Metallothionein isoform 3 overexpression is associated with breast cancershaving a poor prognosis

The third isoform (MT-3) of the metallothionein gene family is unique in th at It has a limited tissue distribution, is not induced by metals, has a ne uronal growth inhibitory activity, and sequesters wine more effectively und er zinc-depleted conditions, The goal of the present study was to determine whether MT-3 was absent in normal breast tissue, was overexpressed in brea st cancers, and If MT-3 overexpression would be associated with disease out come. A combination of immunohistochemistry and reverse-transcription polym erase chain reaction was used to demonstrate that the normal breast had no detectable expression of MT-3 mRNA or protein. Using immunohistochemistry, it was shown that MT-3 was overexpressed In 25 of 34 cases of breast cancer . In all cases of positive staining, MT-3 was diffusely localized to the cy toplasm, The tumors from these 34 cases were divided as to outcome based on known 5-year survival, with 20 patients being disease free at 5 years (goo d outcome) and the other 14 having recurring disease within 5 years (bad ou tcome). When analyzed for MT-3 staining, it was shown that there was a tren d for increased MT-3 immunoreactivity in the group having bad outcomes. How ever, when the tumor subgrouping was further defined on the basis of carcin oma in situ (CIS), there was a marked significant difference In MT-3 staini ng between patients with good and bad outcomes. Limited to DCIS, MT-3 stain ing was significantly increased in patients with bad outcomes compared to t hose with good outcomes. Thus, these studies demonstrate that MT-3 is overe xpressed in selected breast cancers and that overexpression is associated w ith tumors having a poor prognosis.