HER2 expression patterns in paired primary and metastatic endometrial cancer lesions.

BACKGROUND: Despite successful implementation of drugs targeting the human epidermal growth factor receptor 2 (HER2) receptor in breast and gastric cancers, the potential of HER2 as a therapeutic target in other cancers has been less studied, including endometrial cancer. We investigated expression levels of HER2 (ERBB2) in a large cohort of endometrial cancer lesions, also including complex atypical hyperplasia and metastatic lesions. METHODS: 67 precursor lesions, 790 primary endometrial cancers and 383 metastatic lesions were investigated for HER2 expression in relation to clinicopathologic features and outcome. Protein levels were assessed by immunohistochemistry (using the HercepTest and staining index (SI) criteria), mRNA levels by microarrays and amplification status by chromogenic in situ hybridisation. RESULTS: High HER2 protein levels were significantly associated with features of aggressive disease and increased mRNA ERBB2 levels. HER2 expression defined by the SI proved to be a better predictor of survival compared with the HercepTest. A discordant HER2 expression pattern between paired primary and metastatic lesions was detected, revealing substantial reduction in HER2 expression from primary to metastatic disease. CONCLUSIONS: Loss of HER2 expression is common in metastatic endometrial cancer lesions and assessment of HER2 levels in the metastatic lesions may be important to define the potential benefit of anti-HER2 treatments in endometrial cancer patients.

Plasma growth differentiation factor-15 is an independent marker for aggressive disease in endometrial cancer.

OBJECTIVE: Better biomarkers are needed in order to identify patients with endometrial carcinoma at risk of recurrence and who may profit from a more aggressive treatment regimen. Our objective was to explore the applicability of plasma growth differentiation factor 15 (GDF-15) as a marker for recurrent disease, as well as a marker for poor prognosis and lymph node metastases. METHODS: EDTA-blood samples were obtained from 235 patients with endometrial cancer before primary surgery. For 36 of these patients, matching blood samples were collected at time of recurrence. Blood samples were also collected from 78 patients with endometrial hyperplasia. Plasma GDF-15 was measured by an enzyme-linked immunosorbent assay (ELISA). Preoperative pelvic MRI scans for 141 patients were investigated in parallel for imaging variables. RESULTS: Preoperative plasma level of GDF-15 was significantly higher for patients who experienced recurrence (1780 ng/L; 95% CI; 518-9475 ng/L) than for patients who did not develop recurrent disease (1236 ng/L; 95% CI; 307-7030 ng/L) (p<0.001). Plasma levels of GDF-15 at recurrence (2818 ng/L, 95% CI 2088-3548 ng/L) were significantly higher than plasma levels of GDF-15 measured at time of primary diagnosis (1857 ng/L, 95% CI; 1317-2398 ng/L) (p = 0.001). High plasma level GDF-15 independently predicts recurrent disease (OR = 3.14; 95% CI 2.10-4.76) and lymph node metastases (OR = 2.64; 95% CI 1.52-4.61). Patients with high plasma level of GDF-15 had significantly larger tumor volume (p = 0.008). CONCLUSION: Elevated plasma level of GDF-15 is associated with aggressive disease and lymph node metastasis in endometrial carcinoma. GDF-15 may be helpful in indicating recurrent disease.