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The following is a summary of “Expression patterns of HDAC6 in correlation to ARID1A status in different subtypes of endometriosis: A retrospective tissue microarray analysis,” published in the August 2024 issue of Obstetrics and Gynecology by Zingg et al.

Endometriosis, affecting approximately 10% of women of reproductive age, is associated with various genetic and molecular abnormalities. One notable genetic alteration is the loss of the tumor suppressor gene AT-rich interactive domain-containing protein 1A (ARID1A), which is present in some endometriosis cases. Histone deacetylase 6 (HDAC-6), an enzyme implicated in several diseases, including cancer and immunological disorders, plays a role in protein trafficking, degradation, and cellular functions such as shape and migration. In ovarian cancer with ARID1A deficiency, increased HDAC-6 expression has been shown to inhibit apoptosis through post-translational modification of p53. However, the impact of HDAC-6 expression in ARID1A-deficient endometriosis remains unexplored. This study investigated the correlation between HDAC-6 expression and ARID1A status in endometriotic lesions. 

Researchers analyzed two tissue microarrays comprising 168 endometriotic lesions, categorized into ovarian (38%), peritoneal (39%), and deep-infiltrating (23%) subtypes, alongside 73 endometrial samples from women without endometriosis. The mean immunoreactivity scores (IRS) for ARID1A in endometriotic lesions were 10.83 (±2.36) for epithelium and 10.78 (±1.94) for stroma, while the mean HDAC-6 IRS were 9.16 (±2.76) and 5.94 (±2.88) respectively. Notably, HDAC-6 expression was significantly higher in deep-infiltrating endometriosis compared to other subtypes, both in the epithelium (p=0.032) and stroma (p=0.007). In ARID1A-negative cases, epithelial HDAC-6 expression was elevated in endometriosis compared to controls (p=0.031), with a specific increase observed in ovarian endometriosis (p=0.037). 

No significant differences were noted in stromal HDAC-6 expression. These findings reveal a complex expression pattern of HDAC-6 that varies with ARID1A status and endometriosis subtype, suggesting a potential role in the disease’s progression. Further research is needed to understand the mechanisms by which HDAC-6 and ARID1A contribute to the malignant transformation of endometriosis.

Source: sciencedirect.com/science/article/abs/pii/S0301211524004846