Histopathological and Immunohistochemical Prognostic Factors in High-Grade Non-Endometrioid Carcinomas of the Endometrium (HG-NECs): Is It Possible to Identify Subgroups at Increased Risk?

Michele Paudice; Chiara Maria Biatta; Giulia Scaglione; Alessia Parodi; Serafina Mammoliti; Melita Moioli; Maria Grazia Centurioni; Fabio Barra; Simone Ferrero; Franco De Cian; Katia Mazzocco; Valerio Gaetano Vellone

doi:10.3390/diagnostics13132171

Histopathological and Immunohistochemical Prognostic Factors in High-Grade Non-Endometrioid Carcinomas of the Endometrium (HG-NECs): Is It Possible to Identify Subgroups at Increased Risk?

Diagnostics (Basel). 2023 Jun 26;13(13):2171. doi: 10.3390/diagnostics13132171.

Authors

Michele Paudice^{1

2}, Chiara Maria Biatta³, Giulia Scaglione⁴, Alessia Parodi¹, Serafina Mammoliti⁵, Melita Moioli⁶, Maria Grazia Centurioni⁷, Fabio Barra⁸, Simone Ferrero^{6

9}, Franco De Cian^{1

10}, Katia Mazzocco¹¹, Valerio Gaetano Vellone^{1

11}

Affiliations

¹ Department of Integrated Diagnostic and Surgical Sciences (DISC), University of Genoa, 16100 Genoa, Italy.
² Pathology University Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
³ Anatomy and Pathological Histology, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy.
⁴ Pathology Unit, Fondazione Policlinico A. Gemelli IRCCS, 00168 Rome, Italy.
⁵ Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
⁶ Obstetrics & Gynecology University Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
⁷ Obstetrics & Gynecology, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
⁸ Department of Health Sciences (DISSAL), University of Genoa, 16132 Genoa, Italy.
⁹ Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, 16132 Genoa, Italy.
¹⁰ General Surgery University Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
¹¹ Pathology Unit, IRCCS Istituto Giannina Gaslini, 16132 Genoa, Italy.

Abstract

Endometrial cancer is an emerging disease with an increase in prevalence of aggressive histotypes in recent years.

Background: In the present study, potential histopathological and immunohistochemical prognostic markers were investigated. Consecutive cases of high-grade non-endometrioid carcinoma (HG-NEC) of the endometrium were considered.

Methods: Each surgical specimen was routinely processed; the most significant block was selected for immunohistochemistry and tested for ER, PR, ki67, p53, E-cadherin, β-catenin, Bcl-2 and cyclin D1. For each immunomarker, the percentage of positive tumor cells was evaluated (%) and dichotomized as low and high according to the distribution in the study population. Follow-up was collected for disease-free survival (DFS) and overall survival (OS). Thirty-three cases were eligible: 19 resulted in FIGO I-II; 14 resulted in FIGO III-IV. Twelve patients suffered a recurrent disease (mean follow-up 24.6 months); 8 patients died of the disease (mean follow-up 26.6 months).

Results: Women with recurrent disease demonstrated a significantly higher Bcl2% (35.84 ± 30.96% vs. 8.09 ± 11.56%; p = 0.0032) while DOD patients had higher ki67% (75 ± 13.09% vs. 58.6 ± 19.97%; p = 0.033) and Bcl2% of border significance (34.37 ± 34.99% vs. 13 ± 17.97%; p = 0.078). As expected, FIGO III-IV had a worse DFS (HR = 3.34; 95% CI: 1.1-10.99; p = 0.034) and OS (HR = 5.19; 95% CI: 1.27-21.14; p = 0.0217). Bcl-2-high patients (Bcl2 > 10%) demonstrated a significantly worse DFS (HR = 9.11; 95% CI: 2.6-32.4; p = 0.0006) and OS (HR = 7.63; 95% CI: 1.7-34; p = 0.0084); moreover, PR low patients (PR ≤ 10%) had significantly worse DFS (HR = 3.74; 95% CI: 1.2-11.9; p = 0.02).

Conclusions: HG-NEC represents a heterogeneous group of endometrial aggressive neoplasms with a worrisome prognosis, often at an advanced stage at presentation. Bcl-2 and PR may represent promising markers to identify a subgroup of patients having an even worse prognosis requiring a careful and close follow-up.

Keywords: endometrial carcinoma; immunohistochemistry; prognosis.

Grants and funding

This paper was funded by Lega Italiana per la Lotta contro i Tumori-LILT-Bando 5 × 1000 anno 2019.