Avtor/Urednik		Lah, Tamara T; Kos, Janko; Blejec, Andrej; Frkovič-Grazio, Snežana; Golouh, Rastko; Vrhovec, Ivan; Turk, Vito
Naslov		The expression of lysosomal proteinases and their inhibitors in breast cancer: possible relationship to prognosis of the disease
Tip		članek
Vir		Pathol Oncol Res
Vol. in št.		Letnik 3, št. 2
Leto izdaje		1997
Obseg		str. 89-99
Jezik		eng
Abstrakt		Proteolytic enzymes have been proposed as new biological prognostic indicators to facilitate decisions about treatment of breast cancer patients following surgery. We reported earlier that the activities of cysteine proteinases (CP), cathepsin (Cat) B and cathepsin (Cat) L and the expression of stefin A might be associated with breast tumor progression and prognosis. Here, the protein concentrations of Cats D, B and L and stefin A have been measured in a series of 60 matched pairs of breast tumours and control adjacent tissues, using ELISAs developed in our laboratory. Median tumor concentrations of Cat D (47 pm/mg), Cat B (222 ng/mg) and Cat L (88 ng/mg) were significantly (p<0.0005) increased by 7 fold, 27 fold and 6 fold, respectively. Much greater increases in the activities of Cat B (63 fold) and of Cat L (274 fold) were found, indicating enhanced activation of cysteine proteinases in tumors, due either to proteolytic activation of proCat B and proCat L and/or to a decrease in specific endogenous cystatins. However, the 1.6-fold decreased (p<0.0001) levels of inhibition by cystatins could not be entirely responsible for more than 100-fold increased ratio of CP: cystatins activity. Moreover, stefin A was either increased or decreased in tumor samples, resulting in a 1.4-fold median increase in tumors. Comparing the biological parameters with the established histo-pathological prognosticators, we found that the increased protein concentration of Cat B was associated with lymph node involvement (p<0.009) and higher stage (p<0.003), and both Cat B and Cat L activities were more increased in high grade tumours (p<0.05). Survival analysis revealed that stefin A was the most significant prognostic factor for disease-free (p<0.008) and overall survival (p<0.02), followed by increased Cat B activity and protein concentration. (Abstract truncated at 2000 characters).
Deskriptorji		BREAST NEOPLASMS CATHEPSINS CYSTEINE PROTEINASE INHIBITORS CYSTEINE PROTEINASES CYSTATINS CATHEPSIN B CATHEPSIN D ENZYME-LINKED IMMUNOSORBENT ASSAY LYSOSOMES NEOPLASM STAGING PROGNOSIS NEOPLASM METASTASIS