Background: Sentinel lymph node (SLN) mapping with multilevel sectioning and immunohistochemistry (IHC) or one-step nucleic acid amplification (OSNA) were proposed as promising techniques for better lymph node staging in patients with colon cancer. To the best of our knowledge, this is the first study assessing the prognostic significance of OSNA compared to established investigations with hematoxylin & eosin (H&E) or IHC in patients with colon cancer.
Patients and Methods: Standard oncological resection and SLN mapping was performed from 10/2008 to 12/2013 in 177 patients with stage I-III colon cancer operated at three different institutions internationally. In all patients, SLN were examined for the presence of tumor cells with conventional H&E staining, multilevel sectioning with IHC and OSNA. Kappa statistics were used to evaluate the association (agreement) between positive H&E, IHC and OSNA status. Kaplan-Meier survival and Cox regression analysis were performed to determine the prognostic significance of either technique.
Results: There was only moderate agreement between H&E, IHC and OSNA (IHC and H&E [kappa=41%], OSNA and H&E [kappa=47%] and OSNA and IHC [kappa=38%]). Mean disease free survival (DFS) was 45.9 months for patients with positive H&E status versus 65.1 months for patients with negative H&E status (p<0.001). Mean DFS for positive vs. negative IHC status was 53.5 vs. 64.1 months (p=0.006) and for positive vs. negative OSNA status 49.2 vs. 63.9 months (p<0.001). Mean overall survival (OS) for positive vs. negative H&E status was 47.4 vs. 63.7 months (p<0.001), for positive vs. negative IHC status 53.4 vs. 63.1 months ((p=0.011) and for positive vs. negative OSNA status 50.2 vs. 62.5 months (p<0.001). In multivariable analysis, positive H&E status was prognostic for DFS (hazard ratio (HR)=2.56, p=0.048) along with positive OSNA status (HR 2.11, p=0.075) and lymph vessel invasion (HR=2.825, p=0.039). The only prognostic factors for OS were positive H&E status (HR=2.695, p=0.005) and positive OSNA status (HR=2.038, p=0.044).
Conclusions: This study demonstrates that SLN examination with H&E, IHC and OSNA produces discordant findings in most patients. Although all three techniques could identify patients with decreased survival, the combination of H&E staining and OSNA seems to be best to most accurately predict patient outcome. The clinical implications of this combination (H&E and OSNA) have to be evaluated in future oncological trials.