Carcinoma of the endometrium: prediction markers of tumour progression, aggressiveness and potential targets for therapy in a mitochondrial perspective

Mints M.

M. Mintz, MD, PhD, Associated Professor

Department of Women’s and Children’s Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Karolinska University Hospital 171 76, Stockholm, Sweden

Endometrial cancer (EC) is the most common gynaecological cancer in the Western world, and its incidence continues to increase. At present, molecular markers are not commonly used to detect EC, nor are there molecular markers that can distinguish between the more and less aggressive forms of EC. Treatment is currently based on histological results from a single pre-surgical endometrial biopsy, which is often quite different from the biopsy obtained during surgery. There is a clear need for early molecular markers that can be used to determine EC diagnosis, as well as tumour progression and aggressiveness, in order to improve the prognosis of EC and to reduce recurrence. Further investigation of tumour gene mutations is also needed to find new targeted treatments for EC.

We summarized the known molecular alterations that occur in EC, with a focus on mitochondrial alterations, and the potential to use these alterations to develop targeted treatments in the future. Studies concerning mitochondrial dysfunction in carcinogenesis reported that the LRPPRC protein is highly expressed in early endometrial carcinogenesis, and may be considered an early marker of EC. Moreover, four proteins were reported to be molecular markers of aggressiveness in patients with EC: 1) the ratio of progesterone receptor (PR) A/PR B less than 1 was associated with a shorter disease-free period and shorter survival in patients with endometrioid EC; 2) glucose transporter proteins (GLUT 1 and GLUT 3) were correlated with increased malignancy, invasiveness and poor prognosis; and 3) the TKTL1 protein was overexpressed in low-grade EC.

Currently, there are no tumour markers that can resolve diagnostic problems in EC. The present review indicates that molecular markers and tumour characteristics greatly vary. Consequently, a combination of molecular markers would be necessary to give information on early diagnosis, tumour progression and metastatic capability.

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