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Yet another study has demonstrated a link between severe obesity and occult endometrial cancer (EC), or risk factors for it, in women undergoing bariatric surgery.

Among 72 women with class III-IV obesity, endometrial biopsies displayed neoplastic changes in 10 at baseline, while four women had EC and six others had atypical hyperplasia (AH), reported Emma Crosbie, MD, of the University of Manchester in England, and colleagues.

Moreover, significant weight loss precipitated by that surgery was shown to substantially attenuate that risk and normalize endometrial pathology, they wrote in the .

Crosbie's group said that for type 1 EC and its precursor AH, the strongest risk factor is obesity, noting that each 5 kg/m² body mass index (BMI) increase confers a 1.6-fold higher EC risk.

"We found an unexpectedly high prevalence of occult neoplastic changes in the endometrium of women undergoing bariatric surgery," they wrote. "And not only is weight loss associated with resolution of AH, but the molecular changes that ensue even in morphological normal endometrium herald the transition from high- to low-risk endometrium."

The study involved 72 women undergoing either gastric bypass or sleeve gastrectomy, with a median BMI of 52.1 and an excess body weight of 76.6 kg at baseline. Almost two-thirds of the group (64%) were either insulin resistant or had type 2 diabetes.

Blood and endometrial tissue samples were obtained immediately before surgery, and again at 2 and 12 months follow-up. Endometrial samples were quantified for oncogenic signaling pathways and hormone receptor status, while circulating biomarkers of insulin resistance, reproductive function, and inflammation were also measured at the same time points.

"Of the six women with AH, resolution occurred in three women within 2 months of bariatric surgery following weight loss of 9-22% of their total body weight and in two other women within 6 months with intrauterine progestin," the researchers reported.

At up to 4 years of follow-up, AH had not recurred in five of the women whose endometrium was managed non-surgically, the team added.

Furthermore, significant reductions in endometrial signaling pathways including Ki-67 and glandular phosphorylated AKT (pAKT) expression were also observed at both follow-up time points. At both 2 and 12 months, median Ki-67 scores were approximately 15% lower (P=0.009 and P=0.034, respectively), while median pAKT expression levels were also about 15% lower at 2 months (P=0.03) and 12% lower at 12 months (P=0.002) following surgery.

At baseline, biopsies were glandular PTEN null in 12 of 72 women, including in seven of 10 women with baseline endometrial abnormalities. At follow-up, six of the seven women regained glandular PTEN expression that coincided with resolution of their endometrial abnormalities.

Crosbie's group reported significant reductions in markers of insulin resistance, reproductive function, and inflammation once women had lost significant amounts of weight. The striking sustained resolution of AH in most women provides "compelling" evidence that obesity promotes the development of endometrial neoplasia, they pointed out.

"In the context of the current global obesity crisis and consequent emerging epidemic of EC, this may have important implications for the screening, prevention, and treatment of EC," they suggested.

Study limitations included the small sample size and lack of a weight-stable, BMI-matched control group.

Pamela Goodwin, MD, of the University of Toronto, told MedPage Today that the study was interesting and important, and suggested that weight loss as a result of bariatric surgery may reduce endometrial cancer risk in obese women.

"After bariatric surgery, significant decreases were seen in metabolic and tissue factors that have been associated with cancer, notably reductions in insulin resistance and inflammation as well as proliferation and markers of proliferative signaling within endometrial tissue," she wrote in an email. "These findings are consistent with prior reports that endometrial cancer risk is reduced after bariatric surgery."

However, she cautioned that the fact that endometrial cancer regressed in three of six women without additional intervention was important, and required replication in a larger dataset that includes a control group who did not undergo bariatric surgery.

Nevertheless, "the results of this study provide support for intervention research involving weight loss as a potential means of lowering endometrial cancer risk and reversing endometrial hyperplasia in obese women," [while] the tissue markers may also serve to identify women at increased future risk of developing endometrial cancer," Goodwin stated.

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