The real-time intra-operative evaluation of sentinel lymph nodes in breast cancer patients using One Step Nucleic Acid Amplification (OSNA) and implications for clinical decision-making
Introduction
The One Step Nucleic Acid Amplification (OSNA) method for the perioperative analysis of sentinel lymph nodes in breast cancer has recently been introduced in approximately 12 UK centres. Current NICE guidelines (2009) suggest that pre-treatment ultrasound evaluation of the axilla should be performed for all patients being investigated for early invasive breast cancer and, if morphologically abnormal lymph nodes are identified, ultrasound-guided needle sampling or core biopsy should be performed.2 In patients who have a normal axillary ultrasound or negative fine needle aspiration of a node, it is appropriate to offer sentinel lymph node (SLN) biopsy. It is current practice that a positive result on SLN biopsy should be treated with axillary dissection.3 Furthermore, recent NICE guidelines recommend OSNA for the diagnosis of sentinel node biopsy.1 Recently, several studies have proposed the intra-operative molecular-based detection of SLN metastasis using standardised quantitative calibration methods in breast cancer.5 This obviates a second operation to treat the axilla, thereby expediting progression to adjuvant treatment.4 The One Step Nucleic Acid Amplification (OSNA, Sysmex, Kobe, Japan) assay evaluates the number of mRNA copies of CK19,5 a duct epithelial cell marker, which is highly expressed in the majority (>95%) of breast cancers. The histopathology protocols to determine the sensitivity and specificity of OSNA have been described (Tsujimoto 2008, Visser 2009, Snook 2010). In this two phase study, we aimed firstly to delineate the concordance of OSNA with routine histopathological diagnosis and secondly to determine how many patients could be saved a second operation, whilst also analysing the impact on theatre operating time.
Section snippets
Patient samples
All breast cancer patients underwent axillary ultrasound ± FNA and only USS or cytologically negative patients underwent SNB. Phase 1 consisted of all patients undergoing SNB from Feb 2010 to Sept 2010 and was the validation phase of the study. During this period, axillary dissections were performed as the unit was completing its training phase in the NEWSTART sentinel node study, a national scheme for verifying competence in the sentinel node procedure. The prospective adoption of SLN analysis
Results
The study comprised 212 patients with normal lymph node morphology on axillary ultrasound (US), or US-guided cytologically normal lymph nodes. Four hundred and forty sentinel lymph nodes (SLNs) were analysed. Following SLN biopsy (SLNB) and OSNA, 62 (29%) patients underwent completion therapeutic axillary dissection, compared to the majority of patients (n = 150; 70.8%) requiring SLNB alone.
Discussion
This prospective cohort study from a single UK centre assesses the pilot data on the overall concordance rate between intra-operative OSNA and post-operative histology as 93–94%. These findings are based on standard methods of subdividing the SLN into four slices for synchronous molecular and histological diagnoses. The reported results confirm similar excellent rates of specificity and sensitivity from other studies,5, 9, 10, 11, 12, 13 as shown in Table 5. It is well described that routine
Conclusion
OSNA processing of SLNs intra-operatively is becoming more widespread in the UK. Pre-operative US diagnosis of SLN positivity is improving but is currently associated with relatively high diagnostic false-negative rates of up to 50%. This may improve with improved methods of imaging and greater use of fine needle cytology of all suspicious and equivocal nodes. We have shown that the analysis of SLN can be undertaken in routine practice with a very high accuracy and only a modest impact on
Conflict of interest
There is no conflict of interest.
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Cited by (36)
Sentinel lymph node study in breast cancer using the OSNA (one-step nucleic acid amplification) method after neoadjuvant treatment at Hospital Universitario de Navarra
2023, Revista de Senologia y Patologia MamariaSeptin 9 methylation analysis of lymph node micrometastases for predicting relapse of colorectal cancer
2022, Annals of Diagnostic PathologyCitation Excerpt :The data resulted in an upstaging of 25.2 % of patients with initially histologically negative lymph nodes from UICC-I/II to UICC-III. The same or similar strategy has also been used to detect cancer cells in resected lymph nodes of breast cancer and lung cancer patients for clinical decision-making [7,8]. In addition, immunohistochemistry (IHC) staining of lymph nodes has been described to improve the clinical staging of non-small cell lung cancer and predict prognosis and outcome [9].
The evolving role of one-step nucleic acid amplification (OSNA) for the intra-operative detection of lymph node metastases: A diagnostic accuracy meta-analysis
2021, European Journal of Surgical OncologyCitation Excerpt :CK19 is a typical epithelial cell marker expressed in human malignant cells, whilst its expression rate correlates with the size of the metastatic foci [9]. OSNA is an established technique for accurately identifying LN metastases in breast cancer (BC) [10,11]. In light of the high diagnostic performance in BC, its accuracy for detecting LN metastases has also been investigated in the context of other tumour types, including colorectal (ColCa), gastric (GasCa), gynaecological (GynCa), lung (LungCa), head and neck (HNSCC) and thyroid cancer (ThyCa), respectively.
Total tumor load assessed by one-step nucleic acid amplification assay as an intraoperative predictor for non-sentinel lymph node metastasis in breast cancer
2017, BreastCitation Excerpt :Intraoperative diagnosis of positive SLN can allow ALND in the same surgical procedure when criteria are present, thus avoiding a second surgery to treat the axilla and decreasing the patient's associated discomfort and institutional costs [2,3]. The one-step nucleic acid amplification (OSNA, Sysmex, Kobe, Japan) assay is a molecular method that measures the quantity of cytokeratin (CK)-19 mRNA (a duct epithelial cell marker that is highly expressed in more than 95% of breast cancers) in axillary lymph nodes [4]. Cutoff values were defined to classify macrometastases (more than 5000 copies/μL), micrometastases (250–5000 copies/μL) and negative nodes (fewer than 250 copies/μL) [5].