eP163 - Frequency of PI3K Mutations in Anal Dysplasia and Cancer

Sunday, June 2, 2024

8:18 AM – 8:23 AM ET, USA

Location: Baltimore Convention Center, Room 318-320

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)

KD

Kirsten Dennison, MS

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

Disclosure information not submitted.
ED

Elise C. Dietmann, n/a

Undergraduate Research Assistant
University of Wisconsin-Madison
Madison, Wisconsin, United States

Disclosure information not submitted.
EY

Evan Yao, B.S.

Laboratory Technician
University of Wisconsin-Madison
Madison, Wisconsin, United States

Disclosure information not submitted.
LG

Laura Gunder, MS

Senior Research Specialist
University of Illinois Chicago
Chicago, Illinois, United States

Disclosure information not submitted.
EN

Everlyne Nkadori, MPH

Research services assistant director
UW Madison
Madison, Wisconsin, United States

Disclosure information not submitted.
SM

Stephanie M. McGregor, MD PhD

Associate Professor
University of Wisconsin-Madison Department of Pathology and Laboratory Medicine
Madison, Wisconsin, United States

Disclosure information not submitted.
MM

Muhammed Murtaza, MBBS, PhD

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

Disclosure information not submitted.

Senior Author(s)

EC

Evie Carchman, MD

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

Disclosure information not submitted.

Purpose/Background: The incidence and mortality of anal cancer are increasing despite improvements in HPV vaccination and anal dysplasia screening. Although anal dysplasia is thought to be a precursor lesion, we have limited ability to identify which patients with dysplasia are at highest risk for progression to anal cancer. The most common recurrent driver mutations, detected in 20% of anal cancers, affect the catalytic subunit of Phosphatidylinositol (3,4,5)-trisphosphate Kinase (PI3K). We hypothesize that PI3K mutations are an early event in anal carcinogenesis that may help identify patients with anal dysplasia at highest risk of developing cancer. In the current study, we evaluated the frequency of PI3K mutations in anal dysplasia and cancer samples.Methods/Interventions: Archived tissue samples with known anal dysplasia and anal cancer were obtained through our institutional biobank. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) slides using the QIAamp DNA FFPE Advanced Tissue kit. Digital PCR (dPCR) assays for three of the most common PI3K mutants, E545K, H1047R, and H1047L (Qiagen dPCR LNA mutation assays), were utilized to test each sample with 20ng of template DNA on the QIAcuity microfluidic dPCR system. After correcting for loading concentration, the dPCR results are reported as total valid partitions and positive partitions (positive for wild-type and mutated DNA). Taking into account assay background, we required greater than or equal to 10 positive partitions for a sample to be considered positive for mutation.Results/Outcomes: We have analyzed 88 samples so far in this study and unblinded them for data analysis. We found 10 patient samples (11.4%) positive for E545K mutation. No H1047R or H1047L mutants were detected. Across the different stages of carcinogenesis, E545K mutation was detected in one patient (1/32, 3.1%) with pathologic low-grade dysplasia, six patients (6/52, 11.5%) with high-grade dysplasia, and three patients (3/4, 75%) with anal cancer.Conclusion/

Discussion: Our results demonstrate that PI3K mutations can be detected in a fraction of patients with anal dysplasia, with increasing frequency of mutations in later stages of anal carcinogenesis. Further research is needed to determine if patients with anal dysplasia and associated PI3K mutations may be at an increased risk of progression to anal cancer.