The absence of immunoreactivity for tissue inhibitor of metalloproteinase-1 (TIMP-1), but not for TIMP-2, protein is associated with a favorable prognosis in aggressive breast carcinoma.
OBJECTIVE
High tumor grade and lymph node positivity are associated with poor prognosis in breast carcinoma. Prognostic markers are used to define which patient groups benefit from different treatment modalities, some of which are potentially very toxic. Matrix metalloproteinases (MMPs) degrade the extracellular matrix, and type IV collagenases MMP-2 and -9 have been linked to invasive behavior of several malignancies. Tissue inhibitors of metalloproteinases (TIMPs) -1 and -2 inhibit their activity and are therefore considered to have an inhibitory effect on tumor progression. The role of TIMPs in progression of breast carcinoma is, however, still poorly known. Here the effect of TIMP-1 and -2 on survival was examined in lymph node-positive breast carcinoma patients.


METHODS
TIMP-1 or -2 was evaluated with avidin-biotin immunohistochemical staining from paraffin-embedded sections of primary breast carcinoma of 132 cases.


RESULTS
Positive staining for TIMP-1 and -2 was observed in 81 and 84% of the tumors respectively. TIMP-1 correlated to the grade of the tumor (p = 0.047). Absence of TIMP-1 protein correlated with favorable disease-specific survival of the patients with high-grade tumors. After 10 years of follow-up as high as 88% of patients with a grade 2-3, but TIMP-1-negative tumor were alive, when only 61% of the TIMP-1-positive cases in this group survived by that time (p = 0.03).


CONCLUSIONS
Our results suggest that lack of TIMP-1 protein expression is associated with a favorable prognosis in patients with node-positive high-grade breast carcinoma.
Kuvaja
Paula
P
Department of Oncology and Radiotherapy, Oulu University Hospital, Oulu, Finland.
Talvensaari-Mattila
Anne
A
Pääkkö
Paavo
P
Turpeenniemi-Hujanen
Taina
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis* / Q000276:immunology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis* / Q000276:immunology
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2