Prognostic Marker In Endometrial Cancer Research Articles

2-DE protein expression in endometrial carcinoma

The objective of this study was to explore the protein expression pattern in normal endometrial mucosa (n = 5) and endometrial carcinoma (n = 15) of low (diploid) and high (aneuploid) malignancy potential by two-dimensional gel electrophoresis (2-DE). The specimens were evaluated for histopathologic subtype, stage and grade in relation to DNA ploidy. A match-set consisting of five samples from normal endometrium, eight diploid and seven aneuploid tumours was created. All the diploid and three of the aneuploid tumours were of endometrioid subtype, while the remaining four were of uterine seropapillary type. There were 192 protein spots differentiating diploid tumours from normal endometrium and 238 protein spots were separating aneuploid tumours from normal endometrium (p < 0.01). A cluster analysis based on 52 significantly deviating protein spots within the groups showed clustering and separation of the normal endometrium, diploid and aneuploid tumours. In conclusion this study showed significant differences in protein expression between normal endometrium and endometrial carcinoma as well as between endometrial carcinoma of low and high malignancy potential. In future studies these results may provide useful in finding new sensitive prognostic markers for endometrial cancer.

EZH2 Expression Is Associated With High Proliferation Rate and Aggressive Tumor Subgroups in Cutaneous Melanoma and Cancers of the Endometrium, Prostate, and Breast

EZH2 is a member of the polycomb group of genes and important in cell cycle regulation. Increased expression of EZH2 has been associated previously with invasive growth and aggressive clinical behavior in prostate and breast cancer, but the relationship with tumor cell proliferation has not been examined in human tumors. The purpose of this study was to validate previous findings in a population-based setting, also including tumors that have not been studied previously. In our study of nearly 700 patients, we examined EZH2 expression and its association with tumor cell proliferation and other tumor markers, clinical features, and prognosis in cutaneous melanoma and cancers of the endometrium, prostate, and breast. Strong EZH2 expression was associated with increased tumor cell proliferation in all four cancer types. Associations were also found between EZH2 and important clinicopathologic variables. EZH2 expression showed significant prognostic impact in melanoma, prostate, and endometrial carcinoma in univariate survival analyses, and revealed independent prognostic importance in carcinoma of the endometrium and prostate. CONCLUSION Our findings point at EZH2 as a novel and independent prognostic marker in endometrial cancer, and validate previous findings on prostate and breast cancer. Further, EZH2 expression was associated with features of aggressive cutaneous melanoma. The fact that EZH2 might identify increased tumor cell proliferation and aggressive subgroups in several cancers may be of practical interest because the polycomb group proteins have been suggested as candidates for targeted therapy. EZH2 expression should, therefore, be further examined as a possible predictive factor.

Lysosomal protease cathepsin D is a prognostic marker in endometrial cancer

The present study investigates the prognostic value of immunohistochemically detected cathepsin D expression in endometrial adenocarcinoma. Patients with surgically treated endometrial adenocarcinoma FIGO stages I-III and consecutive irradiation therapy were included in the study. When we performed immunohistochemistry to detect cathepsin D in 115 tissue specimens 35 cases showed a positive reaction. In the univariate analysis cathepsin D expression showed significant prognostic value for overall survival (P-value = 0.007). In the multivariate analysis with established prognostic parameters (stage, grade) we found an independent prognostic value for cathepsin D (P-value = 0.002, relative risk = 3.8, 95% confidence interval 1.4 - 10.0). Immunohistochemical detection of cathepsin D could aid in predicting prognosis and planning therapy for patients with endometrial adenocarcinoma.

The plasminogen activator urokinase and its inhibitor PAI-2 in endometrial cancer

Invasion and metastasis of malignant cells require the disruption of the extracellular matrix, degradation of basement membranes, and intrusion into connective tissue and vascular and lymphatic spaces. Several studies have indicated a role for urokinase (u-PA) in proteolysis of the extracellular matrix and hence in stromal invasion and metastasis. Many malignant cells are known to secrete u-PA. Plasminogen activator inhibitor-type 2 (PAI-2) is an inhibitor of u-PA and is present in several neoplastic cell lines and malignant ascites. We measured u-PA and PAI-2 antigen in tissue homogenates of normal and malignant endometrium from 21 postmenopausal patients. Enzyme-linked immunoassays which measure the bound and unbound, single-and two-chain form of the activator and bound and unbound form of the inhibitor were used. Urokinase was present in four of seven normal (range, 0.15–0.5; median, 0.15 ng/mg protein) and in significantly higher concentrations in all malignant endometrial homogenates (range, 0.41–9.2; median, 3.4 ng/mg protein), P < 0.001. PAI-2 was detectable in four of seven normal endometrial homogenates at low concentrations (range, 1.1–3.1; median, 1.1 ng/mg protein) and in all malignant tissue homogenates at significantly higher levels (range, 1.6–27.3; median, 4.9 ng/mg protein), P < 0.01. Levels of endometrial PAI-2 were higher in stages IC or greater compared to those in stages IA and 1B cancers ( P < 0.05). PAI-2 may be useful as a prognostic marker in endometrial cancer.