Published: Apr 12, 2013
By Charles Bankhead , Staff Writer, MedPage Today

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WASHINGTON – Obese women at increased risk of endometrial cancer had significant reductions in cancer-associated biomarkers following bariatric surgery, and abnormal endometrial pathology resolved in three cases, investigators reported here.

Expression of hormone receptors and CD20-positive cells decreased significantly (P<0.005, P=0.0196, respectively). A reduction in expression of CD3-positive cells achieved borderline significance, and a strong trend toward lower levels of the proliferation marker Ki-67 was observed.

The findings raised the question of whether weight loss might reverse or prevent endometrial cancer, Faina Linkov, PhD, and colleagues concluded in a poster presentation at the American Association for Cancer Research meeting.

“Our data demonstrate that endometrial pathology appears to be partially mitigated by weight loss through bariatric surgery, which reduces the expression of cellular proliferation markers, inflammation, and hormone receptors, suggesting these pathways may be relevant in the pathogenesis of endometrial cancer,” said Linkov, of the University of Pittsburgh.

In a second presentation at AACR, Linkov and her associates reported significant associations between change in body mass index (BMI) and reductions in multiple cancer-related biomarkers among participants in two clinical trials of behavioral weight-loss interventions.

The growing obesity epidemic in the U.S. and other Western nations has increased recognition of excess body weight’s associations with cancer, possibly driven by low-grade systemic inflammation, one of the consequences of obesity.

Endometrial cancer is one of several malignancies associated with obesity. Whether weight loss influences the association has remained unclear. To examine the issue, Linkov and colleagues compared endometrial biopsies obtained from morbidly obese women before bariatric surgery and a year afterward.

Biopsy specimens obtained before surgery and a year later were evaluated by immunohistochemical staining for estrogen receptor, progesterone receptor, androgen receptor, Ki-67, and the immune-response activators CD3 and CD20.

The investigators enrolled 59 patients, about half of whom had paired biopsy specimens for evaluation. The patients had a mean age of 42, mean preoperative weight of 279 pounds, and mean BMI of 46.8. Four of the women exhibited endometrial hyperplasia without atypia prior to surgery (which was Roux-en-Y gastric bypass in all cases).

Three of the four women with endometrial hyperplasia before surgery had paired biopsies. Comparison of pre- and postop biopsy specimens showed all three women had complete resolution of abnormal pathology, within 1 year in two of the women and within 2 years in the third. The pathologic changes were associated with substantial decreases in expression of estrogen receptor and androgen receptor.

Among 14 patients who had low-level Ki-67 activity at baseline, nine continued to have low levels of the marker a year later, but the others had increased activity (P=0.0104). However, 14 women had moderate to very-high Ki-67 expression at baseline, and 10 of those patients had converted to low-level expression by the follow-up biopsy (P<0.0001). Because of the small sample size, neither value met criteria for statistical significance.

Most of the women had low or moderate baseline expression of CD3-positive cells, and the percentage did not change substantially after surgery. However, six women had high-level expression, which decreased to moderate expression in five patients and low expression in the other (P=0.0504).

The second report by Linkov and colleagues involved 68 participants (18 men) in two clinical trials of behavioral weight-loss interventions. The patients weighed an average of 210 pounds at baseline and 172 pounds a year later. BMI averaged 33 at baseline and had declined by 5 to 6 units at the 1-year follow-up.

After obtaining serum samples at baseline and 1 year, the investigators used a panel of 26 immunoassays to evaluate changes in cancer-related antigens, proinflammatory cytokines, hormones, and growth factors.

The results showed statistically significant associations between decline in BMI and reductions in adiponectin, C-reactive protein, C-peptide, insulin-like growth factor 1, insulin, plasminogen activator inhibitor 1, and soluble E-selectin.

The findings from the surgical study are particularly noteworthy because they reinforce the biologic link between obesity and malignancy but more importantly, provide evidence that weight loss by bariatric surgery might have a dramatic effect on cancer-related biomarker, said Candace Johnson, PhD, of Roswell Park Cancer Institute in Buffalo, N.Y., who was not involved in the study.

“Most people know that obesity is a high-risk factor for malignancy, for bad health in general,” Johnson told MedPage Today. “But [the idea] that you could change markers that may predispose you to a premalignant condition in endometrial cancer is very interesting.

“These women undergo surgery and then dramatically reduce their caloric intake, and this, in and of itself, can reduce these markers. There hasn’t been a lot of work done in this, and that makes these findings interesting and potentially significant.”

The study required partnering between clinicians and researchers in gynecologic oncology with bariatric surgeons, another notable aspect of the work because it emphasizes the importance of interdisciplinary collaboration in addressing problems in oncology, she added.