One-step nucleic acid amplification assay for intraoperative prediction of advanced axillary lymph node metastases in breast cancer patients with sentinel lymph node metastasis

Abstract

The one-step nucleic acid amplification (OSNA) assay is used to semiquantitatively measure the cytokeratin (CK)19 mRNA copy numbers of each sentinel lymph node (SLN) in breast cancer patients. The aim of the present study was to evaluate whether the diagnosis of ≥4 LN metastases is possible using the OSNA assay intraoperatively. Between May, 2010 and December, 2014, a total of 134 patients who underwent axillary lymph node dissection (ALND) of positive SLNs were analyzed. The total tumor load (TTL) was defined as the total CK19 mRNA copies of all positive SLNs. The correlation between TTL and ≥4 LN metastases was evaluated. Of the 134 patients, 31 (23.1%) had ≥4 LN metastases. TTL ≥5.4×10 copies/µl evaluated by receiver operator characteristic curve analysis was examined along with other clinicopathological variables. In the multivariate analysis, only TTL ≥5.4×10 copies/µl was correlated with ≥4 LN metastases (odds ratio = 2.95, 95% confidence interval: 1.17-7.97, P=0.022). Therefore, TTL assessed by the OSNA assay has the potential to be a predictor of ≥4 LN metastases and it may be useful for the selection of patients with positive SLNs in whom ALND may be safely omitted.

Intraoperative prediction of the two axillary lymph node macrometastases threshold in patients with breast cancer using a one-step nucleic acid cytokeratin-19 amplification assay

“…However, the majority of these prediction models were constructed using predictors derived from breast resection specimen pathology, such as lymphovascular invasion, and have not been widely adopted as they fail to confidently facilitate one-stage intraoperative decision making about the role of ALND. A small number of studies have reported on the prediction of NSLN metastases in SLN-positive patients, including the use of SLN OSNA TTL ( 7 , 18 , 19 ).…”

“…A study by Kubota et al ( 18 ) reported a single-centre standardised method for SLN detection that used indocyanine green; whereas, the types of injection and the use of radioisotope, with or without dye, varied according to institutional practice in a multi-centre study by Piñero-Madrona et al ( 19 ). The present single-centre dual technique of SLN detection is uniform and standardised ( 9 ).…”

One‐step nucleic acid amplification CK19 copy number for sentinel node biopsy in breast cancer: Identification of new cutoffs to predict nonsentinel axillary node involvement

“…Banerjee et al produced a stratified TTL cutoff of avoiding ALND if TTL < 1400 copies and proceeding with ALND if TTL > 7500 copies with the intermediate group depending on the degree of lymphovascular invasion 9 . Kubota et al 12 examined the correlation of TTL with having more than four positive lymph nodes and identified a cutoff of 54 000 copies (sensitivity 74%; specificity 59%). Shimazu et al 15 have shown TTL to be both significantly associated with higher nodal involvement as well as the presence of four or more positive nodes.…”

“…Given this, OSNA can be predictive of four node involvement with a copy number of >100 000 copies/µL 7 and total tumor load (TTL—total of copy numbers in submitted nodes) can be used to differentiate patients using Z0011 criteria 8 . TTL has proven a focus of research with multiple studies showing it to be an independent predictor of higher nodal involvement 9‐12 …”

Clinical significance of MSKCC nomogram on guiding the application of touch imprint cytology and frozen section in intraoperative assessment of breast sentinel lymph nodes

“…Over the past decade, many researchers are keen to apply molecular assays to improve intra-operative pathologic accuracy of breast SLNs, such as the Metasin assay [ 18 , 19 ] and one-step nucleic acid amplification assay (OSNA) [ 20 , 21 ], but neglect to give full consideration to the existing mature pathologic techniques (TIC and FS), which are widely used in clinical practice. In addition, a study of OSNA in 552 patients showed both OSNA and TIC can serve as qualified intra-operative assessments of SLNs, and suggested that OSNA can be applied as a complement to histopathologic assessment, but cannot replace pathology with serial sectioning [ 22 ].…”