Clinical validation of a molecular assay for intra-operative detection of metastases in breast sentinel lymph nodes

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• 作者：M.D. Martin Martinez ; I. Veys ; S. Majjaj ; L. Lespagnard ; J.C. Schobbens ; G. Rouas ; V. Filippov ; D. Noterman ; D. Hertens ; F. Feoli ; P. Bourgeois ; V. Durbecq ; D. Larsimont ; J.M. Nogaret
• 关键词：Real-time RT-PCR ; Intra-operative sentinel lymph node biopsy ; Sentinel lymph node ; Breast cancer
• 刊名：European Journal of Surgical Oncology (EJSO)
• 出版年：2009
• 出版时间：April 2009
• 年：2009
• 卷：35
• 期：4
• 页码：387-392
• 全文大小：295 K

文摘

Background

In breast cancer patients, the status of the sentinel lymph nodes (SLNs) has been shown to accurately reflect the presence of metastases in the axillary lymph nodes (ALNs). Intra-operative SLN evaluation by frozen section histology may miss positive cases, leading to a second surgery for complete ALN dissection. Permanent section histology itself has tissue sampling limitations and is partially dependent on pathologist expertise.

Methods

A prospective study (N = 78) was conducted in our institution to validate a new intra-operative molecular assay, the GeneSearch™ breast lymph node (BLN) assay. This assay quantifies the expression of mammaglobin and cytokeratin-19 genes using quantitative RT-PCR technology to determine SLN status. Fresh SLN sections (2 mm thick) were analyzed alternatively by BLN assay or post-operative histology (haematoxylin–eosin and immunohistochemistry). The subject was considered positive when histology revealed a focus >0.2 mm.

Results

BLN assay results corroborated with histologic results in 75 out of 78 patients for an overall agreement of 96 % , a sensitivity of 92 % , and a specificity of 97 % . The positive and negative predictive values of the BLN assay were of 86 % (12/14) and 98 % (63/64), respectively. Interestingly, a statistically significant correlation was observed between the metastases' histologic size and both assay markers' expression levels as represented by cycle time to positivity (ρ ≥ 0.71, all p < 0.0001).

Conclusions

The performance of the BLN assay in identifying nodal metastases >0.2 mm was similar to that of permanent section histology, with the added advantages of an objective and rapid output that could be used for intra-operative decision to remove additional ALN.