Utility of Morphologic Risk Stratification Modeling and Immunohistochemical Surrogates for Key Molecular Alterations...

Area of Science:

• Gynecologic Pathology
• Oncology
• Molecular Pathology

Background:

• Accurate diagnosis and prognostic stratification of uterine leiomyosarcoma (LMS) are crucial for effective clinical management.
• Recent studies proposed a 7-marker immunohistochemistry (IHC) diagnostic panel and a morphologic risk stratification schema.

Purpose of the Study:

• To validate the diagnostic utility of a 7-marker surrogate IHC panel for LMS.
• To assess the prognostic value of morphologic risk stratification in LMS.

Main Methods:

• Retrospective review of 34 LMS cases diagnosed between 2016-2022.
• Application of a 7-marker IHC panel (TP53, RB1, ATRX, PTEN, DAXX, MTAP, MDM2).
• Analysis of associations between molecular alterations, morphologic features, and patient survival.

Main Results:

• Abnormal IHC staining was detected in a high percentage of cases (e.g., RB1: 65%, TP53: 62%).
• The IHC panel confirmed LMS diagnosis in 79% of cases; however, 21% showed limited abnormalities, potentially causing diagnostic challenges.
• Morphologic risk stratification significantly differentiated low-, intermediate-, and high-risk groups regarding disease-specific survival (P = 0.030).
• Molecular alterations did not predict survival, but morphologic criteria provided robust prognostic stratification.

Conclusions:

• The IHC-based diagnostic panel is sensitive for confirming most LMS diagnoses.
• A subset of LMS cases with ambiguous features may benefit from additional genomic testing.
• Established morphologic criteria offer reliable prognostic stratification for uterine leiomyosarcoma.