(1) Background: To investigate the effect of phosphohistone H3 (PHH3) and vitamin D receptor (VDR) in the risk assessment of endometriosis, in two cohorts of women with this pathology, those receiving hormonal treatment, and those without treatment; (2) Methods: In 60 cases of women with endometriosis, the paraffin-embedded endometriosis tissue samples, retrieved after surgery, were immunohistochemically (IHC) analyzed aiming to determine the expression status of PHH3 and VDR; (3) Results: The IHC positive index of PHH3 and VDR of these two groups were compared. PHH3 levels were positively correlated with vitamin D levels, both being increased in patients without treatment. Within the group without treatment, PHH3 and VDR expressions were positively associated; (4) Conclusions: IHC analysis of PHH3 and VDR can be used as an additional tool for risk stratification and prognostic assessment in patients with endometriosis.

(1) Background: Our study aimed to examine tissue expression of CD44, vitamin D receptor (VDR), and cyclooxygenase 2 (COX-2) in endometriosis-affected women with and without progestin treatment and to inquire about their implications in the pathogenesis of endometriosis. (2) Methods: A cohort of 60 women diagnosed with endometriosis was divided into two groups, of which 26 received progestin treatment and 34 without treatment. We conducted an immunohistochemical (IHC) analysis of paraffin-embedded endometriosis tissue samples collected post endometriosis surgery. The primary goal was to elucidate VDR, COX-2, and CD44 expression patterns. (3) Results: CD44 evaluation revealed a positive score in 32 (60%) of the untreated cases, and 21 (40%) of the treated ones, but the difference didn’t reach statistical significance. VDR was observed to be higher in the group without treatment, with 32 individuals (88.9%) showing positive expression, compared to 20 individuals (83.33%) in the treatment group. Endometriotic tissue consistently demonstrated uniformly strong membrane positivity for COX-2 in all of our 60 included cases. (4) Conclusions: IHC analysis of VDR, CD44, and COX-2 are supplementary tools for risk stratification and prognostic evaluation in patients diagnosed with endometriosis. Notably, this study highlights the immunological differences between untreated and treated endometriosis.