PRAME Expression in HPV-associated and Differentiated Vulvar Intraepithelial Neoplasia-associated Vulvar Squamous

Eyas Alzayadneh1, Sarah E Gradecki2, Landon K Hobbs3

  • 1Department of Pathology, University of Virginia, Charlottesville, Virginia.

Insights

Preferentially expressed antigen in melanoma (PRAME) is found in vulvar squamous lesions. Higher PRAME expression in differentiated vulvar intraepithelial neoplasia (dVIN)-associated cancers suggests potential for targeted therapies.

Area of Science:

  • Gynecologic Oncology
  • Immunohistochemistry
  • Molecular Pathology

Background:

  • Preferentially expressed antigen in melanoma (PRAME) is a protein repressor of retinoic acid signaling with potential in cancer diagnostics and therapy.
  • PRAME's selective tumor expression and role in immunotherapy trials make it a target of interest across malignancies.
  • Vulvar intraepithelial neoplasia (VIN) and vulvar squamous cell carcinoma (VSCC) are conditions where PRAME assessment could inform treatment, especially given the disfigurement from extensive lesions.

Purpose of the Study:

  • To evaluate PRAME expression in human papillomavirus (HPV)-associated and differentiated vulvar intraepithelial neoplasia (dVIN)-associated squamous lesions.
  • To determine if PRAME expression levels differ between HPV-associated and dVIN-associated vulvar neoplasms.
  • To explore the potential of PRAME as a biomarker and therapeutic target in vulvar cancer.

Main Methods:

  • Immunohistochemistry was used to stain PRAME in 106 vulvar squamous neoplasms, including HSIL, VSCC arising in HSIL, dVIN, and VSCC arising in dVIN.
  • PRAME expression was quantified by the percentage of positive tumor cells, staining intensity (0-3+), and localization, with an H-score calculated.
  • Statistical analysis using Wilcoxon rank-sum or Kruskal-Wallis tests compared PRAME expression across different lesion types.

Main Results:

  • PRAME was expressed in most VSCCs (78%), with significantly higher expression observed in dVIN-associated lesions compared to HPV-associated lesions (P=0.006).
  • The highest PRAME expression was found in dVIN-associated VSCC, while the lowest expression was observed in HSIL (P<0.00001).
  • Distinct biological drivers in HPV-associated and dVIN-associated vulvar neoplasia appear to influence differential PRAME expression.

Conclusions:

  • Differential PRAME expression in vulvar squamous lesions correlates with distinct etiological pathways (HPV vs. dVIN).
  • The strong PRAME expression in dVIN-associated VSCC suggests a link to aggressive tumor behavior and highlights its potential as a therapeutic target.
  • dVIN-associated vulvar lesions show promise for PRAME-targeted therapies, potentially offering new treatment avenues for advanced vulvar cancer.

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