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. 2013 Dec 5;5(1):76.
doi: 10.1186/1758-5996-5-76.

Does Metformin affect ER, PR, IGF-1R, β-catenin and PAX-2 expression in women with diabetes mellitus and endometrial cancer?

Anna Markowska, Monika Pawałowska  1 , Violetta Filas, Konstanty Korski, Marian Gryboś, Stefan Sajdak, Anita Olejek, Wiesława Bednarek, Beata Spiewankiewicz, Jolanta Lubin, Janina Markowska
Affiliations

Does Metformin affect ER, PR, IGF-1R, β-catenin and PAX-2 expression in women with diabetes mellitus and endometrial cancer?

Anna Markowska et al. Diabetol Metab Syndr. .

Abstract

Objective: Diabetes mellitus, as a risk factor for endometrial cancer (EC), causes an increase in insulin and IGF-1 concentrations in the blood serum. The increase in insulin and IGF-1 are considered mitogenic factors contributory to cancer development. Studies suggest that metformin has preventive activity, decreasing mortality and the risk of neoplasms. Since estrogen (ER), progesterone (PR) and IGF-1 (IGF-1R) receptor expression and β-catenin and PAX-2 mutations are significant in the development of endometrial cancer, it was decided to study these factors in patients with endometrial cancer and type 2 diabetes mellitus (DM2), and to establish the effects of metformin on their expression.

Methods: The expression of ER, PR, IGF-1R, β-catenin and PAX-2 have been immunohistochemically investigated in 86 type I endometrial cancer specimens. Patients were grouped according to the presence of DM2 and the type of hypoglycemic treatment administered.

Results: Comparing EC patients with DM2 and normal glycemic status, we found increased IGF-1R expression in women with DM2. A decrease in ER expression was noted in women with EC and DM2 receiving metformin as compared to women treated with insulin (p = 0.004). There was no statistically significant difference in PR, IGF-1R, β-catenin and PAX-2 expression among women receiving metformin and other hypoglycemic treatment.

Conclusion: Although epidemiological studies suggest the beneficial role of metformin in many human cancers, there are still few studies confirming its favorable effect on endometrial cancer. Decreased ER expression in patients receiving metformin needs further research to allow evaluation of its clinical significance.

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Figures

Figure 1
Figure 1
Different intensities of nuclear immunostaining for ER. A- no; B- weak; C- intermediate, D- strong intensity of staining.
Figure 2
Figure 2
Different intensities of nuclear immunostaining for PR. A- no; B- weak; C- intermediate, D- strong intensity of staining.
Figure 3
Figure 3
Nuclear immunostaining for nuclear PAX-2 (A) and IGF-1R membranous type of staining (B).
Figure 4
Figure 4
Membranous (A) and nuclear (B) type of immunostaining for β-catenin.
Figure 5
Figure 5
ER expression (score) in endometrial cancer cells according to presence of diabetes and method of its treatment. M- metformin, I- insulin, SD- sulfonylurea derivatives.
See this image and copyright information in PMC

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