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M34 Actin Regulatory Protein Is a Sensitive Diagnostic Marker for Early- and Late-Stage Mammary Carcinomas

Department of Cell and Developmental Biology, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, New York

Purpose: At present, there is no available molecular marker that reliably detects the earliest stages of epithelial transformation in the majority of patients affected with incipient breast carcinoma. Here we introduce M34 protein, a mammalian actin filament regulatory protein, as a highly sensitive and easily detected positive cellular marker for both early and late stages of breast carcinoma.

Experimental Design: In this study, 24 human lactation duct neoplasms from postmenopausal women, including fibroadenoma, ductal carcinoma in situ, intraductal lobular papilloma, and metastatic adenocarcinoma, were analyzed for the presence of M34 protein by histochemical staining of paraffin and fresh-frozen sections.

Results: All 24 neoplasias tested positive for M34, whereas none of the 4 normal breast tissues stained for the protein. M34 identification was strongly positive for transformed epithelium in all tumor types tested. Twelve precancerous lesions of fibroadenoma (n = 4), intraductal papilloma (n = 4), and incipient ductal carcinoma in situ (n = 4) all showed high levels of M34 staining, suggesting that precancerous tumors, as well as the earliest stages of mammary carcinoma, can be sensitively detected. Furthermore, anti-M34 antibody selectively stained all 12 advanced-stage metastatic adenocarcinoma cell masses and micrometastases in axillary lymph nodes tested. Single-cell micrometastases embedded in connective tissue or lymph node parenchyma could be clearly resolved by M34 with horseradish peroxidase staining. Lymphocytes, normal ductal endothelium, and vascular endothelial cells were M34-negative, as were muscle, nerve, and adipose tissues. Low-level M34 staining was detected in connective tissue fibroblasts, macrophages, and neutrophils.

Conclusions: To our knowledge, no previously reported markers have shown high sensitivity of detection for both the earliest and most advanced stages of breast carcinoma. Consequently, M34 appears uniquely suited for diagnosis of the earliest stages of lactation duct transformation as well as for advanced-stage mammary carcinoma metastases in surgical margins and axillary lymph nodes.