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. 2024 Sep 21;16(18):3221.
doi: 10.3390/cancers16183221.

Low-Risk and High-Risk NSMPs: A Prognostic Subclassification of No Specific Molecular Profile Subtype of Endometrial Carcinomas

Matteo Marchetti  1 , Giulia Spagnol  1 , Tommaso Vezzaro  1 , Sofia Bigardi  1 , Orazio De Tommasi  1 , Emma Facchetti  1 , Marta Tripepi  1 , Diletta Costeniero  1 , Chiara Munerol  1 , Tiziano Maggino  1 , Donato D'Antona  1 , Roberto Tozzi  1 , Carlo Saccardi  1 , Marco Noventa  1
Affiliations

Low-Risk and High-Risk NSMPs: A Prognostic Subclassification of No Specific Molecular Profile Subtype of Endometrial Carcinomas

Matteo Marchetti et al. Cancers (Basel). .

Abstract

(1) Background: Endometrial carcinoma (EC) classified as no specific molecular profile (NSMP) represents a heterogeneous group with variable prognoses. This retrospective, single-center study aims to further stratify NSMP ECs to tailor treatment strategies and improve outcomes. (2) Methods: From 2020 to 2023, we collected data on 51 patients diagnosed with NSMP EC following the introduction of molecular profiling at our institution. Patients were retrospectively analyzed for estrogen receptor (ER) status, histotype, and grade to identify potential prognostic subgroups. (3) Results: Our analysis identified two distinct subgroups within NSMP EC: low-risk and high-risk, based on ER status, histotype, and grade. The low-risk NSMP group demonstrated significantly better survival outcomes compared to the high-risk group. With a median follow-up time of 16 moths (IQR 13.0-29.7), the disease-free survival (DFS) and overall survival (OS) for the low-risk group were 100%. For the high-risk group, the DFS and OS were 71.4% and 78.6%, respectively, which showed a statistically significantly difference (Log-Rank Mantel-Cox < 0.001). In the high-risk group, four patients experienced recurrence, and three of these patients died. (4) Conclusions: Stratifying NSMP EC into low-risk and high-risk categories based on ER status, histotype, and grade can lead to more accurate prognostic assessments. In time, it may require tailored adjuvant therapies and a personalized treatment.

Keywords: NSMP; endometrial cancer; estrogen receptor; molecular classification; no specific molecular profile; prognosis; risk class.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart showing the application of exclusion criteria to arrive at the study cohort (51 NSMPs).
Figure 2
Figure 2
Oncoplot summarizing clinicopathological and immunohistochemical features, and risk classification of NSMP ECs cohort. LR, low-risk NSMP; HR, high-risk NSMP; ER, estrogen receptor; PR, progesterone receptor; ESMO, European Society of Medical Oncology.
Figure 3
Figure 3
Kaplan–Meier curves showing disease-free survival (PFS) and overall survival (OS) from the timepoint of primary surgery stratified by (A) ER status, (B) division into risk groups, (C) FIGO stage 2009. ER, estrogen receptor; NSMP, no specific molecule profile.
Figure 4
Figure 4
Diagnostic algorithm for the management of ECs: Based on the validated molecular classification, we define two risk groups obtained from NSMP ECs with completely different risks of recurrence and prognosis. The blue box presents a hypothetical future prospective derived from this study, leading to a molecular subclassification of LR-NSMP into very low-risk and intermediate-risk NSMPs. EC, endometrial carcinoma; dMMR, mismatch repair-deficient; NSMP, no specific molecular profile; POLEmut, POLE (DNA Polymerase Epsilon)-mutated/ultramutated; p53abn, p53-abnormal; HP, histopathological; EBRT, external beam radiation therapy; CT, chemotherapy.
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