Expression patterns of HDAC6 in correlation to ARID1A status in different subtypes of endometriosis: A retrospective tissue microarray analysis

• Published in: European journal of obstetrics & gynecology and reproductive biology 2024-11, Vol.302, p.73-80
• Main Authors: Zingg, Joelle, Kalaitzopoulos, Dimitrios R., Karol, Agnieszka A., Samartzis, Nicolas, Stancl, Paula, Hutmacher, Juliane, Karlic, Rosa, Noske, Aurelia, Choschzick, Mathias, Witzel, Isabell, Samartzis, Eleftherios P.
• Format: Article
• Language: English
• Subjects: ARID1A; Endometriosis; HDAC6; Tissue microarray
• ISSN: 0301-2115; 1872-7654; 1872-7654
• DOI: 10.1016/j.ejogrb.2024.08.044

•HDAC6 expression was higher in endometriotic lesions of deep-infiltrating endometriosis, in both, epithelium and stroma, compared to the other endometriosis subtypes.•In ARID1A negative cases, epithelial expression of HDAC6 was higher in endometriotic lesions compared to eutopic endometrium of women without endometriosis.•There were no significant differences in the stromal expression of HDAC6. Endometriosis is a disease affecting approximately 10% of reproductive age women. Loss of the tumor suppressor gene AT-rich interactive domain-containing protein 1A (ARID1A) occurs in some endometriosis cases. Histone deacetylase 6 (HDAC-6) is an enzyme with implication in several diseases including different cancer types and immunological disorders, where it is involved in protein trafficking and degradation, cell shape, and migration. In ARID1A-deficient ovarian cancer increased HDAC-6 expression lead to apoptosis-inhibiting post-translational modification of p53. It is not known if HDAC-6 expression is also altered in ARID1A-deficient endometriosis. The aim of this study was to assess HDAC-6 expression in endometriotic lesions in correlation to ARID1A-status. Two tissue-microarrays with 168 endometriotic lesions, including ovarian (64/168, 38 %), peritoneal (66/168, 39 %) and deep-infiltrating (38/168, 23 %) subtypes, and 73 endometrium of women without endometriosis were assessed. Mean ARID1A immunoreactivity score (IRS) in endometriosis group was 10.83 (±2.36) and 10.78 (±1.94) in the epithelium and stroma, respectively, while the respective mean HDAC6 IRS were 9.16 (±2.76) and 5.94 (±2.88). The comparison of the HDAC6 expression between endometriosis subtypes showed higher expression in deep-infiltrating endometriosis, in both, epithelium (p = 0.032) and stroma (p = 0.007). In ARID1A negative cases, epithelial expression of HDAC6 was higher in endometriosis compared to women without endometriosis (p = 0.031), and this was also specifically observed in the subset of ovarian endometriosis (p = 0.037). There were no significant differences in the stromal expression of HDAC6. In conclusion, our results demonstrate a complex expression pattern of HDAC6 depending on ARID1A status in different endometriosis subtypes. Further studies on HDAC6 and ARID1A are important to elucidate mechanisms involved in malignant transformation of endometriosis.