Localized immunohistochemical marker differences between cesarean scar niche and adjacent endometrium: a retrospective paired study

Abstract

Cesarean scar niche (CSN) is associated with abnormal uterine bleeding after cesarean delivery, but tissue-level differences at the scar-endometrial interface remain poorly defined. We compared CSN tissue with adjacent endometrium from the same uterus, treating the latter as an internal anatomical comparator rather than disease-free control tissue. This retrospective paired study included 44 surgically treated patients with CSN and 44 paired specimen sets (88 specimens) obtained during clinically indicated surgery between June 2020 and April 2022. Adjacent endometrium was defined as endometrial tissue immediately outside the hysteroscopically visible niche margin and was used only as an internal anatomical comparator. Seventeen immunohistochemical markers were scored on a four-level ordinal scale (0–3). The primary analysis compared lesion and adjacent-endometrial scores using two-sided Wilcoxon signed-rank tests with Benjamini-Hochberg false discovery rate (FDR) adjustment. Clinical and ultrasound analyses were secondary or exploratory and used complete cases. Fourteen of 17 markers differed between CSN tissue and adjacent endometrium after FDR adjustment. The largest lesion-enriched shifts involved inflammation-associated, vascular/growth-factor-associated, hypoxia-associated, and matrix-remodeling markers. Progesterone receptor reached FDR significance despite a median paired difference of 0 and was interpreted cautiously. No exploratory clinicopathological correlation remained significant after FDR correction. Retrospectively recorded binary symptom-improvement status was available for all 44 patients, whereas recorded postoperative bleeding/symptom duration was available for 39 complete pairs within the 40-patient bleeding-duration analysis subset and paired 3-month residual myometrial thickness for 14 patients. CSN tissue differed locally from adjacent endometrium across multiple immunohistochemical markers. Without disease-free or asymptomatic controls, molecular validation, or an independent cohort, these paired observations cannot establish disease-specific pathway activation, causality, or biomarker prediction. Prospective controlled studies should use standardized sampling and outcome assessment.