Perioperatory kinetic evaluation of tumor markers in breast and colorectal carcinoma.
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Antigens, Tumor-Associated, Carbohydrate↗
Biomedical subjects
M Gion
Publications and source records attributed to M Gion.
Tumor markers in squamous cell carcinoma of esophagus: immunometric assay in cytosol and membrane fraction.
Carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), ferritin, and the monoclonal antibody-detected tumor-associated antigens CA19.9 and CA50 were measured by radioimmunoassay in tissue fractions of carcinoma and normal esophageal mucosa from 59 patients with untreated primary squamous cell carcinoma of the esophagus. Tumor markers were measured in cytosol (118 samples) and in a membrane-enriched fraction (32 samples). CEA, TPA and ferritin were detected in almost all the cytosol samples evaluated, CA19.9 and CA50 in 66% and 50% of cases respectively. Ferritin was significantly higher in carcinoma than in normal mucosa. The cytosol concentrations of CEA, TPA, CA19.9 and CA50 were not significantly different in carcinoma and normal tissue. Concentrations of CEA, CA19.9 and CA50 in the membrane fraction tended to be higher in normal tissue than in carcinoma, whereas the cytosol-to-membrane ratio was significantly higher in carcinoma. For CEA, CA19.9 and CA50, the phenotypic pattern of the malignant transformation seems to involve a different intracellular distribution rather than a quantitative change. No correlations were found between tissue and serum concentrations of the tumor markers, the former being related to the phenotypic characteristics of the tumor, the latter to the tumor burden.
Adult↗
Evaluation of CA15/3 serum levels in breast cancer patients.
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Antigens, Neoplasm↗
[Determination of cytoplasmic estrogen and progesterone receptors in breast carcinoma: comparison of a histochemical and a radiometric method].
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Breast Neoplasms↗
Comparison between western blotting, immunohistochemical and ELISA assay for p185neu quantitation in breast cancer specimens.
The protein encoded by erbB2 oncogene was evaluated by three different methodological approaches (Western blotting, ELISA and immunohistochemistry) in 147 breast cancer specimens. A highly significant correlation was found between Western blotting and ELISA results (p < 0.001). The data from ELISA and Western blotting were categorized as negatives (-), low-overexpressing (+) and high-overexpressing (++). Immunohistochemical results were classified as (-) or (+) according to the absence or the presence of specific staining. Overall positive cases (+ and ++) were 42.2% by Western blotting and 51% by ELISA, while (++) cases were 23.8% and 25.2% respectively. Histochemical staining was found in 29.8% of cases. The two by two evaluation of the assays showed a close association (chi2, p < 0.0001). In particular, the comparison between both ELISA and Western blotting with immunohistochemistry showed concordance rates of 78.9% for ELISA and 83.1% for Western blotting considering the + and ++ cases as a single group. When only the ++ cases were considered as positive, the overall agreement rises to 93.3% and 89.1% respectively. From these preliminary data we conclude that p185 values obtained with the three evaluated methods are possibly superimposable. Nevertheless, the biochemical methods seem to identify an intermediate p185 expression group, whose clinical meaning should be investigated.
Biomarkers, Tumor↗
Biochemical parameters for prognostic evaluation in patients with breast cancer.
We evaluated the prognostic value of tissue polypeptide antigen (TPA), cathepsin D and pS2 in 267 patients operated for primary breast cancer. Cathepsin D, pS2 and cytosol TPA were independent of each other and of N, T, estrogen (ER) and progesterone (PgR) receptors. Cathepsin D was the best prognostic indicator for disease-free survival and pS2 for overall survival. The simultaneous evaluation of the three parameters was an effective discriminator between high and low risk patients in both N- and N+. Considering that cathepsin D, pS2 and cytosol TPA can be easily measured with reliable methods in small amounts of tissue, we conclude that they are a promising panel of biochemical parameters suitable for the assessment of the risk of relapse in patients with breast cancer.
Analysis of Variance↗
Dynamic use of tumor markers, rationale-clinical applications and pitfalls.
The dynamic evaluation of tumor markers is a promising area of investigation which is expected to provide clinical information when serial samples are available from the same patient. This is feasible in the post-operatory evaluation, during the follow-up after the treatment for to the primary tumor and in the monitoring of the treatment for metastatic disease. Variations among serial samples may be assessed using both empirical and mathematical approaches. Empirical approaches rely on overcoming a given percentage usually chosen on the base of arbitrary decisions. Mathematical approaches include the actual half-life, the doubling time, a dose/time regression analysis and the calculation of the critical difference. The two former are currently used in clinical practice whereas the two latter are still matter of investigation. As concerns the assessment of the radicality of the surgery for the primary tumor, the serum markers are used in germ cell tumors and in prostate cancer. The half-life of the markers is the decision criteria used in germ cell cancers, while in prostate cancer PSA is expected to be undetectable more than 30 days after the radical prostatectomy. Tumor markers are currently used during the follow-up of several malignancies after the treatment for primary tumor. Although several samples are available, decision criteria are still based on positive/negative cut-off values in several instances. Promising dynamic approaches are under investigation and are expected to lead to earlier and probably more accurate information concerning the disease progression. A critical point still under debate is the actual impact of tumor markers on patients' survival in malignancies incurable when metastatic, such as colorectal cancer and breast cancer. This matter urgently demands perspective clinical studies. Finally, the dynamic use of tumor markers is now commonly applied in the monitoring of the therapy for metastatic malignancies. In this clinical setting mathematical criteria are used for ovarian and and germ cell tumors with promising results. Nevertheless, the use of empirical criteria, namely the percentage of variation between two consecutive samples, is successfully used for the monitoring of the therapy of metastatic breast cancer. In conclusion, when several samples are available from an individual patient they may be evaluated according to dynamic criteria instead of referring to a conventional positive/negative cut-off point. Although mathematical decision criteria are expected to provide more reliable data, empirical approaches are used as well and provide useful information in decision making.
Biomarkers, Tumor↗
ErbB2 assay in breast cancer: possibly improved clinical information using a quantitative method.
ErbB2/neu protein (p185) expression was evaluated by ELISA in 115 breast cancer specimens. Distribution was subdivided in quartiles and showed a distinct behaviour in comparison with both clinico-biological parameters and clinical outcome. In particular, intermediate concentration groups showed a significantly better disease-free survival than the low and high concentration groups (p = 0.02). We classified the patients as "low risk" (64 samples with p185 concentrations between 2150 and 30000 U/mg of proteins) and "high risk" on the basis of the results of the multivariate analysis. The p185 grouped as described showed a significant relationship with the disease free survival in multivariate analysis. Although the data must be considered as preliminary, they suggest the possibility of identifying more appropriately the high risk patients through the biochemical determination of p185.
Breast Neoplasms↗
Quantitative chemiluminescent immunoassay of p53: prognostic significance in 220 node-negative breast cancer tissue.
The prognostic and predictive role of p53 overexpression in breast cancer samples is usually investigated by using molecular biology or immunohistochemical methods. However, the results are to date controversial, and this is in part due to the methodological pitfalls of both the methods. To study the possibility of overcoming, at least in part, these problems we evaluated a commercially available chemiluminescent immunoassay with which the p53 concentrations of 220 specimens from node negative breast cancer were determined. The assay showed good analytical performance and found detectable levels in 84.7% of cases (median 0.22 ng/mg of proteins, range 0-50 ng/mg of proteins). p53 has been found inversely correlated with estrogen receptors and directly correlated with cathepsin D. The prognostic role of p53 was evaluated in two different ways: a) two previous studies (Borg et al 1995, DeWitte et al. 1996) using the same method found almost 30% of samples had significantly shorter DFS and OS. We subdivided our cases in order to identify the same positivity rate and to verify if the previous cathegorizations were effective also in our patient series. We confirmed the independent association with DFS (p = 0.006) and OS (p = 0.0005); b) considering that any categorization of quantitative parameters could cause a loss of clinical information, we also evaluated p53 as a continuous variable. Multivariate analysis showed a significant quantitative relationship between p53 and both disease free (p = 0.026) and overall survival (p = 0.02).
Aged↗
Impact of steroid receptors, pS2 and cathepsin D on the outcome of N+ postmenopausal breast cancer patients treated with tamoxifen.
In spite of the complexity of the biological basis of the hormonal regulation of breast cancer, clinical studies tend to simplify the information by mainly categorizing continuous variables related to hormonal status and not considering the interactions between variables. The present study was planned to examine the presence of an interaction between cathepsin D (Cath-D) and pS2 in patients treated with adjuvant tamoxifen in a homogeneous subset of node-positive postmenopausal patients and to evaluate the contribution of the interaction to the predictive ability of the model. Steroid receptors (ER and PgR) were measured in cytosol using the dextran-coated charcoal method, while Cath-D and pS2 were determined using commercially available immunoradiometric assays. The prognostic role of each variable and their joint effect were investigated using a Cox regression model. Biological variables were analyzed as continuous and when their prognostic relationship did not seem linear, a restricted cubic spline regression smoothing approach was adopted. The logarithm of hazard showed a linear relationship with the log(ER), while it i) remained almost constant up to about 20 fmol/mg and subsequently decreased for PgR; ii) was almost constant up to about 50 pmol/mg and subsequently decreased for Cath-D; iii) decreased for increasing log(value) up to about 33 ng/mg and subsequently increased for pS2. In the multivariate analysis both PgR and the interaction between pS2 and Cath-D retained a significant prognostic role. For low values of pS2, the prognosis worsened with the increase in Cath-D levels and this relationship reversed for high values of pS2. From the results of the present study we can conclude that i) a significant interaction between Cath-D and pS2 was found in this case series; ii) the prognostic relationship should not be underestimated in clinical decision making; iii) a predictive score obtained considering the contribution of PgR, pS2 and Cath-D could be useful for clinical use.
Age Factors↗