Factors that may predict endometriosis progression to ovarian cancer

Ján Varga, PhD

The progression of endometriosis into cancer has become a topic of recent study. Ján Varga, PhD, of the department of gynecology and obstetrics in the faculty of medicine at P.J. Šafárik University and L. Pasteur University Hospital, in Košice, Slovakia, and colleagues have added to existing research by examining the factors that contribute to the process.

Researchers studied 189 patients. Sixty women with endometriosis had both PCR examination and prospective conventional cytogenetics by banding technique of the genes HIF1A (HIF1-α) and CTNNB1 (β-catenin) performed. Varga and colleagues also completed PCR examination of 50 healthy women for comparison of both genes. Seventy-nine patients had retrospective histopathological analysis completed, of which 60 patients had endometriosis and 19 patients who had endometriosis-associated ovarian cancer (EAOC).

Varga and colleagues reported that 5 patients with endometriosis had differences from normal cytogenetics without an effect on phenotype. For 6 patients with endometriosis, researchers said they did not confirm EAOC ectopic endometrium. For the last 13 cases, researchers saw either atypical or benign endometriosis, or borderline carcinoma structures.

Researchers histologically confirmed atypical endometriosis in 12 (20%) of the 60 endometriosis patients and said the determination of CTNNB1 and HIF1A gene expression created 2 subgroups. They stated that a “transcriptionally incipient endometriosis subgroup with insignificant genes expression compared to control group. In transcriptionally evident endometriosis subgroup were genes expressions significantly higher compared to control group (P < 0.01) as well as transcriptionally incipient endometriosis subgroup (P < 0.05).”¹

They concluded that structurally significant chromosome abnormalities do not affect genetic rigging in endometriosis patients. “Atypical endometriosis represents a histopathologically detectable intermediate of endometriosis progression.”1 They said CTNNB1 and HIF1A expression helps to identify at risk patients with endometriosis who would require more specific management.

In an interview with Contemporary OB/GYN®, Varga said that, for providers in practice, endometriosis must be thought of as a disease with the potential to cause cancer, even though the incidence is less than 1%. “Patients with increased risk should be under more precise observation. In clinical aspects, we have to be careful in long-term persistent ovarian endometriosis, advanced stages of endometriosis or postoperative residual disease, as well as in the presence of atypia in endometriosis histology. All these patients have increased risk for endometrioid ovarian cancer and clear cell ovarian cancer,” Varga explained.

He also described the next steps for further research. “Structural chromosomal abnormalities are not seen in these patients; thus, we have to focus on separate mutations. Advanced immunohistochemical assessment of endometriosis tissue can raise an awareness about the background and potential of endometriotic lesion,” he said. He explained that the examination of CTNNB1 and HIF1A showed promising results and more detailed studies in the future will be helpful. “In the second sequence, the histopathological criteria for atypical endometriosis should be more unified. Systematic application of these criteria at least in high-risk patients could be included in standard pathological protocol,” he told Contemporary OB/GYN®.

Varga said it was essential that providers understand that “our thinking about endometriosis should be in a broader context than just thinking about a disease leading to pain and infertility. Unusual symptomatology includes an organ-specific clinical presentation as well as potential of malignant overthrow.” He noted that several specifics can be observed in the treatment of this disease, which includes mainly surgical treatment but also infertility management. “It is necessary to centralize patients with endometriosis and offer them the best possibilities for diagnosis and treatment,” he said.

Reference

1. Varga J, Reviczká A, Háková H, Švajdler P, Rabajdová M, Ostró A. Predictive factors of endometriosis progression into ovarian cancer. J Ovarian Res. 2022;15(1):5. Published 2022 Jan 10. doi:10.1186/s13048-021-00940-8