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M Gion

Publications and source records attributed to M Gion.

At least 91 records · Page 5Linked to original sources
PubMedDate not supplied

Clinical profile of a new monoclonal antibody-based immunoassay for tissue polypeptide antigen.

Our preliminary evaluation of a new monoclonal antibody-based assay for tissue polypeptide antigen (TPA) has shown it to be clinically equivalent to the polyclonal antibody-based assay for TPA. The new assay (TPA-M) employs three monoclonal antibodies to epitopes on cytokeratins 8, 18 and 19. This multicenter, multinational study included 266 patients with newly diagnosed carcinomas of the lung, breast, large bowel and urinary bladder. TPA values from the two assays were compared with three other cytokeratin markers (TPS, CYFRA 21-1 and TPACyk) and with the established reference markers for these malignancies (CEA and NSE for lung, CA 15-3 for breast, CEA and CA 19-9 for colorectal tumors). Analysis of receiver operating characteristic (ROC) curves in lung, colorectal and bladder cancer showed similar sensitivities for the two assays, ranging from 50% to 80% with a specificity of 95%. In breast cancer all the markers studied showed poor sensitivity. However, TPA determination by either method could discriminate advanced stage (stages III and IV) from early stage disease (stages 0 to II). TPA showed similar discriminating ability in bladder cancer. On the basis of the results obtained in our patient series, it seems that of the cytokeratin markers studied, TPA and TPA-M are the most sensitive and offer a wide range of clinical applications.

Antibodies, Monoclonal↗
PubMedDate not supplied

Third-generation PSA: ultrasensitive or ultraprecise assay?

The ultrasensitive PSA assay has been recently acknowledged as a useful tool for the monitoring of patients prostatectomized for prostatic cancer. We have evaluated a commercially available ultrasensitive PSA assay (Immulite Third Generation PSA-DPC-Los Angeles CA) in comparison with the routinely used PSA (Immulite PSA-DPC-Los Angeles CA). When evaluated with different approaches, the analytical sensitivity of ultrasensitive PSA ranged between 0.0029 and 0.0038 ng/ml. The biological detection limit was 0.0098 ng/ml. Dilution of samples with low PSA levels showed a good recovery (from 88 to 113%) up to 1:128 dilution factor (final PSA levels ranging from 0.004 to 0.016 ng/ml in different samples). The assay precision was excellent in the low dose range, the highest interassay interadjustment CV among replicates being 5.84% when assaying serum samples with PSA lower than 1.0 ng/ml. Besides its role in the follow-up of prostatectomized patients, the evaluated ultrasensitive PSA could be reliably used for the detection of clinically meaningful PSA variations in the low dose range, and it could therefore be a candidate for the assessment of PSA velocity.

Aged↗
PubMedDate not supplied

Cathepsin D versus other prognostic factors in breast cancer. Results and controversies of a multicenter study on 2575 cases.

The aim of this study was the survey of cathepsin D determination in a large group of patients enrolled at several centers, under the coordination of the Italian Committee for Quality Control in the Oncological Laboratory. Cathepsin D was measured with the same methodology, under control of an intra and interlaboratory quality control program, in order to verify the comparability of cathepsin D results from different institutions and to analyze the frequency of cathepsin D positive cases in subgroups of patients stratified according to other prognostic parameters. This retrospective study included 2575 patients with primary breast cancer evaluated in 10 institutions. Cytosol from tumor tissue was the substrate for biochemical cathepsin D, estrogen receptor and progesterone receptor determination, with an interlaboratory quality control survey provided by the E.O.R.T.C. Receptor Group and the Italian Committee for Quality Control in the Oncological Laboratory. The results of the present study can be summarized as follows: 1) Cathepsin D is independent of menopausal status; 2) In spite of standardization of tissue handling and assay methods, different results may be obtained by different institutions. It is therefore essential that each laboratory calculates its own positive/negative cutoff values prior to any routine clinical use of the parameter. This should be a serious consideration when a multicenter study is planned.

Adult↗
PubMedDate not supplied

The prognostic significance of increasing marker levels in metastatic breast cancer patients with clinically complete remission, partial remission or stable disease.

TPS, CA 15-3 and CEA were determined in metastatic breast cancer patients during treatment. After six months of follow-up the patients were divided into four groups according to the UICC criteria for treatment response. Forty-six patients with a more favorable prognosis (complete remission, partial remission or stable disease) were followed for an extended period. In 30 of the 46 patients at least one marker had increased at the end of the six-month period by at least 25% (TPS in 54%, CA 15-3 in 20%, CEA in 20%). All these 30 patients subsequently developed progression. The prognostic sensitivity was 83%, 30% and 30%, respectively, for TPS, CA 15-3 and CEA. The combination of TPS and CA 15-3 showed a sensitivity of 96%. The median lead time was about 8 months for TPS and CA 15-3, but less than 50% of the patients showed a lead time for CA 15-3 as compared to TPS. We conclude that TPS and CA 15-3 determinations are helpful for the prediction of progression during the follow-up of breast cancer patients.

Biomarkers, Tumor↗
PubMedDate not supplied

Prostate cancer probability after total PSA and percent free PSA determination.

UNLABELLED: The percent free PSA value is a promising diagnostic tool for prostate cancer. However, its actual role has not yet been established because of the widely diverging sensitivity and specificity values. This could depend at least in part on analytical difficulties, since the free PSA concentration is much lower than that of total PSA. The present investigation was designed to evaluate the diagnostic performance of the percent free PSA in the most favorable analytical conditions. MATERIALS AND METHODS: 81 patients affected by newly diagnosed, untreated primary prostate cancer (CaP) and 239 patients with untreated benign prostatic hyperplasia (BPH) were prospectively enrolled. Hybritech total and free PSA were measured by the same technician using the same reagent batch. RESULTS: The percent free PSA was not significantly associated with age, tumor stage, gland volume, Gleason score, and total PSA, nor was it significantly affected by concomitant prostatic complications either in CaP or BPH. Percent free PSA was more effective than total PSA in the differential diagnosis between CaP and BPH in every evaluated dose range of total PSA. Percent free PSA determination could have reduced the rate of unnecessary biopsies in cases with total PSA > or = 4 ng/mL and > or = 10 ng/mL (avoided biopsies 61% and 63%, respectively). The post-test probability of the disease, which represents the proportion of patients with a positive percent free PSA value who have the disease, was, however, relatively low in younger patients with total PSA within the normal range. CONCLUSIONS: The diagnostic performance of the percent free PSA value is enhanced when the methodological variability is reduced, particularly in men with low total PSA. Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 ng/mL. The percent free PSA value is effective in reducing the rate of unnecessary biopsies in men with total PSA higher than 4 or 10 ng/mL. However, due to its relatively low post-test probability, the percent free PSA value should be interpreted with caution in the decision-making related to individual patients and should be used in association with clinical and instrumental evaluation of the patient.

Aged↗
PubMedDate not supplied

Prognostic value of circulating KRAS2 gene mutations in colorectal cancer with distant metastases.

While tissue KRAS2 mutations have been extensively investigated, the role of circulating mutant KRAS2 gene in patients with colorectal carcinoma remains obscure. The aim of the present study was to explore the prognostic significance of circulating KRAS2 gene mutational status in subjects undergoing primary treatment for colorectal cancer. Codon 12 KRAS2 mutations were examined in DNA samples extracted from the serum of 86 patients with colorectal cancer and were compared with the KRAS2 status of their primary tumors. Tissue and serum KRAS2 status was compared with other clinicopathological variables (including CEA and CA 19-9 levels) and with cancer-related survival. KRAS2 mutations were found in tissue samples of 28 patients (33%); serum KRAS2 mutations were detected in 10 of them (36%). Serum KRAS2 status was significantly associated with Dukes' stage D (p=0.001) and with preoperative CA 19-9 levels (p=0.01). At multivariate analysis, cancer-related survival was associated with Dukes' stage (p<0.0001), CEA level (p=0.02), and mutant circulating KRAS2 (p=0.01). All 7 stage D patients with serum KRAS2 mutations died of the disease within 24 months of primary treatment; cancer-related survival was significantly better in 9 stage D patients without serum KRAS2 mutations, with 5 patients (56%) alive after 24 months and 1 patient (13%) alive after 44 months. Residual disease after surgery was evident in all 7 stage D patients with mutant circulating KRAS2, and in 5 out of 9 stage D patients without serum mutations. Serum KRAS2 status may impact substantially on the management of stage D colorectal carcinoma, since it appears to cor-relate with prognosis in this patient subgroup.

Adult↗
PubMedDate not supplied

Flexible modelling in survival analysis. Structuring biological complexity from the information provided by tumor markers.

The aim of the present article is to introduce and discuss the problem of optimal modelling of the prognostic information provided by putative prognostic variables, possibly measured on a quantitative scale. A number of methodological aspects will be treated, with particular reference to the role of spline functions and artificial neural networks, which will be discussed in the context of the analysis of survival data. The problem of the evaluation and the choice of the optimal statistical models will be examined, with particular attention to the critical aspects related to the definition of prognostic indexes on the basis of the results of the selected models. Clinical examples in breast cancer on the evaluation of the prognostic impact of several tumor markers are provided. This paper is addressed to all researchers who are interested in the evaluation of the prognostic role of tumor markers, therefore we will stress the necessity of integrating the methodologies of biological, clinical and statistical research in the assessment of prognosis.

Biomarkers, Tumor↗
PubMedDate not supplied

How tumor markers are used in the routine follow-up of breast and colorectal cancer. A survey of 29 Italian hospitals.

The impact of tumor markers on the outcome of several malignancies is still under debate. This relative uncertainty leads to a subjective approach to their use. Monitoring the use of tumor markers is a valuable tool to identify the need for educational policies. We conducted a survey to evaluate how tumor markers are routinely used in the follow-up of patients with breast, colorectal and ovarian carcinoma. The former two malignancies are considered in the present paper. We surveyed 35 Italian hospitals; 29 (83%, accounting for 26,622 hospital beds) filled in and returned the questionnaire. Overall, 467,361 tumor marker requests were scrutinized by the surveyed hospitals. We found a wide variability in the type and number of routinely used markers, the cutoff points chosen, and the clinical decisions taken on the basis of marker results. In addition, we observed a relative lack of communication between clinicians and clinical pathologists in around 50% of the surveyed hospitals. In these cases clinical information was not provided to the laboratory and methodological aspects were not communicated to clinicians. From the findings of the present study we conclude that the cooperation between clinicians and clinical pathologists must improve before guidelines for the use of tumor marker assays can be framed and the compliance with these guidelines can be checked. Request forms for tumor marker assays should therefore be designed to contain clinical information and the quality of filling in request forms with clinical data should be carefully monitored.

Biomarkers, Tumor↗
PubMedDate not supplied

Clinical relevance of vascular endothelial growth factor and thymidine phosphorylase in patients with node-positive breast cancer treated with either adjuvant chemotherapy or hormone therapy.

PURPOSE: To determine the role of the two angiogenic peptides, vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) (the latter also being a target enzyme for cytotoxicity of 5-fluorouracil and methotrexate), and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) probabilities in two cohorts of patients with node-positive breast cancer (NPBC) treated with either adjuvant chemotherapy (CMF [cyclophosphamide, methotrexate, 5-fluorouracil] schedule) or hormone therapy (tamoxifen). PATIENTS AND METHODS: We studied two groups of 137 and 164 patients with NPBC, median follow-up of 72 months for both, treated with adjuvant chemotherapy or hormone therapy, respectively. The cytosolic levels of VEGF and TP were determined in the primary tumor by original immunometric methods. The association between VEGF and TP and of these angiogenic peptides with other prognostic indicators were tested by using the Spearman correlation coefficient (for continuous variables) or the Kolmogorov-Smirnov test (for dichotomous variables). Results of the clinical outcome were analyzed by both univariate and multivariate (for RFS only) Cox regression models in which VEGF and TP were treated as continuous variables. RESULTS: In the CMF group, the concentrations of VEGF and TP ranged from 5.8 to 7798 pg/mg of protein (median, 87.5 pg/mg) and from 1.2 to 904 U/mg (median, 138.2 U/mg), respectively. There was no significant association between the two angiogenic peptides. VEGF was not associated with any other variable, whereas TP showed a positive association with age and an inverse association with the number of involved nodes. In the tamoxifen group, the concentrations of VEGF (5.9-2482; median, 79.3 pg/mg protein) and TP (6.1-1542; median, 146.5 U/mg) were similar to those of the CMF group, and the two angiogenic peptides were not correlated. VEGF was positively associated with age and was inversely associated with estrogen receptor and progesterone receptor, whereas TP was not associated with any other variable. Univariate analysis in the CMF group showed that VEGF and TP were significantly predictive of both RFS and OS. Likewise, the number of involved axillary nodes was significantly associated with both RFS and OS. Univariate analysis in the tamoxifen group showed that TP did not significantly influence either RFS or OS. On the contrary, VEGF levels were significantly predictive of both RFS and OS, as were the number of involved nodes, estrogen receptor concentrations, and progesterone receptor concentration. In the multivariate analysis on RFS in the CMF group, VEGF, TP, their first-order interaction term, and age were significant and independent predictive factors. In the tamoxifen group, only VEGF and the number of involved nodes were significant and independent predictive factors. DISCUSSION: The results of our study suggest that high levels of TP and low levels of VEGF characterize the patients with NPBC treated with adjuvant CMF who have the highest likelihood of favorable outcome. Low levels of VEGF and the presence of less than three involved axillary nodes characterize the patients with NPBC treated with adjuvant tamoxifen who have the highest likelihood of favorable outcome. This information may be useful to plan future studies to better select the patients with NPBC for conventional adjuvant treatments as well as to monitor the efficacy of novel therapeutic strategies of adjuvant therapy based on inhibition of angiogenesis.

Adult↗
PubMedDate not supplied

Tumor markers in breast cancer monitoring should be scheduled according to initial stage and follow-up time: a prospective study on 859 patients.

PURPOSE: The purpose of this study was to identify and standardize optimal decision criteria for maximizing the effectiveness of tumor markers in clinical use during the follow-up of patients operated on for breast cancer. MATERIALS AND METHODS: The study was prospectively performed on 859 patients enrolled in 10 institutions. A total of 13,337 determinations of CEA and 14,330 determinations of CA15.3 were available. The median number of samples per patient was 16 for CEA and 17 for CA15.3. The median follow-up was 7 years. Receiver-operating characteristic analysis was used to evaluate the ability of CEA and CA15.3 to discriminate relapses from patients who had no evidence of disease. The diagnostic performances of the two markers were evaluated using decision criteria based on both dichotomic cut-off points and dynamic variations among serial samples. RESULTS: We selected decision levels corresponding to preset levels of 90% and 99% specificity. Patients with CEA and/or CA15.3 levels above the cut-off values were considered positive only if a 1.5-fold increase occurred among the last sample and the mean of the first three samples. According to the different cut-offs used, specificity ranged from 94% to 99% and sensitivity from 48% to 63%. We calculated predictive values using the prevalence expected with reference to the stage of primary tumor and the length of follow-up. Positive predictive values ranged from 1.6% to 93.7%, and negative predictive values from 88.9% to 100%, according to the clinical scenarios and the decision criteria used. The choice of the decision criteria significantly affected positive predictive values within each patient subset. Differences related to time from surgery were still remarkable for every decision criteria (i.e., positive predictive values ranged from 36.6% to 2.8% in node-negative patients according to the year of observation, although the same cut-off point was used). DISCUSSION: The results of the present prospective study show that different decision criteria may provide different diagnostic performances for the same tumor marker and in the same patient. Therefore, we suggest that different decision criteria be settled and used according to the clinical goals.

Biomarkers, Tumor↗
PubMedDate not supplied

Validation of blood collection procedures for the determination of circulating vascular endothelial growth factor (VEGF) in different blood compartments.

AIMS OF THE STUDY: Studies on circulating VEGF have reported mixed results, possibly due to a lack of standardization of the pre-analytical phase. The aim of our investigation was to standardize the sampling procedure for the determination of VEGF in different blood fractions. BASIC PROCEDURES: We evaluated various clotting times for obtaining serum in 30 subjects, as well as different procedures for the preparation of plasma Edinburgh anticoagulant mixture (EDTA, PGE1, theophylline) and CTAD. VEGF was also assayed in lysed whole blood. In vitro platelet activation was monitored by measuring the levels of PF4. VEGF and PF4 were measured using commercially available enzyme-linked immunoassays. MAIN FINDINGS: Clotting time increased the release of VEGF, which reached a plateau between 2 and 4 hours. The percent increase of VEGF at 2 hours ranged from 118% to 4,515% (median 327%) compared to samples centrifuged within 10 min from withdrawal. VEGF was not different and PF4 was very low or undetectable in Edinburgh plasma and CTAD plasma, while it was significantly higher in sodium citrate plasma. VEGF in CTAD plasma was not correlated with platelet count or leukocytes. Serum VEGF did not correlate with the leukocyte number, but it correlated significantly with the platelet count. PRINCIPAL CONCLUSIONS: The procedures for sample collection described above are highly standardized and easy to perform in a routine setting. We therefore suggest systematic evaluation of VEGF in CTAD plasma, in serum (clotting for 2 hours at room temperature) and in whole blood, until prospective controlled clinical studies will have clarified in which blood compartment(s) VEGF provides clinically relevant information.

Biomarkers, Tumor↗
PubMedDate not supplied

Immunoenzymatic assay of erbB2 protein in cancer and non-malignant breast tissue. Relationships with clinical and biochemical parameters.

The erbB2-encoded protein p185 was determined in 130 breast cancer specimens and in 29 non-malignant breast tissues using a recently available ELISA method. The assay showed good characteristics of precision and accuracy. In the non-malignant tissue p185 concentrations were normally distributed and directly correlated with estrogen receptors (ER) and progesterone receptors (PR). In cancer tissue p185 showed higher concentrations than in non-malignant tissue. No relationships were found between p185 and the main clinical and pathological parameters, except that a direct association with nuclear grade was found. We have categorized the breast cancer samples according to p185 concentrations as p185-negative (concentrations lower than the higher non-malignant tissue) and p185-positive. Our data suggested a different behaviour of p185 in samples with low or high p185 concentrations. Indeed, in p185-negative samples the concentrations were directly correlated with both ER and PR. Conversely, p185-positive samples were directly associated with node status and pT, and inversely associated with ER and PR.

Adult↗