Metallothionein Isoform 3 Overexpression Is Associated with Breast Cancers Having a Poor Prognosis

The third isoform (MT-3) of the metallothionein gene family is unique in that it has a limited tissue distribution, is not induced by metals, has a neuronal growth inhibitory activity, and sequesters zinc more effectively under zinc-depleted conditions. The goal of the present study was to determine...

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Veröffentlicht in:The American journal of pathology Jg. 159; H. 1; S. 21 - 26
Hauptverfasser: Sens, Mary Ann, Somji, Seema, Garrett, Scott H., Beall, C. Larry, Sens, Donald A.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Bethesda, MD Elsevier Inc 01.07.2001
ASIP
American Society for Investigative Pathology
Schlagworte:
Adult
Aged
Aged, 80 and over
Biological and medical sciences
Breast Neoplasms - metabolism
Breast Neoplasms, Male - metabolism
Carcinoma in Situ - metabolism
Carcinoma, Ductal, Breast - metabolism
Carcinoma, Ductal, Breast - pathology
Female
Gynecology. Andrology. Obstetrics
Humans
Immunohistochemistry
Male
Mammary gland diseases
Medical sciences
Middle Aged
Neoplasm Invasiveness
Neoplasm Recurrence, Local
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Prognosis
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Short Communications
Survival Analysis
Tissue Distribution
Tumors
Human
Immunohistochemistry
Pathology
Mammary gland diseases
Molecular form
Carcinoma
Prognosis
Gene overexpression
Malignant tumor
Mammary gland
Gene expression
Metallothionein
ISSN:0002-9440, 1525-2191
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Zusammenfassung:The third isoform (MT-3) of the metallothionein gene family is unique in that it has a limited tissue distribution, is not induced by metals, has a neuronal growth inhibitory activity, and sequesters zinc more effectively under zinc-depleted conditions. The goal of the present study was to determine whether MT-3 was absent in normal breast tissue, was overexpressed in breast cancers, and if MT-3 overexpression would be associated with disease outcome. A combination of immunohistochemistry and reverse-transcription polymerase 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 cytoplasm. 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 (good outcome) and the other 14 having recurring disease within 5 years (bad outcome). When analyzed for MT-3 staining, it was shown that there was a trend for increased MT-3 immunoreactivity in the group having bad outcomes. However, when the tumor subgrouping was further defined on the basis of carcinoma in situ (CIS), there was a marked significant difference in MT-3 staining between patients with good and bad outcomes. Limited to DCIS, MT-3 staining was significantly increased in patients with bad outcomes compared to those with good outcomes. Thus, these studies demonstrate that MT-3 is overexpressed in selected breast cancers and that overexpression is associated with tumors having a poor prognosis.
Bibliographie:ObjectType-Article-1
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content type line 23
ISSN:0002-9440
1525-2191
DOI:10.1016/S0002-9440(10)61668-9