Jiří Presl

The influence of selected immunohistochemical and clinical-pathological markers on the prognosis of patients with malignant uterine tumors

Introduction: Endometrial carcinoma is the most common gynecological malignancy in developed countries, and its incidence has been increasing in recent decades. The prognosis of patients depends on a combination of clinical-pathological characteristics, and more recently, molecular indicators. The aim of this study was to analyze the influence of the selected prognostic markers – immunohistochemical (L1CAM, ER, PR) and classical (FIGO stage, grade, myometrial invasion, lymph node involvement, distant metastases) – on the survival of patients with endometrial carcinoma. Materials and methods: A retrospective evaluation was performed on 143 women with histologically confirmed endometrial cancer treated between 2014 and 2018. All patients underwent primary surgical treatment. Resected specimens were subjected to immunohistochemical analysis of L1CAM, ER, and PR. Data were statistically processed using a Kaplan-Meier analysis and the Cox proportional hazards model, adjusted to age. Results: L1CAM expression was detected in 14% of patients and was associated with shortened survival (HR ≈ 3.9). ER and PR positivity (89% and 85%, resp.) correlated with a more favorable prognosis (HR for ER positivity 0.21; PR 0.23). Classical factors such as higher grade, advanced FIGO stage, cervical and lymphovascular invasion, or presence in nodes were statistically associated with worse survival. An interesting finding was a significantly better prognosis in asymptomatic patients – the presence of symptoms increased the risk of death up to fourfold. Conclusion: L1CAM positivity and loss of hormone receptors are significant adverse prognostic factors. Their inclusion in routine immunohistochemical panel testing improves risk stratification and treatment personalization, which at the time of publication of this paper is already included in the updated ESGO-ESTRO-ESP 2025 guidelines. At the same time, it has been shown that the absence of symptoms at diagnosis is a favorable survival indicator. The results support further research into prognostic markers and their integration into clinical decision-making algorithms. Key words: endometrial carcinoma – L1 cell adhesion molecule – estrogen receptors – progesterone receptors – survival – symptoms

Advantages of next-generation sequencing (NGS) in the molecular classification of endometrial carcinomas – our experience with 270 cases

Molecular classification of endometrial carcinomas (EC) divides these neoplasms into four distinct subgroups defined by a molecular background. Given its proven clinical significance, genetic examination is becoming an integral component of the diagnostic procedure. Recommended diagnostic algorithms comprise molecular genetic testing of the POLE gene, whereas the remaining parameters are examined solely by immunohistochemistry. The aim of this study is to share our experiences with the molecular classification of EC, which has been conducted using immunohistochemistry and next-generation sequencing (NGS) at our department. This study includes all cases of EC diagnosed at Šikl's Department of Pathology and Biopticka Laboratory Ltd. from 2020 to the present. All ECs were prospectively examined by immunohistochemistry (MMR, p53), fol lowed by NGS examination using a customized Gyncore panel (including genes POLE, POLD1, MSH2, MSH6, MLH1, PMS2, TP53, PTEN, ARID1A, PIK3CA, PIK3R1, CTNNB1, KRAS, NRAS, BRCA1, BRCA2, BCOR, ERBB2), based on which the ECs were classified into four molecularly distinct groups [POLE mutated EC (type 1), hypermutated (MMR deficient, type 2), EC with no specific molecular profile (type 3), and TP53 mutated ("copy number high", type 4)]. The cohort comprised a total of 270 molecularly classified ECs. Eighteen cases (6.6%) were classified as POLE mutated EC, 85 cases (31.5%) as hypermutated EC (MMR deficient), 137 cases (50.7%) as EC of no specific molecular profile, and 30 cases (11.1%) as TP53 mutated EC. Twelve cases (4.4%) were classified as "multiple classifier" endometrial carcinoma. ECs of no specific molecular profile showed multiple genetic alterations, with the most common mutations being PTEN (44% within the group of NSMP), fol lowed by PIK3CA (30%), ARID1A (21%), and KRAS (9%). In comparison with recommended diagnostic algorithms, NGS provides a more reliable classification of EC into particular molecular subgroups. Furthermore, NGS reveals the complex molecular genetic background in individual ECs, which is especially significant within ECs with no specific molecular profile. These data can serve as a springboard for the research of therapeutic programs committed to targeted therapy in this type of tumor.