Expression levels of nm23-H1 were evaluated in a variety of normal, benign and malignant breast tissues by Northern and slot blot. Tissues from 153 patients presenting with palpable breast lesions were studied: 132 primary infiltrating breast cancers, 9 pure duct carcinoma in situ lesions, a phyllodes tumor, 9 benign lesions and 2 local recurrences of carcinoma. In addition to lesional tissue, 49 samples of macroscopically normal breast tissue, 37 axillary lymph nodes and 9 samples from patients undergoing cosmetic reduction mammoplasty were studied. Sets of normal breast tissue, primary tumor and lymph node tissue from individual patients were available for comparison in 37 cases. A wide range of gene expression was detected in the various tissue types. The highest levels of expression were detected in malignant samples with in situ carcinomas being associated with the highest levels of gene expression. The expression levels of nm23-H1 in normal breast tissue were lower than the corresponding tumors from the same patients (p<0.0005). Benign breast lesions (including 6 fibroadenomas) had levels of gene expression approximating those of the normal tissue samples. Normal axillary lymph nodes had significantly lower levels of nm23-H1 expression than nodes with metastatic deposits (p<0.03). No significant association was observed between nm23-H1 expression levels and axillary node status in patients With infiltrating carcinoma, although there was a slight trend toward lower nm23-H1 mRNA levels in the node negative group. Some special tumor types known to metastasize infrequently (tubular, tubulo-lobular carcinoma) had low levels of expression, whilst others (colloid carcinoma) exhibited high levels of expression. Comparison of samples of primary tumor, surrounding normal breast and metastatic node deposits in individual patients showed no clear trends in gene expression between these tissue types. The validity of nm23-H1 as a marker of metastatic potential is questioned on the basis of these results. The higher levels of expression observed in malignant tissue suggest that nm23-H1 may be involved in tumorigenesis, but clear evidence for this, and the mechanisms by which the gene may influence tumor biology, remain to be determined.
