Detection of hepatocyte growth factor/scatter factor receptor (c-Met) in axillary drainage after operations for breast cancer using reverse transcriptase-polymerase chain reaction

Abstract

Background: The diverse biological effects of hepatocyte growth factor/scatter factor (HGF/SF) are mediated by c-Met, which is preferentially expressed on epithelial cells. Met signaling has a role in normal cellular activities, and may be associated with the development and progression of malignant processes. In this study we examined whether Met can be detected in the axillary drainage from patients who underwent conservative operations for breast cancer, and its prognostic significance.

Methods: Thirty-one consecutive patients with invasive ductal carcinoma of the breast suitable for breast-conserving treatment were studied. The output of the drain that had been placed in the axilla during the operation was collected, and the presence of Met and beta-actin were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) assays. The data were compared with the pathological features of the tumor and the axillary lymph nodes, and with the estrogen receptor and progesterone receptor status.

Results: RT-PCR of the axillary lymphatic drainage was positive for Met in 23 (74.2%) of the patients. Positive assays were correlated with increasing tumor size and grade, with capillary and lymphatic invasion, and with lymph node metastasis (P < 0.02, for all comparisons). All 12 patients with axillary lymph node metastases had positive assays for Met, compared with 57.9% of patients without lymph node metastases. All five patients with tumor involvement in the margins of the resection had positive assays for Met in their lymphatic fluid, compared with 18 of 26 positive assays (69.2%) for patients without involved margins (P < 0.04). Finally, Met showed negative correlations with positivity for estrogen receptor and progesterone receptor (P < 0.02).

Conclusion: Met can be detected in the axillary fluids of patients with breast cancer and its expression in the axillary drainage may have potential as a prognostic factor. This finding might be relevant to therapeutic considerations, because a positive assay for Met in histologically node-negative patients might point to the need to search for node microinvasion or involvement of the excision margins with tumor.

Figure 1

Reverse transcriptase–polymerase chain reaction (RT–PCR) amplification of Met and β-actin mRNA obtained from lymphatic fluids from women with breast cancer. Met and β-actin expression were examined by RT–PCR, and the results of agarose-gel electrophoresis of some of the patients are shown.