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  11. The Common Expression Of Insm1 In Hpv-related Oropharyngeal Squamous Cell Carcinomas Is Not Associated With True Neuroendocrine Transformation Or Aggressive Behavior.

The Common Expression of INSM1 in HPV-related Oropharyngeal Squamous Cell Carcinomas Is Not Associated With True Neuroendocrine Transformation or Aggressive Behavior.

Swati Bhardwaj1, Brandon Veremis1, Rocco Fernandino2

  • 1Departments of Pathology, Molecular and Cell Based Medicine.

The American Journal of Surgical Pathology
|September 27, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Insulinoma-associated protein 1 (INSM1) is frequently expressed in human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC). However, INSM1 staining alone is unreliable for diagnosing neuroendocrine transformation or predicting aggressiveness in HPV-OPSCC.

Area of Science:

  • Oncology
  • Pathology
  • Biomarker Research

Background:

  • Insulinoma-associated protein 1 (INSM1) is a recognized marker for neuroendocrine (NE) differentiation.
  • High-grade NE transformation in HPV-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) is morphologically challenging to identify and indicates aggressive behavior.
  • INSM1 is proposed as a practical marker for evaluating NE differentiation in HPV-OPSCC.

Purpose of the Study:

  • To determine the incidence of INSM1 expression in HPV-OPSCC.
  • To investigate the role of INSM1 in identifying NE transformation.
  • To assess the prognostic significance of INSM1 in relation to clinical aggressiveness of HPV-OPSCC.

Main Methods:

  • Analysis of 46 nonselected HPV-OPSCC cases stained for INSM1 and synaptophysin.

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  • Retrospective staining of clinically matched aggressive (n=28) and nonaggressive (n=26) HPV-OPSCC cohorts for INSM1 and synaptophysin.
  • Statistical analysis to determine the prognostic significance of INSM1 staining.

    • Main Results:

    • INSM1 expression was detected in 42% of HPV-OPSCC cases.
    • Synaptophysin, a classical NE marker, was not co-expressed in any case.
    • INSM1 staining was significantly more frequent in nonaggressive tumors (50.0%) compared to aggressive tumors (21.4%, P=0.03).

    Conclusions:

    • INSM1 expression is common in HPV-OPSCC but not typically associated with true NE transformation.
    • INSM1 staining alone is not a reliable indicator of aggressive behavior in HPV-OPSCC.
    • Over-reliance on INSM1 for diagnosing NE differentiation in HPV-OPSCC could lead to misinterpretation and potentially detrimental clinical decisions.