Biologic markers in endometrial cancer treatment

Abstract

With a lifetime risk among women of 2-3%, endometrial cancer is the most common pelvic gynecologic malignancy in industrialized countries. Approximately 75% of cases are diagnosed at an early stage with a tumor confined to the uterine corpus. Although most patients are cured by surgery alone, about 15-20% with no signs of locally advanced or metastatic disease at primary treatment recurs, with limited responsiveness to systemic therapy. The most common basis for determining the risk of recurrent disease has been classification of endometrial cancers into two subtypes. Type I, associated with a good prognosis, accounts for the majority of cases and is associated with a low-stage, low-grade and endometrioid histology. In contrast, type II, associated with a poor prognosis, is characterized by a high-stage, high-grade and non-endometrioid histology. However, the prognostic value of this distinction is limited, as up to 20% of type I endometrial cancers recur, while half of type II cancers do not. We review the current literature on epidemiology, etiology, pathology, molecular alterations, staging, treatment and prognostic factors in endometrial cancer. Ongoing molecular-based clinical trials and newly reported molecular alterations with a potential for development of new targeted therapy are discussed.

Biomarkers in endometrial cancer: Possible clinical applications (Review)

“…By contrast, type 2 endometrial cancer is more frequent in older women following menopause, is moderately-to poorly-differentiated and has a poor prognosis. Engelsen et al examined the rates of mutation in each biomarker for endometrial cancer of the respective types (Table I) (3). The estrogen receptor (ER), progesterone receptor (PR), K-ras and PTEN are mutated at high rates in type 1 cases, whereas the levels of p53 and HER2/neu mutation are high in type 2 cases, similar to the developmental mechanisms of the two types of endometrial cancer.…”

Biomarkers as prognostic factors in endometrial cancer.

“…Endometrial cancers are known to be heterogeneous with respect to the expression of biochemical markers, ploidy, degree of differentiation, immunogenicity [4]. The disease is rare before the age of 40, and <20% occur before menopause [5].…”

“…Overweight is present in 50% with endometrial carcinoma, and the risk is linked to disturbances in hormone metabolism related to obesity. Nulliparity is a risk factor for endometrial cancer, and breast cancer patients treated with tamoxifen have a six-to eight-fold increased risk [4,7].…”

“…This pathway is frequently activated in endometrial carcinoma through various genetic alterations and their combinations. Activation of PI3K produces the second messenger PIP3 which subsequently activates various down-stream pathways such as AKT [4,16]. Mutations in PIK3CA occur in 24-36% endometrial cancers and are coexisting with PTEN mutations in 14-26% [18].…”

“…MSI has later been found in 20-30% of endometrial carcinomas, due to epigenetic inactivation through hypermethylation of the MLHl promoter in most cases. MSI has been reported to be more common in type I than type II cancers [4,25].…”