Immunohistochemical localization of metallothionein in human breast cancer in comparison with cathepsin D, stromelysin-1, CD44, extracellular matrix components, P53, Rb, C-erbB-2, EGFR, steroid receptor content and proliferation.
Metallothionein (MT) is a low molecular weight, cysteine-rich, zinc-binding protein that may have a function in cellular repair processes, growth and differentiation. Using a monoclonal antibody (E9) to metallothionein, we investigated the immunohistochemical expression of MT in routinely fixed and paraffin-embedded tissue from 98 cases of female breast carcinomas. The MT expression was studied in comparison with the expression of the basement membrane (BM) antigens (type IV collagen, laminin), fibronectin, cathepsin D, adhesion molecule CD44, p53 protein, the pRb, c-erbB-2 oncoprotein, EGFR, stromelysin-1, proliferation indices (Ki-67, PCNA), steroid receptor content as well as with other conventional clinicopathological parameters of breast cancer. Strong MT expression was observed in the majority of tumour cells in 18.4% of tumours, focal MT positivity in 13.3% and almost complete lack of MT expression in 68.4% of cases (mean value 33.36 +/- 26.36). The MT expression in carcinoma cells was strongly associated with the DCIS component of the tumour (p < 0.0001). High values of MT were correlated with low steroid receptor status (p = 0.08 for ER receptor and p = 0.019 for PgR receptor content). MT positive cases were correlated with stromelysin-1 expression (p = 0.059) and cathepsin D (p = 0.058). These findings suggest that MT expression is characteristic of the early phase of breast carcinogenesis, possibly regulated by hormones, and could be a new potential prognostic marker in breast cancer.
Ioachim
E
E
Pathology Department, Medical School, University of Ioannina, Greece.
Kamina
S
S
Demou
A
A
Kontostolis
M
M
Lolis
D
D
Agnantis
N J
NJ
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000648:ultrastructure; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000473:pathology / Q000648:ultrastructure; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D018275:Carcinoma, Lobular / Q000737:chemistry* / Q000473:pathology / Q000648:ultrastructure; D002402:Cathepsin D / Q000032:analysis; D002455:Cell Division; D066246:ErbB Receptors / Q000032:analysis; D016326:Extracellular Matrix Proteins / Q000032:analysis; D005260:Female; D005629:Frozen Sections; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000032:analysis; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D008668:Metallothionein / Q000032:analysis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016160:Retinoblastoma Protein / Q000032:analysis; D013347:Subcellular Fractions / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D002402:Cathepsin D; D066246:ErbB Receptors; D016326:Extracellular Matrix Proteins; D019394:Ki-67 Antigen; D019278:Matrix Metalloproteinase 3; D008668:Metallothionein; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53