Abstract
Background Pathologic lymph node staging is becoming a deficient method in the demanding molecular era. Nevertheless, the use of more sensitive molecular analysis for nodal staging is hampered by its high costs and extensive time requirements. Our aim is to take a step forward in colon cancer (CC) lymph node (LN) pathology diagnosis by proposing a feasible and efficient molecular method in routine practice using reverse transcription loop-mediated isothermal amplification (RT-LAMP).ResultsMolecular detection of tumor cytokeratin 19 (CK19) mRNA with RT-LAMP was performed in 3206 LNs from 188 CC patients using two methods: individual analysis of 1449 LNs from 102 patients (individual cohort), and pooled LN analysis of 1757 LNs from 86 patients (pooling cohort). A median of 13 LNs (IQR 10–18) per patient were harvested in the individual cohort, and 18 LNs (IQR 13–25) per patient in the pooling cohort (p ≤ 0.001). The median of molecular assays performed in the pooling cohort was 2 per patient (IQR 1–3), saving a median of 16 assays/patient. The number of molecular assays performed in the individual cohort was 13 (IQR 10–18), corresponding to the number of LNs to be analyzed. The sensitivity and specificity of the pooling method for LN involvement (assessed by hematoxylin and eosin) were 88.9% (95% CI 56.5–98.0) and 79.2% (95% CI 68.9–86.8), respectively; concordance, 80.2%; PPV, 33.3%; NPV, 98.4%. The individual method had 100% sensitivity (95% CI 72.2–100), 44.6% specificity (95% CI 34.8–54.7), 50% concordance, 16.4% PPV, and 100% NPV. The amount of tumor burden detected in all LNs of a case, or total tumor load (TTL) was similar in both cohorts (p = 0.228).ConclusionsLN pooling makes it possible to analyze a high number of LNs from surgical colectomies with few molecular tests per patient. This approach enables a feasible means to integrate LN molecular analysis from CC specimens into pathology diagnosis and provides a more accurate LN pathological staging with potential prognostic implications.
Highlights
Pathologic lymph node staging is becoming a deficient method in the demanding molecular era
We aimed to demonstrate the efficiency of the new procedure in the analysis of colon cancer (CC) lymph node (LN) in terms of time spent in the molecular analysis, as well as the feasibility of introducing this approach into pathology daily practice
Patients and lymph node characteristics A total of 3206 LNs from 188 colectomy specimens of surgically treated CC patients were analyzed by One Step Nucleic Acid Amplification (OSNA); 1757 LNs from 86 patients were analyzed using the pooling approach, and 1449 LNs from 102 patients were analyzed using individual LN analysis
Summary
Pathologic lymph node staging is becoming a deficient method in the demanding molecular era. The use of more sensitive molecular analysis for nodal staging is hampered by its high costs and extensive time requirements. Recently implemented CRC screening programs result in earlier stage tumor detection [22, 23]. In this setting, a more accurate diagnosis and staging is mandatory. Given the high prevalence of CRC and the high number of LNs to be analyzed, systematic molecular LN analysis or additional diagnostic methods beyond routine H&E are far from being incorporated into pathological diagnosis, mostly because of the high cost of molecular techniques and the supplementary workload
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