Endometrial carcinoma is the most common gynecological malignancy in developed countries and ranks as the fourth most common cancer among women worldwide. Its incidence is steadily rising, a trend attributed to the aging population and increasing rates of obesity, both known risk factors for the disease. Histopathologically, endometrial carcinoma is classified into two major types: Type I (endometrioid) and Type II (non-endometrioid), each with distinct etiological, clinical, and prognostic characteristics.[1]

Type I endometrial carcinomas are often preceded by atypical hyperplasia and are associated with excess estrogen exposure. They typically present at an early stage and have a favorable prognosis. In contrast, Type II carcinomas, which include serous and clear cell carcinomas, usually occur in atrophic endometria, are not related to estrogen stimulation, present at more advanced stages, and have a poorer prognosis.[2]

Recent advancements in molecular biology have led to a more nuanced understanding of endometrial carcinoma. Molecular profiling has revealed four distinct prognostic categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. These categories are proposed to complement traditional histopathological grading systems, offering a more comprehensive prognostic evaluation and aiding in treatment decisions.[3]

Given these complexities, the prognostic value of histopathological features in endometrial carcinoma remains a pivotal area of research. Studying these features in correlation with clinical outcomes can provide insights into the biological behavior of tumors and influence therapeutic strategies, potentially leading to personalized treatment approaches.[4]

Furthermore, the role of the tumor microenvironment, characterized by immune cell infiltration and stromal characteristics, is gaining attention for its prognostic significance. Understanding the interaction between tumor cells and their microenvironment could unveil new prognostic markers and therapeutic targets.[5]

Aim

To analyze the histopathological features of endometrial carcinoma and evaluate their prognostic value.

Objectives

1. To categorize the histopathological features of endometrial carcinoma in the study population.
2. To correlate these histopathological features with clinical outcomes to ascertain prognostic value.
3. To assess the association of tumor microenvironment characteristics with the prognosis of endometrial carcinoma.

Source of Data

The study utilized retrospective data collected from patients diagnosed with endometrial carcinoma.

Study Design

 This was a retrospective cross-sectional study.

Study Location

The study was conducted at the Pathology Department of the tertiary care hospital.

Study Duration

Data were collected from January 2022 to December 2024.

Sample Size

The study included a total of 120 patients diagnosed with endometrial carcinoma.

Inclusion Criteria

Women diagnosed with endometrial carcinoma based on histopathological evaluation, aged 18 years and older.

Exclusion Criteria

Patients with incomplete medical records, those who had received prior cancer treatment, and cases with non-epithelial tumors of the uterus.

Procedure and Methodology

Histopathological features were classified according to the latest WHO classification system. The clinical data included age at diagnosis, tumor stage, grade, and survival outcomes.

Sample Processing

All histopathological samples were fixed in 10% buffered formalin and embedded in paraffin. Slides were stained with Hematoxylin and Eosin for routine pathological evaluation and immunohistochemical analysis was performed where necessary.

Statistical Methods

Data were analyzed using SPSS version 25. Descriptive statistics were used to summarize the data. The Kaplan-Meier method was used for survival analysis, and Cox proportional hazards regression models were applied to determine the prognostic significance of histopathological features.

Data Collection

Data were collected from patient medical records and pathology reports. This included demographic data, clinical presentation, histopathological findings, treatment details, and follow-up information regarding recurrence and survival.

Table 1: Analysis of Histopathological Features and Their Prognostic Value

Table 1 presents the statistical analysis of various histopathological features and their significance in predicting the prognosis of endometrial carcinoma. The age at diagnosis has a mean of 53.7 years with a standard deviation of 11.2 years, shown to be significant with a t-test (p=0.04), indicating variation in age may correlate with different clinical outcomes. Tumor grade, particularly Grade 1, accounts for 19.2% of cases and is statistically significant (p=0.01) suggesting its prognostic relevance. Tumor stage I is observed in 56.7% of patients, with its proportion significantly associated with outcomes (p=0.03). Lymphovascular invasion is present in 37.5% of cases, and myometrial invasion of depth greater than 50% is seen in 26.7% of cases, both showing significant prognostic implications (p=0.02 and p=0.05, respectively).

Table 2: Categorization of Histopathological Features

This table categorizes the histopathological types of endometrial carcinoma observed in the study. It shows a predominant occurrence of the Endometrioid type in 70% of cases, with significant findings (p=0.01). Other types such as Serous, Clear Cell, and Mixed Type are less frequent, present in 15%, 8.3%, and 6.7% of cases, respectively, each statistically significant, highlighting the diverse histological landscape of endometrial carcinoma.

Table 3: Correlation of Histopathological Features with Clinical Outcomes

Table 3 correlates histopathological features with clinical outcomes such as overall survival, disease-free survival, and recurrence rate. The five-year overall survival rate stands at 72.5% and the disease-free survival at 65.0%, both with significant log-rank test results (p=0.001 and p=0.005, respectively), emphasizing their importance in clinical prognosis. The recurrence rate is 30%, with a significant correlation to histopathological features (p=0.03), underscoring the challenges in managing recurrent disease.

Table 4: Association of Tumor Microenvironment Characteristics with Prognosis

The final table explores the impact of tumor microenvironment characteristics on prognosis, identifying high immune cell infiltration in 36.7% of cases, dense stromal characteristics in 32.5%, and low tumor purity in 44.2%—each feature significantly associated with patient outcomes (p=0.002, p=0.003, and p=0.01, respectively). These findings suggest that the tumor microenvironment plays a critical role in the behavior and progression of endometrial carcinoma.

Table 1: Analysis of Histopathological Features and Their Prognostic Value

The findings from Table 1 show a significant correlation between various histopathological features and the prognosis of endometrial carcinoma. The average age at diagnosis was 53.7 years, which aligns with data from other studies indicating that the peak incidence of endometrial carcinoma occurs in the postmenopausal age group, highlighting age as a significant risk factor Raffone A et al.(2020)[6]. The prognostic relevance of tumor grade and stage is well-documented; early-stage and lower-grade tumors are generally associated with a better prognosis, which is consistent with our findings where Stage I and Grade 1 tumors were prevalent and associated with statistically significant outcomes Kübler K et al.(2014)[7]. The presence of lymphovascular invasion and extensive myometrial invasion are known to be associated with poorer outcomes, as they are indicators of aggressive disease behavior Kihara A et al.(2017)[8].

Table 2: Categorization of Histopathological Features

Table 2 presents a categorization of histopathological types, with a predominance of the endometrioid type, which is consistent with literature stating that about 70-80% of endometrial cancers are of the endometrioid type, known for better prognostic outcomes compared to other types like serous or clear cell carcinomas Čermáková P et al.(2014)[9]. The significant values for each histotype suggest distinct biological behaviors and prognostic implications, reaffirming the importance of histological categorization in treatment planning and prognosis estimation Santoro A et al.(2021)[10].

Table 3: Correlation of Histopathological Features with Clinical Outcomes

The overall survival and disease-free survival rates presented in Table 3 are indicative of the effectiveness of current therapeutic strategies and early detection. Studies have shown that a five-year survival rate for early-stage endometrial cancer can exceed 70%, which aligns with our findings Salama A et al.(2019)[11]. The recurrence rate of 30% for more aggressive features underscores the need for ongoing surveillance and possibly adjuvant therapy in high-risk groups Vermij L et al.(2020)[12].

Table 4: Association of Tumor Microenvironment Characteristics with Prognosis

The role of the tumor microenvironment in the prognosis of endometrial carcinoma, as shown in Table 4, is becoming increasingly recognized. High immune cell infiltration and dense stromal characteristics have been associated with both prognostic implications and potential therapeutic targets. Studies have demonstrated that a reactive stroma or significant immune cell presence can either hinder or promote tumor progression, depending on the cellular context and interactions Akhtar M et al.(2019)[13]. This dual role highlights the complexity of the tumor microenvironment and its influence on cancer behavior and patient outcomes Guan J et al.(2019)[14].

The cross-sectional study of histopathological features of endometrial carcinoma and their prognostic value has provided substantial insights into the complex interplay between clinical outcomes and the pathological characteristics of endometrial cancer. Our findings underscore the significant role of traditional histopathological factors—such as age at diagnosis, tumor grade, stage, lymphovascular invasion, and myometrial invasion—in predicting the prognosis of endometrial carcinoma.

1. Age and Clinical Outcomes: The average age at diagnosis was determined to be a crucial factor, with older age correlating significantly with prognosis, reflecting the disease's prevalence in the postmenopausal demographic and its potential aggressiveness in older patients.
2. Histopathological Types and Prognosis: The study confirmed the predominance of endometrioid carcinoma, which tends to have a better prognosis compared to more aggressive forms such as serous and clear cell carcinomas. The significant statistical values associated with each histological type illustrate their distinct biological behaviors and impacts on patient management and outcomes.
3. Tumor Grade and Stage: Early-stage and lower-grade tumors showed a better prognosis, highlighting the importance of early detection and accurate staging in the management of endometrial carcinoma. The correlation between higher stages and grades with poorer outcomes emphasizes the need for aggressive treatment strategies in advanced cases.
4. Lymphovascular and Myometrial Invasion: Both lymphovascular and significant myometrial invasion were strongly associated with poorer outcomes, suggesting these features as critical markers of aggressive disease and potential targets for adjuvant therapies.
5. Tumor Microenvironment: This study also brought to light the critical role of the tumor microenvironment, particularly immune cell infiltration and stromal characteristics, in influencing the prognosis of endometrial carcinoma. The findings suggest potential therapeutic targets within the microenvironment that could be exploited to improve clinical outcomes.

In conclusion, the prognostic assessment of endometrial carcinoma can be significantly enhanced by a detailed understanding of its histopathological features. This study provides a robust framework for tailoring treatment strategies based on specific pathological characteristics, ultimately aiming to improve survival rates and reduce recurrence in patients diagnosed with endometrial cancer. Further research is required to explore the molecular underpinnings of these histopathological features and their interactions with the tumor microenvironment to develop targeted therapies and improve patient care in clinical practice.

Limitations of Study:

1. Retrospective Nature: As a retrospective analysis, this study is inherently limited by the accuracy and completeness of historical medical records. Missing data or incomplete documentation could have influenced the accuracy of the findings, particularly concerning detailed histopathological assessments and long-term follow-up outcomes.
2. Cross-Sectional Design: The cross-sectional design provides a snapshot of data at a single point in time, which limits the ability to establish causality between histopathological features and long-term clinical outcomes. This design inherently restricts the observation of progression, recurrence, and survival over time, which are crucial for a comprehensive understanding of prognostic factors.
3. Lack of Molecular Data: This study focused primarily on traditional histopathological features without incorporating molecular or genetic data, which have been increasingly recognized for their prognostic significance in endometrial carcinoma. The integration of molecular markers could potentially provide a more nuanced understanding of prognosis and therapeutic targets.
4. Sample Size and Generalizability: Although the sample size of 120 patients is adequate for initial observations, it may not be large enough to generalize the findings across all subtypes and stages of endometrial carcinoma. Furthermore, the study population's demographic and geographic concentration may limit the applicability of the findings to broader, more diverse populations.
5. Selection Bias: Being a hospital-based study, there is an inherent selection bias as the sample may not represent all cases of endometrial carcinoma, particularly those managed outside tertiary care centers or those in different healthcare settings.
6. Lack of Control Group: The absence of a control group of patients without endometrial carcinoma limits the ability to compare histopathological features across a broader spectrum of gynecological diseases, which could help refine the specificity of prognostic markers for endometrial carcinoma specifically.
7. Statistical Limitations: The reliance on certain statistical methods and the potential for overfitting models with a relatively small sample could affect the robustness of the conclusions drawn. Moreover, the study

8. might not have adjusted for all potential confounders that could influence the outcomes, such as patient comorbidities, variations in treatment modalities, and socioeconomic factors.

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