Tissue-type plasminogen activator (tPA) in breast cancer: relationship with clinicopathological parameters and prognostic significance.
BACKGROUND
Tissue-type plasminogen activator (tPA) is a serine protease primarily involved in the intravascular dissolution of blood clots. High intratumoral tPA levels are associated with prognosis in several human tumors. In addition, tPA has been shown to be an estrogen-inducible protein in human breast cancer cell lines. The aim of the present study was to analyze the cytosolic tPA content in primary breast carcinomas and its potential clinical value.


METHODS
tPA was measured by a solid-phase enzyme immunoassay in tumor cytosol samples obtained from 800 patients with breast cancer. The median follow-up period was of 49.2 months.


RESULTS
Cytosolic tPA levels ranged widely in breast carcinomas (median: 3.9; range: 0.1- 315.3 ng/mg protein). tPA levels were significantly lower in large tumors, as well as in those showing poor differentiation, estrogen (ER) or PgR-negativity, aneuploidy, or a high S-phase fraction. In addition, low tPA intratumoral levels were associated with a high probability of both shortened relapse-free and overall survival in all patients and in the subgroup with node-negative tumors. However, our results did not show any significant relationship between intratumoral tPA levels and prognosis in the different subgroups of patients, stratified according to the type of systemic adjuvant therapy received (chemotherapy, tamoxifen or chemotherapy plus sequential tamoxifen).


CONCLUSIONS
The results of the present investigation indicate that low intratumoral tPA levels are associated with aggressiveness and poor prognosis in breast cancer patients. However, the study suggests that tPA levels do not predict response to systemic adjuvant therapy.
Corte
M Daniela
MD
Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain.
Vérez
Paula
P
Rodríguez
Juan Carlos
JC
Roibás
Antonio
A
Domínguez
M Luz
ML
Lamelas
M Luz
ML
Vázquez
Julio
J
García Muñiz
José L
JL
Allende
M Teresa
MT
González
Luis Ovidio
LO
Fueyo
Antonio
A
Vizoso
Francisco
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D003600:Cytosol / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D013030:Spain / Q000453:epidemiology; D018709:Statistics, Nonparametric; D015996:Survival Rate; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D014408:Biomarkers, Tumor; D010959:Tissue Plasminogen Activator