Immunohistologic evaluation of invasion-associated proteases in breast carcinoma.
Immunostaining of two invasion-associated proteolytic enzymes, cathepsin D (CD) and urokinase-type plasminogen activator (uPA), was assessed in cryostat sections of 86 stage-heterogeneous breast carcinomas using monoclonal antibodies. Most tumors displayed a focal and/or heterogeneous staining pattern. Overall, staining was more frequent in host-derived stromal and inflammatory cells (uPA 54%, CD 89%) than neoplastic epithelium per se (uPA 24%, CD 70%). Intense (i.e., 2+) stromal, but not neoplastic, CD was significantly correlated with nodal or systematic metastases (node negative--10% versus node positive/systemic--33%, p = 0.04). Further, cumulative staining of more than one enzyme (CD + uPA) or more than one tumor component (stroma + epithelium) correlated with metastatic disease (no metastases--35% versus metastatic--72%, p = 0.005). Neither stromal nor epithelial CD alone was significantly correlated with short-term recurrence free survival, however additive CD staining (i.e., stromal + epithelial) was strongly predictive, overall (both + -75% recurred versus both weak/negative--16% recurred, p = 0.0004) and in node positive patients (p = 0.02). We conclude that (a) enzymes putatively mediating extracellular matrix dissolution may be derived from multiple sources and (b) the metastatic capacity and/or clinical aggressiveness of breast carcinomas may reflect overall proteolytic enzyme expression, suggesting that cooperative enzyme interaction may be required for invasive growth and/or metastasis.
Visscher
D W
DW
Department of Pathology, Harper Hospital, Detroit, Michigan.
Sarkar
F
F
LoRusso
P
P
Sakr
W
W
Ottosen
S
S
Wykes
S
S
Crissman
J D
JD
D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000628:therapy; D002402:Cathepsin D / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
D014568:Urokinase-Type Plasminogen Activator; D002402:Cathepsin D