Abstract P3-03-02: Molecular Detection of Micrometastasis in Sentinel Lymph Nodes Using One-Step Nucleic Acid Amplification Assay for Breast Cancer Patients — Comparison with Routine Pathological Examination
Authors: Osako T , Iwase T , Horii R , Kimura K , Yamashita K , Ito Y , Akiyama F. 
Published: April 2011

Abstract
Background:
In AJCC 7th edition, Stage I breast tumors have been subdivided into Stage IA and Stage IB; Stage IB includes small tumors (T1) with exclusively micrometastases in lymph nodes (N1mi), in order to facilitate further investigation. However, it is obvious that the current routine pathological examination has the limitation to detect micrometastasis, because it can examine only a part of lymph node.
One-Step Nucleic acid Amplification (OSNA) assay was developed to overcome this limitation of the routine pathological examination. This assay can classify the patients into 4 categories, (++), (+), (+I), and negative. (++) and (+I) are theoretically regarded as high-volume metastasis corresponding to macrometastasis, and (+) as low-volume metastasis corresponding to micrometastasis. Since OSNA has the potential for standardization and semi-quantitative assay for evaluating the amount of tumor cells in a lymph node, we decided to apply a whole node into OSNA assay to maximize the semi-quantitative advantage in clinical settings. In the present study, we report the results of sentinel node (SN) examination with whole node OSNA assay. And we compare the results with the pathological examination to reveal the characteristics of OSNA assay. Patients and Methods:
Data of 961 patients from January 2008 to March 2010 with clinically node-negative and pT1 breast cancer and having received SN biopsy with the radioactive tracer were evaluated. SNs were examined by whole node OSNA assay with Gene Amplification Detector RD-100i and Lynoamp®BC or 2mm-thick intraoperative frozen section with H&E staining for 442 and 519 patients respectively.
We compared the performance of whole node OSNA assay and the pathological examination. And we performed two-population-z-test. Results:
1) SN positive rates of whole node OSNA assay and the pathological examination in T1 patients were 88/442 (19.9%, 95% CI; 16.3-24.0%) and 77/519 (14.8%, 95% CI; 11.9-18.3%), respectively. The difference was 5.1% (95% CI; 0.1-9.6%, p=0.046).
2) The populations of OSNA (++) or (+I) and macrometastasis were 51/442 (11.5%, 95% CI; 8.8-15.0%) and 55/519 (10.6%, 95% CI; 8.1-13.6%), respectively. There was no significant difference. On the other hand, the populations of OSNA (+) and micrometastasis were 37/442 (8.4%, 95% CI; 6.0-11.5%) and 22/519 (4.2%, 95% CI; 2.7-6.4%), respectively. The difference was 4.1% (95% CI; 0.9-7.0%, p=0.012).
Conclusions:
OSNA assay could detect more low-volume metastases corresponding to micrometastasis than the routine pathological examination. Therefore, it is suggested that OSNA can select accurate SN/micrometastasis cohort. Follow up of the patients is required to clarify the prognosis of OSNA (+) patients, and as the result, it may be possible to establish the new breast cancer staging system using OSNA results.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-03-02.