Data from Multiplex Immunofluorescence in Formalin-Fixed Paraffin-Embedded Tumor Tissue to Identify Single-Cell–Level PI3K Pathway Activation

• DOI: 10.1158/1078-0432.c.6529616
• Publication Date: 2023-04-01T07:27:28Z
• Authors: Konrad H. Stopsack; Ying Huang; Svitlana Tyekucheva; Travis A. Gerke; Clyde Bango; Habiba Elfandy; Michaela Bowden; Kathryn L. Penney; Thomas M. Roberts; Giovanni Parmigiani; Philip W. Kantoff; Lorelei A. Mucci; Massimo Loda
• Keywords: Tissue microarray; Interquartile range; Multiplex; Quartile; Biochemical recurrence

<div>AbstractPurpose:<p>Identifying cancers with high PI3K pathway activity is critical for treatment selection and eligibility into clinical trials of inhibitors. Assessments tumor signaling need to consider intratumoral heterogeneity multiple regulatory nodes.</p>Experimental Design:<p>We established a novel, mechanistically informed approach assessing pathways by quantifying single-cell–level multiplex immunofluorescence using custom algorithms. In proof-of-concept study, we stained archival formalin-fixed, paraffin-embedded (FFPE) tissue from patients primary prostate cancer in two prospective cohort studies, the Health Professionals Follow-up Study Physicians’ Study. PTEN, stathmin, phospho-S6 were quantified on 14 microarrays as indicators activation derive cell-level scores.</p>Results:<p>In 1,001 men, 988,254 cells assessed (median, 743 per tumor; interquartile range, 290–1,377). scores higher tumors PTEN loss scored pathologist, Gleason grade, new, validated bulk transcriptional signature. Unsupervised machine-learning approaches resulted similar clustering. Within-tumor was high. During long-term follow-up 15.3 years), rates progression metastases death twice highest quartile compared lowest (hazard ratio, 2.04; 95% confidence interval, 1.13–3.68).</p>Conclusions:<p>Our novel pathway-focused FFPE identifies that are more aggressive may respond inhibitors.</p></div>