 2024

2415

Proffered Paper

Unraveling the Prognostic Significance of HIF-1α in Anal Squamous Cell Cancer

Svetlana Warkentin 1 , Edgar Dahl 1 , Michael Eble 2 , Danny Jonigk 1 , Ahmed Allam Mohamed 2

1 RWTH Aachen University Hospital, Department of Pathology, Aachen, Germany. 2 RWTH Aachen University Hospital, Department of Radiation Oncology, Aachen, Germany

Purpose/Objective:

The incidence and mortality of anal squamous cell cancer (ASCC) have seen a recent uptick in Western countries (1). This phenomenon can be attributed, at least in part, to the rise in prevalence of the human papillomavirus (HPV) and the contribution of the human immune deficiency virus (HIV) in the rise of ASCC cases. For decades, The treatment paradigm for ASCC has remained largely unchanged, with concurrent radiation, fluoropyrimidine, and mitomycin or cisplatin as the main modality of the treatment applied universally. However, in the realm of tumor biology, there has been an unmet need to explore underground mechanisms for therapy resistance and identify biomarkers that can guide personalized treatment strategies for individual patients. Hypoxia-inducible factor 1 alpha (HIF-1α) is a transcription factor that has emerged as a central figure in the complex landscape of cancer biology. Its significance lies in its capacity to orchestrate a myriad of cellular responses to the hypoxic microenvironments found in solid tumors (2). HIF-1α plays a pivotal role in adapting cancer cells to low oxygen levels, enabling them to thrive, resist treatment, and promote aggressive phenotypes (2). Remarkably, the expression of HIF-1α in ASCC and its consequent implication have remained unexplored until now. In the current analysis, we investigate the expression of HIF-1α in ASCC and its potential as a prognostic indicator.

Material/Methods:

Clinical data from patients with ASCC treated in our center were collected as previously reported (3,4). For the current analysis, we specifically included patients for whom archived paraffinized specimens were available at our center. Immunohistochemistry was performed on representative tissue sections using a commercial monoclonal rabbit antibody targeting HIF-1α (EP118, HIF-1 alpha antibody, Bio SB, 108 Santa Barbara, CA 93111, USA). To ensure accuracy, a positive control for full expression served as a reference point for quantifying HIF-1α expression in the examined specimens. We employed Receiver Operating Characteristic (ROC) analysis to determine an optimal cut off point, enabling us to categorize the patients into “HIF-1α low” and “HIF-1α high” groups.

Results:

For the current analysis, we were able to obtain archived paraffin-embedded specimens from 25 patients as summarized in Table 1. These patients received treatment between January 2009 and December 2022. All patients received radiation therapy as intensity-modulated radiation therapy (IMRT) concurrent with fluoropyrimidine and mitomycin, except one geriatric patient who underwent radiotherapy alone (Table 1). The median follow-up for the patients, as represented by the interquartile range (IQR) was 63.43 (27.83;88.13) months.