The role of biomarkers in endometrial cancer and hyperplasia: a literature review

The aim of T-cell-based immune therapy for cancer has been to generate durable clinical benefit for patients. Following a generation of therapies that largely showed minimal activity, substantial toxicity, and no biomarkers to identify which patients benefit from treatment, early studies are showing signs that programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) inhibitors are highly active. Preclinical and early data from clinical studies suggest that targeting this pathway can induce durable clinical responses in patients in a variety of tumor types, including lung and colon cancer. Furthermore, correlations with tumor PD-L1 expression may enable selection of patients most likely to benefit from treatment. The emerging data not only offer the hope of better cancer therapy but also provide evidence that changes our understanding of how the host immune system interacts with human cancer. ©2012 AACR.

The dosage of soluble programmed cell death ligand 1 (sPD-L1) protein in the blood of adults with cancer has never been performed in a prospective patient cohort. We evaluated the clinical impact of sPD-L1 level measured at the time of diagnosis for newly diagnosed diffuse large B-cell lymphoma (DLBCL). Soluble PD-L1 was measured in the plasma of 288 patients enrolled in a multicenter, randomized phase III trial that compared R-high-dose chemotherapy with R-CHOP. The median follow-up was 41.4 months. A cutoff of 1.52 ng/ml of PD-L1 level was determined and related to overall survival (OS). Patients with elevated sPD-L1 experienced a poorer prognosis with a 3-year OS of 76% versus 89% (P<0.001). Considering clinical characteristics, the multivariate analysis retained this biomarker besides bone marrow involvement and abnormal lymphocyte-monocyte score as independently related to poor outcome. sPD-L1 was detectable in the plasma and not in the serum, found elevated in patients at diagnosis compared with healthy subjects and its level dropped back to normal value after CR. The intention-to-treat analysis showed that elevated sPD-L1 was associated with a poorer prognosis for patients randomized within the R-CHOP arm (P<0.001). Plasma PD-L1 protein is a potent predicting biomarker in DLBCL and may indicate usefulness of alternative therapeutic strategies using PD-1 axis inhibitors.

Postmenopausal vaginal bleeding is a common clinical problem. Endovaginal ultrasound (EVUS) is a noninvasive diagnostic test that may help determine which women should undergo endometrial biopsy. To determine the accuracy of EVUS in detecting endometrial disease in postmenopausal women with vaginal bleeding according to hormone replacement use. Literature search of English-language and non-English-language articles published from 1966 through November 1996 using MEDLINE and by a manual search of bibliographies of published articles. Studies were included if they prospectively collected EVUS measurements of endometrial thickness prior to obtaining endometrial tissue for histologic evaluation in postmenopausal women with vaginal bleeding. Of 85 studies that included data on EVUS and endometrial histology, 35 were included in the meta-analysis and included 5892 women. Articles were reviewed and independently selected and abstracted by 2 reviewers. Disagreement was resolved by consensus. The overall summary mean weighted estimates of sensitivity and specificity were calculated for thresholds of endometrial thickness from 3 to 10 mm. Using a 5-mm threshold to define abnormal endometrial thickening, 96% (95% confidence interval [CI], 94%-98%) of women with cancer had an abnormal EVUS result, whereas 92% (95% CI, 90%-93%) of women with endometrial disease (cancer, polyp, or atypical hyperplasia) had an abnormal result. This did not vary by hormone replacement use. However, the number of women with normal histology who had an abnormal EVUS result did vary by hormone replacement use. In women who were not using hormone replacement therapy, 593 (8%) with normal histological findings had an abnormal EVUS result (specificity, 92%; 95% CI, 90%-94%), whereas 1544 (23%) using hormone replacement therapy had an abnormal EVUS result (specificity, 77%; 95% CI, 75%-79%). For a postmenopausal woman with vaginal bleeding with a 10% pretest probability of endometrial cancer, her probability of cancer is 1% following a normal EVUS result. Endovaginal ultrasound has a high sensitivity for detecting endometrial cancer and other endometrial disease and can reliably identify postmenopausal women with vaginal bleeding who are highly unlikely to have significant endometrial disease so that endometrial sampling may be unnecessary.