The lysosomal cysteine proteinase cathepsin B has been implicated in the progression of various human tumors including ovarian cancer. Included in this study were 63 patients with epithelial ovarian carcinoma. Follow-up information (median follow-up period 7 years) was available for all patients, among whom 42 (66.7%) had relapsed and 32 (50.8%) had died. The immunohistochemistry method was adopted for the detection of cathepsin B using paraffin embedded specimens. Results were compared to clinico-pathological data. Statistical analysis showed cathepsin B expression to be significantly associated with the stage of disease, debulking success and interestingly, with progesterone receptors. It was also inversely related to progression-free survival (PFS) and overall survival (OS). Accordingly, cathepsin B can be regarded as unfavorable and as an independent tumor marker for progression-free survival and overall survival in ovarian cancer patients with long follow-up.
Summary C-myc and c-erbB-2 amplification and/or overexpression as well as total cathepsin-D (CD) concentration have been reported to be associated with poor prognosis in breast cancer. The prognostic significance, however, remains somewhat controversial, partly because of discrepancies among the different methodologies used. We determined the amplification and overexpression of c-myc oncogene in 152 breast cancer patients and examined its prognostic value in relation to c-erbB-2 amplification and overexpression, high concentration of CD (≥ 60 pmol mg -1 protein) and standard clinicopathological prognostic factors of the disease. High CD concentration, as well as c-myc amplification and overexpression, proved to be the best of the new variables examined for prediction of early relapse (ER; before 3 years). After multivariate analysis only CD remained significant, which suggests that the prognostic power of these variables is similar. Using univariate analysis we proved that c-myc amplification and overexpression were highly significant for disease-free survival (DFS) (P = 0.0016 and P = 0.0001 respectively) and overall survival (OS) (P < 0.0001 and P = 0.0095 respectively), although by multivariate analysis c-myc overexpression was statistically significant only for DFS (P = 0.0001) and c-myc amplification only for OS (P = 0.0006). With regard to c-erbB-2, only its overexpression appeared to be significant for DFS and OS, although after multivariate analysis its prognostic power was weaker (P = 0.030 and P = 0.024 respectively). c-myc amplification and overexpression exhibited a tendency for locoregional recurrence (LRR) (P = 0.0024 and P = 0.0075 respectively), however, their prognostic value was lower after multivariate analysis and only CD remained significant. © 1999 Cancer Research Campaign Keywords: c-myc; c-erbB-2; cathepsin-D; early relapse; relapse-free survival; overall survival; locoregional recurrence; breast cancer 1385British Journal of Cancer (1999) 81(8), 1385-1391© 1999 Cancer Research Campaign Article no. bjoc.1999 Received 15 down-regulated the expression of c-erbB-2 and this effect was reversed by anti-oestrogens. It has been hypothesized that the activation of the two genes might share the same metabolic pathway; in fact, the c-erbB-2 gene has been identified as a cellular target for negative regulation by (Suen and Hung, 1991), whereas c-erbB-2 tyrosine kinase-mediated signals seem to down-regulate the immediate-early genes (Sistonen et al, 1990).To express its full potential in systemic disease, however, the gene may have to act in concert with other events which also render the cell capable of metastasizing. Tumours with activated c-erbB-2 show several characteristics of the aggressive phenotype and are implicated in early relapse and shortened overall survival (Allred et al, 1998;Sjogren et al, 1998). One of the molecular mechanisms involved in the process of metastasis may be overproduction of proteases that degrade the basement membrane and the extracellular matrix (Rochefort, 1...
Despite the advances in the medical care of colorectal carcinoma patients, the prognosis has improved only marginally over recent decades. Thus, additional prognostic indicators would be of great clinical value to select patients for adjuvant therapy. In the present study, the antigen levels of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1, and their immunohistochemical staining were compared in paired colorectal tumor (n = 64) and background colon tissue of the same patients with clinical and pathological staging. The antigen levels, measured with an ELISA method, were found to be significantly higher in cancer tissue (mean 1.92 ng/mg protein for uPA and 7.08 for PAI-1) than in corresponding normal mucosa (0.29 ng/mg protein for uPA and 1.11 ng/mg protein for PAI-1). There was a positive correlation between uPA and PAI-1 antigen levels and clinicopathological parameters such as grade (p < 0.001 and p = 0.01, respectively), while for Dukes’ stage, only PAI-1 correlated positively (p = 0.018). Nodal status correlated positively with uPA but not with PAI-1 antigen levels. Immunohistochemical localization of both antigens was observed mainly in cancer cells and much less in stromal cells. Staining intensity increased from adenoma to adenocarcinoma. The degree of staining was associated with grade, Dukes’ stage and nodal status for uPA (p < 0.001, p = 0.002, p < 0.001, respectively) and only with grade for PAI-1 (p = 0.007).
We describe, here, a rapid flow cytometry technique for the detection and quantification of estrogen (ER) and progesterone (PgR) receptors in several human cell lines and in clinical samples obtained from breast cancer tumors. ER and PgR quantitation can be very useful in patients with breast cancer as their role in diagnosis and prognosis is well established. However ligand binding assays and immunohistochemical assays are difficult to measure heterogeneity in individual cells. On the other hand, flow cytometry is a convenient tool for quantification in individual cells. Flow cytometric results with breast cancer cell lines and clinical samples were compared to those obtained by quantitative biochemical ER and PgR performed by the standard dextran-coated charcoal biochemical assay. The latter assay is affected by the level of endogenous steroids. This is also the case in the routine measurement of ER/PgR in patient's tumor cells whereby estradiol molecules in patient's serum produced negative or low values in the biochemical assay. The mAbs used in our flow cytometric method bind to their specific ER or PgR independently of whether they are preoccupied by their ligands and they produce reliable results. With the use of beads calibrated in MESF (Molecules of Equivalent Soluble Fluorochrome) units, the ER and PgR can be measured on a per cell basis. The flow cytometric method showed a strong correlation with biochemical receptor assessments of either ER alpha (ER alphaDCC, r = 0.918, p = 0.073) or PgR (PgRDCC, r = 0.75, p = 0.001). This study demonstrates that ER alpha and PgR can be detected by flow cytometry on a per cell basis in intact cells, and can be quantitated reliably in terms of MESF without the limitations of competition with serum's estradiol molecules.
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