EP735 - Demographic Factors Associated with PI3K Mutations in Anal Dysplasia and Cancer

Monday, May 12, 2025

10:25 AM – 10:30 AM PT

ePoster Presenter(s)

Hillary R. Johnson, MD

Resident Physician
University of Wisconsin - Madison
University of Wisconsin - Madison
Madison, WI, United States

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.

Author(s)

Corinne Praska, MD

General Surgery Resident
University of Wisconsin - Madison
Madison, WI, United States

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.
KD

Kirsten Dennison, MS

Researcher, Lab Manager
University of Wisconsin - Madison
Madison, Wisconsin, United States

Disclosure information not submitted.
ED

Elise C. Dietmann, B.S. Biomedical Engineering

Research Intern
University of Wisconsin-Madison
Madison, Wisconsin, United States

Disclosure information not submitted.
SM

Stephanie M. McGregor, MD PhD

Associate Professor
University of Wisconsin-Madison
Madison, Wisconsin, United States

Disclosure information not submitted.
GL

Glen E. Leverson, PhD

Biostatistician
University of Wisconsin School of Medicine and Public Health
Verona, Wisconsin, United States

Disclosure information not submitted.
MM

Muhammed Murtaza, MBBS, PhD

Associate Professor of Surgery
University of Wisconsin-Madison
Madison, Wisconsin, United States

Disclosure information not submitted.

Senior Author(s)

EC

Evie Carchman, MD, FACS

Associate Professor
University of Wisconsin School of Medicine and Public Health
Madison, Wisconsin, United States

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.

All of the relevant financial relationships listed below have been mitigated.

Hillary R. Johnson, MD: This individual has no financial relationships with ineligible companies.

Corinne Praska, MD: This individual has no financial relationships with ineligible companies.

Evie Carchman, MD, FACS: This individual has no financial relationships with ineligible companies.

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Purpose/Background: Little is known about which patients with anal dysplasia will progress to anal cancer. There are currently no biomarkers or screening mutations that identify patients at greater risk of progression. The most common driver mutations found in anal cancer affect the catalytic subunit of Phosphatidylinositol (3,4,5)-trisphosphate Kinase (PI3K), found in about 20% of anal cancer samples. We hypothesized that PI3K mutations would be identified in patients with precancerous lesions. In our current study, we sought to identify if these PI3K mutations were associated with specific demographic factors including risk factors for anal cancer.

Methods/Interventions: Archived tissue samples with known anal dysplasia and anal cancer were obtained through our institutional biobank. DNA was extracted and digital PCR (dPCR) assays for three of the most common PI3K mutants, E545K, H1047R, and H1047L (Qiagen dPCR LNA mutation assays), were performed. Mutation status of these samples was compared with HIV status, tobacco use history, transplantation status, history of sexually transmitted infection (STI), and histologic grade (low-grade dysplasia, high-grade dysplasia, or anal cancer) using Fisher’s exact tests. Those with unknown HIV status were excluded from this comparison.

Results/Outcomes: A total of 135 specimens from 83 unique patients were analyzed in this study. Of the 135 sequenced samples, 2 were positive for H1047L mutations; 3 were positive for H1047R mutations, and 47 were positive for E545K mutations. Five samples were positive for more than one mutation. There was no association between mutation status and tobacco use (p=0.6), history of STI (p=0.4), or transplantation history (p=0.2). However, there was an inverse association between mutation status and HIV status (p=0.002). Of those samples with mutation, 26% of patients were HIV positive. In patient samples without mutation, 63% of patients were HIV positive. Additionally, there was an association between grade of disease and mutation status (p < 0.0001) with cancer samples more likely to be positive for mutation than dysplasia samples.

Conclusion/Discussion: PI3K mutation can be detected in anal dysplasia and anal cancer in patient samples. Of the samples tested, HIV positive patients were less likely to have PI3K mutation. These PI3K mutants were also more likely to be present in anal cancer samples than in anal dysplasia samples.