Evaluation of the one-step nucleic acid amplification method for rapid detection of lymph node metastases in endometrial cancer: prospective, multicenter, comparative study.

OBJECTIVE: To evaluate the diagnostic performance of the one-step nucleic acid amplification (OSNA) method for the detection of sentinel lymph node (SLN) metastases in women with apparent early-stage endometrial cancer compared with standard ultrastaging. METHODS: Prospective, multicentric, interventional study. Patients with apparent early-stage endometrial cancer who underwent primary surgical staging with SLN mapping were included. SLNs were serially sectioned with 2 mm slices perpendicular to the longest axis of the node: the odd slices were submitted to ultrastaging, whereas the even slices were submitted to the OSNA analysis. Diagnostic performance was calculated taking ultrastaging as referral standard. RESULTS: Three-hundred and sixteen patients with 668 SLNs were included. OSNA assay detected 22 (3.3%) positive SLNs, of which 17 (2.5%) were micrometastases and 5 (0.7%) macrometastases, whereas ultrastaging detected 24 (3.6%) positive SLNs, of which 15 (2.2%) were micrometastases and 9 (1.3%) macrometastases (p=0.48). Regarding negative SLNs, OSNA detected 646 (96.7%) negative nodes, including 8 (1.2%) isolated tumor cells, while ultrastaging detected 644 (96.4%) negative nodes with 26 (3.9%) isolated tumor cells. Specificity of OSNA was 98.4% (95% CI 97.5 to 99.4), accuracy was 96.7% (95% CI 95.4 to 98.1), sensitivity was 50% (95% CI 30.0 to 70.0), while negative predictive value was 98.1% (95% CI 97.1 to 99.2). Discordant results were found in 22 SLNs (3.3%) corresponding to 20 patients (6.3%). These were 10 (1.5%) false-positive SLNs (all micrometastases): one (0.1%) of these was a benign epithelial inclusion at ultrastaging. There were 12 (1.8%) false-negative SLNs of OSNA, of which 9 (1.3%) were micrometastases and 3 (0.5%) macrometastases. Overall, 17/668 (2.5%) benign epithelial inclusions were detected at ultrastaging. CONCLUSION: The OSNA method had high specificity and high accuracy in detecting SLN metastasis in apparent early-stage endometrial cancer. The advantage of the OSNA method could be represented as the possibility to analyze the entire lymph node thus eliminating sampling bias.

Back to the future: The impact of oestrogen receptor profile in the era of molecular endometrial cancer classification.

PURPOSE: The aim of this study is to evaluate the impact of the oestrogen receptor (ER) profile on oncologic outcomes in the new endometrial cancer (EC) risk classification. METHODS: Immunohistochemistry (IHC) analyses were performed in a retrospectively reviewed large series of ECs to assess the presence/absence of oestrogen receptors (ER0\1+ or ER2+\3+) and other molecular factors (i.e. p53 mutation, p53mut; and mismatch repair mutational status, MMRd (mismatch repair deficient) versus MMRp (mismatch repair proficient)), histopathologic and clinical outcomes. ER status was correlated with molecular, histologic, clinical and prognostic data. RESULTS: 891 EC patients were included in the study (211 ER0\1+ and 680 ER2+\3+). The ER0\1+ phenotype was associated with an unfavourable clinicopathological profile (i.e. grading, histotype, lymphovascular space invasion (LVSI), stages, etc.). Simple regression showed that risk class, p53mut, and ER0/1+ impacted on both disease-free survival (DFS) and overall survival (OS) (p < 0.05). In the ER0/1+ population, p53mut no longer influenced DFS and OS (p > 0.05). In multiple regression, age, high and advanced/metastatic risk classes influenced survival outcomes (p < 0.05), but lost significance in the ER0/1+ population (p > 0.05). ER-positivity retained a remarkable prognostic impact even after stratification of the population according to the European Society of Gynaecological Oncology, the European Society for Radiotherapy and Oncology, and the European Society of Pathology (ESGO/ESTRO/ESP) 2021 risk classes and molecular classification. ER0/1+ intermediate, high-intermediate, high and advanced risk versus ER2+/3+ intermediate, high-intermediate, high and advanced risk classes showed statistically different OS and DFS (p< 0.001). ER0/1+ status was associated with a worse prognosis when associated with MMRp, MMRd and p53mut compared to the same molecular classes associated with ER2+/3 (p < 0.001). CONCLUSIONS: We demonstrated that ER status has a significant impact on oncologic outcomes, regardless of risk class and p53/MMR status. Based on our results, we recommend the inclusion of ER assessment in featured EC risk classification system.