Incidence and possible pathogenesis of sentinel node micrometastases in ductal carcinoma in situ of the breast detected using molecular whole lymph node assay

Division of Pathology, the Cancer Institute of the Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo 135-8550, Japan.
British Journal of Cancer (Impact Factor: 4.84). 04/2012; 106(10):1675-81. DOI: 10.1038/bjc.2012.168
Source: PubMed


The pathogenesis of lymph node metastases in preinvasive breast cancer – ductal carcinoma in situ (DCIS) – remains controversial. The one-step nucleic acid amplification (OSNA) assay is a novel molecular method that can assess a whole node and detect clinically relevant metastases. In this retrospective cohort study, we determined the performance of the OSNA assay in DCIS and the pathogenesis of node-positive DCIS.
The subjects consisted of 623 patients with DCIS who underwent sentinel lymph node (SN) biopsy. Of these, 2-mm-sectioned nodes were examined using frozen-section (FS) histology in 338 patients between 2007 and 2009, while 285 underwent OSNA whole node assays between 2009 and 2011. The SN-positivity rate was compared between cohorts, and the characteristics of OSNA-positive DCIS were investigated.
The OSNA detected more cases of SN metastases than FS histology (12 out of 285, 4.2% vs 1 out of 338, 0.3%). Most of the metastases were micrometastases. The characteristics of high-risk DCIS (i.e., mass formation, size, grade, and comedo) and preoperative breast biopsy (i.e., methods or time to surgery) were not valid for OSNA assay–positive DCIS.
The OSNA detects more SN metastases in DCIS than FS histology. Further examination of the primary tumours and follow-up of node-positive DCIS are needed to elucidate the pathogenesis.

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Available from: Takuji Iwase, Mar 02, 2015
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    • "In clinical practice, the OSNA assay can contribute to the accurate, reproducible, and standardised evaluation of the residual tumour burden after preoperative chemotherapy. When a whole lymph node or a large amount of a node is examined using the OSNA assay, more micrometastases can be detected than by the use of routine pathological examinations (Osako et al, 2011a, 2011b, 2012; Remoundos et al, 2013). This is reasonable considering that routine pathology analyses only limited a part of the lymph node, whereas the OSNA assay can thoroughly evaluate the entire lymph node. "
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    ABSTRACT: Background: For patients with breast cancer treated with preoperative chemotherapy, residual tumour burden in lymph nodes is the strongest prognostic factor. However, conventional pathological examination has limitations that hinder the accurate and reproducible measurement. The one-step nucleic acid amplification (OSNA) assay is a novel molecular method for detecting nodal metastasis. In this prospective multicentre trial, we assessed the performance of the OSNA assay in detecting nodal metastasis after chemotherapy. Methods: In total, 302 lymph nodes from 80 breast cancer patients who underwent axillary dissection after chemotherapy were analysed. Each node was cut into two or four slices. One piece or alternate pieces were evaluated by pathology, and the other(s) were examined using the OSNA assay. The results of the two methods were compared. Stromal fibrosis, histiocytic aggregates, and degenerated cancer cells were regarded as chemotherapy-induced histological changes. Results: The overall accuracy, sensitivity, and specificity of the OSNA assay compared with the reference pathology were 91.1%, 88.3%, and 91.7%, respectively. Of the 302 lymph nodes, 66 (21.9%) exhibited chemotherapy-induced histology. For these nodes, the accuracy, sensitivity, and specificity were 90.9%, 88.9%, and 93.3%, respectively. Conclusion: The OSNA assay can detect the residual tumour burden as accurately as conventional pathology, although chemotherapy-induced histological changes are present.
    British Journal of Cancer 09/2013; 109(6). DOI:10.1038/bjc.2013.503 · 4.84 Impact Factor
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    • "The most common explanation to this is that the pathologist's analysis was not thorough enough to detect the microinfiltration foci responsible for these events (Intra et al, 2008), although some other reasons have been suggested for the appearance of these cells in the sentinel node (Banys et al, 2012). For invasive breast cancer, some authors group these phenomena as benign mechanical transport, and two main modes have been proposed: surgeryinduced tumour cell displacement (Osako et al, 2012) and breast massage used to facilitate the intraoperative localisation of sentinel nodes (Diaz et al, 2005). "
    British Journal of Cancer 03/2013; 108(9). DOI:10.1038/bjc.2013.133 · 4.84 Impact Factor
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    ABSTRACT: Objective: The one-step nucleic acid amplification (OSNA) assay can assess an entire lymph node and detect clinically relevant metastases quantified based on cytokeratin 19 (CK19) mRNA copy number. The OSNA assay of all sentinel lymph nodes (SNs) and non-sentinel nodes (non-SNs) allows for the accurate measurement of tumour burden in either situation. We aim to reveal the usefulness of the OSNA assay regarding the prediction of non-SN metastasis. Methods: The subjects consisted of 185 breast cancer patients who underwent axillary dissection after a metastatic SN biopsy and whose SNs and non-SNs were examined using the OSNA whole-node assay between 2009 and 2011. The non-SN tumour burden was classified as macrometastasis (CK19 mRNA ≥ 5000 copies/μl) or micrometastasis (250-5000 copies/μl). The relationship between SN and non-SN tumour burdens and predictors of non-SN metastasis were investigated. Results: Among these 185 patients, 38 patients (20.5%) had macrometastasis and 58 (31.4%) had micrometastasis only in the non-SNs. Non-SN macrometastasis rates increased in direct proportion to the SN copy number: approximately 5% in patients with SNs with 250-500 copies; 20%, 500-5000 copies and 30%, ≥ 5000 copies. However, non-SN micrometastasis rates were approximately 30% regardless of the SN copy number. In multivariate analyses, the mean SN copy number, number of macrometastatic SN and lymphovascular invasion were significant for identifying non-SN macrometastases. Conclusions: The SN tumour burden quantified using the OSNA assay predicts non-SN metastases. A novel mathematical model to predict the non-SN tumour burden can be generated using the results of the OSNA assay.
    European journal of cancer (Oxford, England: 1990) 12/2012; 49(6). DOI:10.1016/j.ejca.2012.11.022 · 5.42 Impact Factor
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