CD34 Immunoreactivity in Endometrial Stroma of Normal Endometrium and Its Alterations in Abnormal Uterine Bleeding: A comprehensive review

Abstract

Background: The endometrial stroma is composed of two immunophenotypically distinct regions—the basalis and functionalis, each exhibiting characteristic protein expression patterns fundamental to normal endometrial cycling. CD34 is a well-documented marker of basalis stromal fibroblasts, whereas the functionalis stroma demonstrates a calretinin-positive phenotype. Disruption of these stromal compartments is implicated in the development of abnormal uterine bleeding (AUB). Despite existing literature on stromal markers, a comprehensive evaluation of CD34 immunoreactivity across the spectrum of normal and abnormal endometrial conditions remains limited.

Aim: To assess CD34 immunoreactivity in the stromal compartment of normal endometrium and to evaluate alterations in CD34 expression in cases of AUB, with emphasis on dysfunctional uterine bleeding and structural causes of abnormal uterine bleeding.

Materials and Methods: This observational study examined endometrial specimens across physiological phases and AUB subtypes. CD34 immunostaining was assessed using a semi-quantitative scoring system modelled after previous studies. Patterns of stromal reactivity were compared between basalis and functionalis regions and correlated with stromal morphology and calretinin expression.

Results: Normal endometrium consistently demonstrated strong CD34 expression in basalis stromal fibroblasts, with negligible reactivity in functionalis stroma. In contrast, AUB cases exhibited marked disturbances in stromal compartmentalisation, including upward extension of CD34-positive basalis-type fibroblasts into the functionalis, loss of calretinin in affected areas, stromal–glandular asynchrony, and aberrant stromal remodelling. Structural AUB lesions demonstrated characteristic CD34 patterns, diffuse positivity in polyps, weak or absent staining in hyperplasia and malignancy, and negative staining in adenomyosis and endometriosis.

Conclusion: CD34 is a reliable marker for distinguishing normal basalis stroma from functionalis stroma. Its altered distribution in AUB reflects underlying stromal disorganisation and underscores its diagnostic value as an adjunct marker in identifying disordered endometrial stroma.