Detection of MAGE-A3 in breast cancer patients’ sentinel lymph nodes

Abstract

SummaryThe detection of occult metastatic breast cancer cells by RT-PCR is limited by the poor specificity of most tumour mRNA markers. MAGE-A3 is a highly specific tumour mRNA marker that is not expressed in non-cancer cells. This study assesses MAGE-A3 mRNA as a molecular marker for the detection of tumour cells in the sentinel lymph nodes (SLN) of breast cancer patients. Serial frozen sections of SLN (n = 121) were obtained from 77 AJCC (American Joint Committee on Cancer) Stage I-IIIA breast cancer patients. MAGE-A3 mRNA analysis of SLN was performed by RT-PCR and Southern blot analysis. Tumour cells were detected in 48 of 121 (40%) SLN from 77 patients by H&E or IHC staining, and 35 of 77 (45%) patients, overall, had histopathologically (H&E and/or IHC) positive SLN. Among histopathologically negative SLN, 28 of 73 (38%) SLN were MAGE-A3 mRNA positive by RT-PCR. Overall, 41 of 77 (53%) patients and 50 of 121 (41%) SLN were positive for MAGE-A3. MAGE-A3 mRNA expression in the SLN occurred more frequently with infiltrating lobular carcinoma (P < 0.001) than with infiltrating ductal carcinoma, adding further evidence of possible phenotypic differences between these 2 subtypes of breast cancer. Due to its high specificity, MAGE-A3 mRNA is a potentially useful marker for detecting breast cancer cells in the SLN. One half of breast tumours expressed MAGE-A3 mRNA, which has important potential implications for antigen-specific targeted immunotherapy.

MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition

“…Also, MAGE-A-positive cases were often with high histological grade and metastatic axillary lymph nodes, which strengthened the association between MAGE-A and cancer progression. According to some studies, MAGE-A proteins have to do with negative hormone receptor status, high histologic grade [37,39], large tumor size (≥2cm) [36], positive sentinel lymph nodes (SLN) [40], high Ki-67 score [27] and HER-2 negativity. Notably, MAGE-A expression is contributed to unfavorable outcomes and cancer development.…”

Detection of lymph node metastases of papillary thyroid cancer—comparison of the results of histopathology, immunohistochemistry and reverse transcription-polymerase chain reaction—a preliminary report

“…They have the advantage of a higher sensitivity and the possibility of researching not only single sections of a lymph node in a single examination. RT-PCR is a rapidly developing technique, which has been successfully applied to the investigation of micrometastases of many solid, malignant, tumours such as: gastric cancer, colorectal cancer, prostate cancer, breast cancer, pancreatic cancer [36][37][38][39][40][41][42][43][44]. In gastrointestinal cancers, detection of micrometastases by molecular methods, in histopathologically negative lymph nodes, was the most important factor indicating a possibility of local relapse and the need for more aggressive treatment [35][36][37].…”

Sentinel lymph node mapping for primary breast cancer

“…The study additionally revealed that overexpression of one or more tumor mRNA markers in the SN correlated with poor prognostic clinicopathologic factors. In another study from our institution, Wascher et al [24] used MAGE-A3, a highly specific tumor mRNA marker not expressed in non-cancer cells, as a single tumor marker in RT-PCR with high specificity. More recently, Gillanders et al [25••] provided further evidence that multimarker RT-PCR is a valid surrogate for detection of occult micrometastasis in the axillary lymph node.…”