Molecular Classification Outperforms Histologic Classification in Prognostication of High-grade Endometrial Carcinomas With Undifferentiated and Sarcomatous Components

The American Journal of Surgical Pathology, vol. 48, pp. 953–964

Abstract

Since the establishment of 4 molecular subgroups of endometrial carcinoma (EC), there has been significant interest in understanding molecular classification in the context of histologic features and diagnoses. ECs with undifferentiated, spindle, and/or sarcomatous components represent a diagnostically challenging subset of tumors with overlapping clinical and histologic features. We examined the clinicopathologic, morphologic, immunohistochemical, and molecular features of these tumors identified in our institutions' pathology databases using immunohistochemistry and targeted sequencing. Disease-specific survival (DSS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves and log-rank tests. One hundred sixty-two ECs were included: carcinosarcomas (UCS; n=96), dedifferentiated/undifferentiated EC (DDEC/UDEC; n=49), and grade 3 endometrioid EC with spindled growth (GR3spEEC) (n=17). All molecular subgroups were represented in all histologic subtypes and included 12 (7%) POLE -mutated ( POLE mut), 43 (27%) mismatch repair-deficient (MMRd), 77 (48%) p53-abnormal (p53abn), and 30 (19%) no specific molecular profile (NSMP) tumors. However, the molecular classification (irrespective of histologic diagnosis) was a significant predictor for both DSS ( P =0.008) and P≤0.0001). POLE mut EC showed an excellent prognosis with no recurrences or deaths from the disease. MMRd tumors also showed better outcomes relative to NSMP and p53abn tumors. In conclusion, molecular classification provides better prognostic information than histologic diagnosis for high-grade EC with undifferentiated and sarcomatous components. Our study strongly supports routine molecular classification of these tumors, with emphasis on molecular group, rather than histologic subtyping, in providing prognostication.

Authors 15

1. Phoebe M. Hammer corresponding

   Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Pathology, Stanford University School of Medicine, Stanford, CA

2. Aihui Wang corresponding

   Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Pathology, Stanford University School of Medicine, Stanford, CA

3. Lisa Vermij Aachen Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands

4. Sabrina Zdravkovic corresponding

   Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Pathology, Stanford University School of Medicine, Stanford, CA

5. Lucas Miecho Heilbroner corresponding

   Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Pathology, Stanford University School of Medicine, Stanford, CA

6. Emily Elizabeth Ryan corresponding

   Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Pathology, Stanford University School of Medicine, Stanford, CA

7. Rachel L P Geisick corresponding

   Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Pathology, Stanford University School of Medicine, Stanford, CA

8. Vivek Charu corresponding

   Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Pathology, Stanford University School of Medicine, Stanford, CA

9. Teri A. Longacre corresponding

   Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Pathology, Stanford University School of Medicine, Stanford, CA

10. Carlos J. Suarez corresponding

    Stanford Medicine · Stanford University

    Affiliation as printed

    Department of Pathology, Stanford University School of Medicine, Stanford, CA

11. Chandler C. Ho corresponding

    Stanford Medicine · Stanford University

    Affiliation as printed

    Department of Pathology, Stanford University School of Medicine, Stanford, CA

12. Taylor M. Jenkins

    Virginia Commonwealth University · Virginia Commonwealth University Medical Center

    Affiliation as printed

    Department of Pathology, Virginia Commonwealth University Health System, Richmond

13. Anne M. Mills

    University of Virginia Health System

    Affiliation as printed

    Department of Pathology, University of Virginia Health System, Charlottesville, VA

14. Tjalling Bosse Aachen Department of Pathology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands

15. Brooke E. Howitt corresponding

    Stanford Medicine · Stanford University

    Affiliation as printed

    Department of Pathology, Stanford University School of Medicine, Stanford, CA