EVALUATION OF THE EXPRESSION LEVELS OF NM23-H1 MESSENGER-RNA IN PRIMARY BREAST-CANCER, BENIGN BREAST DISEASE, AXILLARY LYMPH-NODES AND NORMAL BREAST

Expression levels of nm23-H1 were evaluated in a variety of normal, be nign and malignant breast tissues by Northern and slot blot. Tissues f rom 153 patients presenting with palpable breast lesions were studied: 132 primary infiltrating breast cancers, 9 pure duct carcinoma in sit u lesions, a phyllodes tumor, 9 benign lesions and 2 local recurrences of carcinoma. In addition to lesional tissue, 49 samples of macroscop ically normal breast tissue, 37 axillary lymph nodes and 9 samples fro m patients undergoing cosmetic reduction mammoplasty were studied. Set s of normal breast tissue, primary tumor and lymph node tissue from in dividual patients were available for comparison in 37 cases. A wide ra nge of gene expression was detected in the various tissue types. The h ighest levels of expression were detected in malignant samples with in situ carcinomas being associated with the highest levels of gene expr ession. 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 ax illary lymph nodes had significantly lower levels of nm23-H1 expressio n than nodes with metastatic deposits (p<0.03). No significant associa tion was observed between nm23-H1 expression levels and axillary node status in patients With infiltrating carcinoma, although there was a s light trend toward lower nm23-H1 mRNA levels in the node negative grou p. Some special tumor types known to metastasize infrequently (tubular , tubulo-lobular carcinoma) had low levels of expression, whilst other s (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 ex pression between these tissue types. The validity of nm23-H1 as a mark er 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 biolog y, remain to be determined.