Inflammatory markers and the systemic immune-inflammation index in endometrial carcinoma and hyperplasia: a retrospective cohort study.
NLR, SII, and PDW show some association with endometrial carcinoma but do not reliably distinguish it from premalignant conditions, indicating the need for histopathological evaluation.
Where it sits
this study against the rest of the mgf (mechano growth factor) corpusSummary and findings
This study evaluated the association of haematological inflammatory markers with endometrial carcinoma (EC) in a cohort of 238 patients. Significant associations were found for neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and platelet distribution width (PDW) when comparing EC patients to controls. However, these markers did not independently distinguish EC from endometrial hyperplasia (EH).
Abstract
<h4>Background</h4>Endometrial carcinoma (EC) presents commonly with abnormal uterine bleeding, and definitive diagnosis requires invasive endometrial biopsy. Haematological inflammatory markers-including the neutrophil-to-lymphocyte ratio (NLR), platelet distribution width (PDW), and the systemic immune-inflammation index (SII)-have been proposed as adjuncts in the differential diagnosis of endometrial pathologies. We evaluated whether these markers can independently discriminate EC from endometrial hyperplasia with atypia/endometrial intraepithelial neoplasia (EHA/EIN), endometrial hyperplasia without atypia (EH), and normal endometrium, after adjustment for age and other confounders.<h4>Methods</h4>Data from 238 patients who underwent endometrial biopsy for abnormal uterine bleeding between 2015 and 2020 were retrospectively analysed. Patients were categorised as EC (<i>n</i> = 74), EHA/EIN (<i>n</i> = 28), EH without atypia (<i>n</i> = 66), and controls with normal endometrium (<i>n</i> = 70). Haematological parameters, NLR, platelet-to-lymphocyte ratio (PLR), and SII were derived from preoperative complete blood count results. Univariable comparisons used the Kruskal-Wallis test with Dunn's post-hoc pairwise comparisons. Hierarchical multivariable logistic regression models were fitted, adjusting sequentially for age, menopausal status, and (where available) diabetes mellitus and hypertension. Receiver operating characteristic (ROC) analysis was performed for markers showing significant univariable discrimination, and PDW was analysed in inverted form (1-PDW direction) to reflect its inverse association with malignancy.<h4>Results</h4>NLR and SII were significantly elevated, and PDW was significantly reduced, in EC patients compared with controls (all <i>p</i> < 0.05). After adjustment for age and menopausal status, NLR (adjusted OR [aOR] 2.06, 95% CI 1.04-4.09; <i>p</i> = 0.037), SII per 100 units (aOR 1.49, 95% CI 1.09-2.04; <i>p</i> = 0.014) and PDW (aOR 0.93, 95% CI 0.89-0.96; <i>p</i> < 0.001) remained independently associated with EC versus controls. By contrast, after adjustment for age, NLR and SII no longer independently discriminated EC from EH (NLR aOR 1.27, <i>p</i> = 0.245; SII aOR 1.14, <i>p</i> = 0.165), suggesting that age accounts for a substantial proportion of the apparent univariable differences. In ROC analysis with PDW values inverted, AUCs were 0.79 (95% CI 0.72-0.87) for PDW, 0.68 (95% CI 0.59-0.76) for NLR, and 0.62 (95% CI 0.52-0.70) for SII against the control group. No marker-adjusted or unadjusted-significantly distinguished EC from EHA/EIN.<h4>Conclusions</h4>NLR, SII, and (low) PDW are independently associated with EC compared with normal endometrium, even after age and menopausal status adjustment, but their performance is modest and they do not independently discriminate EC from premalignant endometrial lesions. Histopathological evaluation remains indispensable. These markers may inform risk stratification but are not sufficient as standalone tests.
Background
This paper addresses the potential role of haematological inflammatory markers as adjuncts in the differential diagnosis of endometrial carcinoma (EC) and other endometrial pathologies. Prior studies have suggested that markers like NLR, SII, and PDW may help in distinguishing between different endometrial conditions. This study is significant as it evaluates these markers in a retrospective cohort to determine their diagnostic utility.
Methods
The study analyzed data from 238 patients who underwent endometrial biopsy for abnormal uterine bleeding from 2015 to 2020. Patients were categorized into four groups: EC (n=74), endometrial hyperplasia with atypia/endometrial intraepithelial neoplasia (EHA/EIN, n=28), endometrial hyperplasia without atypia (EH, n=66), and controls with normal endometrium (n=70). The study utilized univariable comparisons and multivariable logistic regression models to analyze the data.
Results
NLR and SII were significantly elevated, and PDW was significantly reduced in EC patients compared to controls, all with p-values less than 0.05. After adjusting for age and menopausal status, NLR had an adjusted odds ratio of 2.06 (95% CI 1.04-4.09, p=0.037) and SII per 100 units had an adjusted odds ratio of 1.49 (95% CI 1.09-2.04, p=0.014). The area under the curve for PDW was 0.79 (95% CI 0.72-0.87).
Interpretation
The findings suggest that while NLR, SII, and PDW are associated with EC compared to normal endometrium, their ability to independently discriminate EC from premalignant lesions is limited. The modest performance of these markers indicates that they may not be clinically meaningful in practice without further histopathological evaluation. Additionally, the influence of age on the results highlights a potential confounder that should be considered in clinical assessments.
Key findings
- NLR significantly elevated in EC patients compared with controls, p<0.05.
- SII significantly elevated in EC patients compared with controls, p<0.05.
- PDW significantly reduced in EC patients compared with controls, p<0.05.
- Adjusted odds ratio for NLR in EC versus controls was 2.06, 95% CI 1.04-4.09, p=0.037.
- Adjusted odds ratio for SII per 100 units in EC versus controls was 1.49, 95% CI 1.09-2.04, p=0.014.
- Area under the curve for PDW was 0.79, 95% CI 0.72-0.87.
Limitations
- Retrospective cohort study design.
- Small sample size for some groups.
- Modest performance of the markers.
- Age as a significant confounder.
- No independent discrimination of EC from EHA/EIN.