# Diagnostic value of one-step nucleic acid amplification for sentinel lymph node metastasis in cytokeratin 19-positive tumors: evidence from bioinformatics and meta-analysis

## TL;DR

This study evaluates the OSNA test for detecting cancer spread in sentinel lymph nodes, showing it is accurate in several cancers but needs more research in others.

## Contribution

The study provides a comprehensive meta-analysis of OSNA's diagnostic accuracy across multiple CK19-positive cancers.

## Key findings

- OSNA showed a pooled sensitivity of 0.87 and specificity of 0.95 for detecting sentinel lymph node metastasis.
- OSNA was found to be stable in breast cancer across different populations and medical centers.
- Using a 250 copies/μl cutoff for CK19 mRNA improved sensitivity and AUC for micro-metastasis detection.

## Abstract

The status of the sentinel lymph nodes (SLNs) was an important prognostic factor in varies cancers. A one-step nucleic acid amplification (OSNA) assay, a molecular-based whole-node analysis method based on CK19 mRNA copy number, was developed to diagnose lymph node metastases. We aimed to evaluate the value of OSNA for the diagnosis of sentinel lymph node metastasis in CK19 positive cancers. CK19 mRNA and protein expression for pan-caner analysis were obtained from TCGA and the Human protein atlas database.

Two researchers independently searched the PubMed, Cochrane Library and Web of Science databases for qualified articles published before December 1, 2023. A meta-analysis was performed using MetaDisc and STATA. Risk bias and quality assessments of the included studies were evaluated, and a subgroup analysis was performed. Ten cancer types were found to be CK19 positively expressed and 7 of 10 had been reported to use OSNA for SLN detection.

After literature review, there were 61 articles included in the meta-analysis, which consisted of 7115 patients with 18007 sentinel lymph nodes. The pooled sensitivity and specificity of OSNA were 0.87 and 0.95 in overall patients. Moreover, we found the background CK19 expression in normal tissue affected the diagnostic accuracy of OSNA. In breast cancer, we performed subgroup analysis. OSNA exhibited to be a stable method across different population groups and various medical centers. In addition, when 250 copies/μl was chosen as the cutoff point of CK19 mRNA, there were a relatively higher sensitivity and AUC in detecting SLN micro-metastasis than 5000 copies/μl.

OSNA can predict the occurrence of SLN metastasis accurately in CK19 positive cancers, especially in breast cancer, colorectal cancer, lung cancer, gastric cancer and endometrial cancer. Our study warrants future studies investigating the clinical application of OSNA in pancreatic, ovarian and bladder cancers.