| Objective:In recent years, breast cancer incidence rate has been the first malignant tumor disease in women, as people understanding the biological characteristics of breast cancer, revolutionary changes occurred in breast surgery, from the largest local area that can be tolerated to effective treatment of the smallest changes in the local area treatment. Axillary lymph node metastasis has been the clinical stage of breast cancer, prognosis and guiding adjuvant therapy of the most important indicators. Traditional axillary lymph node dissection (ALND) can bring to the upper limb with numbness, pain, lymphedema, dysfunction and other complications in patients, seriously impact on patients quality of life. In early breast cancer patients, sentinel lymph node biopsy (SLNB) has become a routine procedure, because it provides accurate axillary stage while sparing node-negative patients the morbidity associated with ALND.The status of axillary lymph node metastasis is to determine the prognosis of breast cancer and adjuvant therapy guidance of the most important indicator. The accurate and rapid intra-operative assessment of sentinel lymph node (SLN) has the advantage of enabling axillary lymph nodes dissetion to be performed immediately, thereby avoiding the morbidity, inconvenience and cost of a second, separate operation. In 2005 the second Image-detected breast cancer: state of the art diagnosis and treatment consensus had recommended using(Frozen Section, FS) and (Touch Imprint Cytology, TIC) as intraoperative diagnosis of SLN. But they were traditional procedures for intra-operative assessments of SLN with low sensitivity to SLN micrometastases and isolated tumor cells.One-Step Nucleic Acid Amplification (OSNA) is based on homogenization of lymph node samples followed by reverse-transcription loop-mediated isothermal amplification (RT-LAMP) for the detection of node metastases larger than 0.2mm.The aim of this study is to evaluate the roles of OSNA Assay as an intra-operative diagnostic method of SLN for breast cancer patients.Methods:113 consecutive prospective patients were enrolled in this study. If SLN<100mg, SLN was not cut, only tested by pathological examination. If 100mg≤SLN≤1200mg, as the SLN minor axis as the base (perpendicular to the short axis) equal: if the short axis<4mm, SLN was cut into two blocks, half tested by OSNA assay, the other tested by pathological examination; if the short axis≥4mm, SLN was cut into four blocks, a and c odd blocks were tested by OSNA assay, b and d even blocks by pathological examination. If SLN > 1200mg, a and c odd blocks tested by OSNA assay respectively. OSNA assay results were compared with post-operative serial section HE histology. In addition, intra-operative histological assessments were performed on the even blocks of all patients by FS and all four blocks of all patients by TIC.Results:In the patients basis analysis and by post-operative serial section histology standards, the accuracy of the OSNA was 85.8%(97/113). The performance of the OSNA was sensitivity 86.5%(32/37), specificity 85.5%(65/76), PPV 74.4%(32/43), and NPV 92.9%(65/70). For FS, the accuracy, sensitivity, specificity, PPV and NPV were95.6%(108/113),86.5%(32/37),100%(76/76),100%(32/32)and93.8%(76/81), respectively, and for TIC, they were 92.0%(104/113), 91.9%(34/37), 92.1%(70/76), 85.0%(34/40) and 95.9%(70/73), respectively. The sensitivity of the assay was similar to FS (86.5%, P=1.000) and TIC (91.9%, P= 0.454). When it came to patients with macrometastases, OSNA detected 29 of 32 (90.6%), while FS 32 of 32 (100%) and TIC 31 of 32 (96.9%) (P=0.161), When it came to patients with micrometastases, OSNA and TIC respectively detected 3 of 5 (60.0%), while FS had no detected (0%). So OSNA and TIC have a better sensitivity to micrometastases than FS (P= 0.038) In the nodes basis analysis and by post-operative serial section histology standards, the accuracy of the OSNA compared to histological evaluation was 87.6% (240/274). The OSNA performance was sensitivity 75.0% (39/52), specificity 90.5% (201/222), PPV 65.0% (39/60), and NPV 93.9% (201/214). FS performance was accuracy95.6%(262/274),sensitivity76.9%(40/52),specificity100%(222/222),PPV100%(40/40), andNPV 94.9%(222/234). TIC performance was accuracy92.0%(252/274), sensitivity 86.5%(45/52), specificity 93.2%(207/222), PPV 75.0%(45/60), and NPV 96.7%(207/214). The sensitivity of the assay was similar to FS (76.9%, P= 0.819) and TIC (86.5%, P= 0.135).After adjusting the dates, in the patients basis analysis and by post-operative serial section histology standards, the accuracy and sensitivity of the OSNA was 90.3%(102/113),88.1%(37/42), For FS, the accuracy, sensitivity were 91.2%(103/113), 76.2%(32/42) and for TIC, they were 94.7%(107/113),90.5%(38/42). The OSNA sensitivity of the trend was more apparent than FS (P= 0.154). In the nodes basis analysis and by post-operative serial section histology standards, the accuracy and sensitivity of the OSNA was 92.0%(252/274) and 79.7%(51/64), For FS, the accuracy, sensitivity were 91.2%(250/274), 62.5%(40/64) and for TIC, they were 93.4%(256/274), 82.8%(53/64). The sensitivity of the OSNA was statistically significant (P= 0.032).In this study, in the nodes basis analysis, there were 13 SLN negative tested by OSNA but were macrometastases or micrometastases by post-operative serial section histology, and then tested by immunohistochemistry, there were 12 SLN CK-19 protein expression existing(including 7 low expression and 5 high expression ), only one had no CK-19 protein expression.On patients and nodes basis analysis, OSNA[++] prediction macrometastases were 81.3%, 73.7%. After a learning curve of about 10 cases, the assay could be performed in a median time of about 36 min. OSNA had good test fees / efficiency ratio, the cost between traditional methods and OSNA in the diagnosis of SLN was similar to, but FS and TIC were huge workload and required pathologists, laboratory diagnosis of physicians and technicians a lot of time, the advantage of OSNA efficiency was obvious.Conclusion:The OSNA assay is an accurate, rapid intra-operative assay and has good fees / efficiency ratio for breast sentinel lymph nodes and it can be for application in general medical practice. |
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