Background: Endometriosis-associated ovarian cancer (EAOC) arises from the malignant transformation of endometriotic lesions within the ovary. Understanding the histopathological determinants of this transformation is vital for early detection and stratification of cancer risk. While the malignant potential of endometriosis has been widely studied, the relationships among clinical factors, tumor markers, ultrasonographic morphology, genetic mutations, and EAOC risk remain insufficiently characterized.

Objective: This study evaluates the risk of endometriosis-associated ovarian cancer (EAOC) and analyze the influence of clinical characteristics, tumour biomarkers, ultrasonographic morphology, histopathological features, and mutations of ARID1A, BRAF, and p53 genes.

Methods: This study was conducted as an analytical observational study with a cross-sectional design using consecutive sampling. The independent variables comprised clinical and histopathological parameters, including patient history, physical examination findings, CA-125 levels, ultrasonographic characteristics, and genetic alterations involving ARID1A, BRAF, and p53. The study included 61 patients who underwent surgical management for endometriosis and ovarian cancer at Dr. Moewardi General Hospital, Sebelas Maret University, Surakarta. Data are analyzed by IBM SPSS 25 statistically.

Result: A total of 61 patients with clinically diagnosed endometriosis and ovarian cancer were included (n = 41 and n = 20, respectively). The overall mean age was 42.02 years, with patients in the endometriosis group having a mean age of 37 years, compared to 52.3 years in the EAOC group. No significant differences were observed in clinical history or physical examination findings, including weight loss and palpable abdominal masses (p > 0.05); however, the presence of an abdominal mass on physical examination was associated with a 1.68-fold increased risk of EAOC (PR = 1.68). In contrast, significant associations were identified between abdominal pain, ultrasonographic findings, and tumor marker levels with the risk of malignant progression (p < 0.05). The CA-125 level demonstrated a correlation coefficient of −0.181, indicating a direct relationship with the occurrence of EAOC. A significant difference (p < 0.001) in the expression of ARID1A, BRAF, and p53 genes was observed across different histopathological types of endometriosis and ovarian cancer.

Conclusion: Abdominal pain, sonographic morphology, and CA-125 levels are parameters that correlate with an increased risk of malignant transformation of endometriosis. Genetic mutations of ARID1A, BRAF, and p53 associated with the histopathological features of atypical endometriosis should be evaluated to assess their correlation with the risk of malignant transformation to endometriosis-associated ovarian cancer (EAOC). Comprehensive clinical assessment of endometriosis is essential to identify patients at increased risk for progression to EAOC.

Keywords: ARID1A, BRAF, p53,Ca 125, USG, Endometriosis, Endometriosis-associated ovarian cancer.

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