Biomedical subjects

M Gion

Publications and source records attributed to M Gion.

At least 37 records · Page 2Linked to original sources

PubMed1997

Detection of different estrogen receptor forms in breast cancer cytosol by enzyme immunoassay.

Estrogen receptors (ER) are routinely measured in tissue extracts from breast cancer using a radioligand binding assay (RBA) and an enzyme immunoassay (EIA). Although good correlation was found between the two methods, they are expected to measure, at least in part, different ER amounts in individual samples, because the RBA should detect unfilled ER only, whereas EIA should recognize both unfilled receptors and those filled by endogenous estrogens. The purpose of the present investigation was to evaluate if ER-EIA mainly detects ER filled by endogenous estrogens when using an estrogen-free buffer to dilute cytosol samples. Indeed, the commercially available EIA assay kit (ER-EIA; Abbott) is equipped with a sample dilution buffer containing a high concentration of 17beta-estradiol which should allow for the saturation of all the ERs. ER was measured in 57 cytosol samples from primary breast cancer with RBA and ER-EIA. In the latter case, samples were diluted using both the estradiol-rich dilution buffer of the kit and an estrogen-free low salt phosphate buffer. RBA and ER-EIA showed tightly correlated results. However, ER-EIA detected higher ER levels than RBA in the majority of cases. Results obtained by low salt ER-EIA were also correlated to both RBA and ER-EIA, showing, however, lower ER concentrations. ER levels measured by ER-EIA were not significantly different from the sum of ER concentrations found by RBA and low salt ER-EIA. These findings suggest that ER-EIA detects ER only in the conformational status that is achieved after saturation by estrogens. These findings were confirmed by sedimentation shift experiments, which showed that the monoclonal antibody D547 used in the kit binds ER in the occupied form only. This leads to the conclusion that ER-EIA detects functioning (in terms of binding with estradiol) ERs. From the present investigation, we suggest that it is possible and probably worthwhile to optimize the EIA method by using different buffers to measure: (a) the total number of ERs capable of binding estradiol; (b) the ER filled by endogenous estrogens; and (c) by difference, the unfilled ER concentrations.

Antibodies, Monoclonal↗

PubMed1997

Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma.

BACKGROUND: The clinical outcome is generally positive for patients with node-negative breast carcinoma (i.e., those who do not have detectable metastases in the lymph nodes) who have been treated with surgery or surgery plus radiation therapy. In about 30% of the patients, however, the disease recurs, and they are at risk of death. Determination of valid new prognostic indicators would improve the ability to identify patients at high risk of recurrence. Breast cancer can entail substantial development of new blood vessels within the tumor tissue, and it is known that the growth and metastasis of solid tumors are dependent on such angiogenesis. The conversion of tumor cells to an angiogenic phenotype may be preceded by a change in the balance of angiogenic growth factors and angiogenesis inhibitors. PURPOSE: This study was conducted to determine if the levels of vascular endothelial growth factor (VEGF) protein, a potent endothelial growth factor and mediator of vascular permeability and angiogenesis, measured in the primary tumors of women with node-negative breast cancer are associated with known prognostic factors and patient survival. METHODS: By use of a selective enzymatic immunoassay, levels of VEGF protein were measured in cytosolic extracts of primary tumor tissue surgically obtained from 260 women with node-negative breast carcinoma who had been treated with surgery with or without radiation therapy but not with adjuvant therapy and who had been followed for a median time of 66 months. The relationships between VEGF concentrations and other prognostic dichotomous variables or clinical outcome were tested by the use of the Kolmogorov-Smirnov test and univariate and multivariate Cox analyses, respectively. The relationship between VEGF and hormone receptors (i.e., those for estrogen and progesterone) was examined by the use of Spearman's correlation analyses. All P values resulted from the use of two-sided statistical tests. RESULTS: Tumors from 247 (95%) of the 260 patients had detectable VEGF, ranging in concentration from 5.0 to 6523 pg/mg protein (median, 126.25 pg/mg protein). No statistically significant associations were found between VEGF and the other prognostic factors (e.g., age, menopausal status, histologic tumor type, tumor size, and hormone receptors) examined. Levels of VEGF were found to be prognostic for both relapse-free and overall survival in univariate and multivariate analyses (likelihood ratio tests; all four P values < .001). In the multivariate analysis, the first-order interaction term of VEGF and estrogen receptor was also prognostic for overall survival (likelihood ratio test; P = .05). CONCLUSIONS: The results show that cytosolic levels of VEGF in tumor tissue samples are indicative of prognosis for patients with node-negative breast carcinoma.

Adult↗

PubMed1997

Co-determination of the angiogenic factors thymidine phosphorylase and vascular endothelial growth factor in node-negative breast cancer: prognostic implications.

Experimental and clinical studies have shown that human breast cancer is an angiogenesis-dependent neoplasm. In fact, several authors have demonstrated that the determination in primary tumors of the degree of vascularization (microvessel counts) as well as of some angiogenic peptides is of prognostic value. However, which are the most important mediators of angiogenesis and their relationship with other relevant biological markers needs further investigation. In the series of 260 women with node-negative breast cancer (NNBC) on which we previously assessed vascular endothelial growth factor (VEGF), we have now also determined thymidine phosphorylase (TP) protein as well as p53 protein and Cathepsin-D cytosolic levels using immunometric methods. The median concentrations of TP, p53 and Cathepsin-D were 105.4U/mg (range 1.2-843.1), 0.22 ng/mg (range 0.0-41.65) and 33.80nmol/mg (range 4.20-216.0), respectively. We found that TP concentrations were associated with Cathepsin-D and p53, but not with VEGF. VEGF (p<0.0001) and p53 (p = 0.03 and p = 0.012, respectively) were found to be statistically significant prognostic variables for both relapse-free survival (RFS) and overall survival in univariate analysis. Conversely, TP and Cathepsin-D levels did not correlate with prognosis. In multivariate analysis for RFS, VEGF levels (p<0.0001), TP levels (p = 0.050) and their first-order interaction terms (p = 0.027) were statistically significant prognostic indicators. Cathepsin-D and p53 protein levels did not retain significance in the model inclusive of all the above variables. The predictive capability of the complete model was satisfactory (Harrell c statistic = 0.72). Moreover, these results suggest a possible potentiation of the capability of predicting the likelihood of recurrence by the co-determination of TP and VEGF. The probability of recurrence was particularly high in the patients with primary tumors characterized by elevated levels of both angiogenic factors. This is the first study showing in vivo that two different angiogenic peptides concur in the progression of human breast cancer. The biology and possible therapeutic implications of this observation are discussed.

Journal Article↗

PubMed1997

[Expression of estrogen receptors in breast cancer detected by various methods: lack of correlation].

Three methods are currently available for defining the estrogen receptor (ER) status in breast carcinomas. These include biochemical ligand binding assay (LBA), immunohistochemical (IC) and mRNA in situ hybridization (ISH) semiquantitative analysis. There is still a debate as to which method should be considered the "gold standard" to define ER status. To address this topic we evaluated the above three methods in a series of 43 breast neoplasms. The results of IC (on fixed sections with ER1D5 immunostaining) and LBA assay showed moderate correlation (p = 0.004), as there were 8 (18.6%) discrepant results. ISH was extremely sensitive, with 92% of positive results. ISH results did not correlate with either IC or LBA. In view of the relative lack of reciprocal correlation among the three methods, it is difficult to define which is the most accurate system to be used to localize ER in breast carcinomas. The easiest and least expensive method probably should be used. The immunohistochemical approach has the advantage of being easily applicable to routinely fixed material, to cytological specimen and is very useful in small lesions identified with mammography only.

Antibodies, Monoclonal↗

PubMed1996

Determination of ErbB2 protein in breast cancer tissues by different methods. Relationships with other biological parameters.

Four different methods to measure in parallel the erbB2 protein expression (p185neu) were evaluated in order to: a) compare two enzyme immunoassays with the immunohistochemical assays (IHC) and western blotting (WB) and b) extrapolate eventual relationships between erbB2 and biological parameters. Tissue samples from 248 patients with primary breast cancer were consecutively assayed. We used two different cut-off levels for WB, ELISA, and EIA, defined as follows: 1) the highest level of expression of non malignant tissue was chosen as the discriminant threshold between 'low' and 'elevated' samples: 2) the elevated group was further subdivided into two subgroups: 'intermediate' and 'high', according to their median value. According to the first cut-off, the results were considered 'elevated' in about 52% of cases with the three biochemical methods, while using the second cut-off the percentage lowered to about 26%. Considering this cut-off, the concordance rates between the paired biochemical methods ranged between: 78.4% (WB vs EIA), 93% (ELISA vs EIA), and 82.6% (ELISA vs WB). The comparison between biochemical and immunohistochemical methods gave these concordance rates: 82% (WB vs IHC), 90.5% (ELISA vs IHC), and 85.5% (EIA vs. IHC). According to the first cut off level, 27.5% of tumor samples showed IHC detectable p185 levels, in agreement with other immunohistochemical studies. The relationship between high erbB2 and estrogen and progesterone receptors showed an inverse association. No relationship was found between erbB2 and axillary lymph node positivity or tumor size. In short, the results of the four methods seem generally well correlated; nevertheless, it appears that different methodological approaches of measuring p185neu are not completely equivalent, and there is a need for an authoritative standardization and quality control for clinical applications.

Blotting, Western↗

PubMed1996

c-erbB-2/neu protein expression, DNA ploidy and S phase in breast cancer.

DNA content and c-erbB2/neu protein (p185) expression were evaluated by flow-cytometry and ELISA, respectively, in 166 specimens of primary breast cancer. A non-diploid DNA content was found in 88 tumours (53%), with the DNA index ranging from 0.7-2.7. S phase fraction (SPF) evaluation, performed in 130 cases, showed significantly higher values in aneuploid than in diploid tumours (median values, 17.3% and 5.8%, respectively). Thirty-six tumours (21.6%) showed p185 overexpression, while 45 (27.1%) and 85 (51.3%) showed intermediate and low expression, respectively. A good correlation (P = 0.0023) was found between DNA content and p185 positivity. Tumours with high p185 values were mainly aneuploid, while tumours with intermediate or low expression had variable degrees of DNA content. Furthermore, p185 concentration was significantly higher in aneuploid than in diploid tumours (P = 0.009). The highest rate of p185 (+) cases and the highest p185 concentrations occurred in triploid (1.3 < D.I. < or = 1.7), compared to the other tumours. SPF values and p185 positivity rates were not significantly correlated in diploid and in aneuploid tumours.

Adult↗

PubMed1996

Standardization of assay for cytokeratin-related tumor marker CYFRA21.1 in urine samples.

The determination of tumor markers in urine samples has been proposed as an effective diagnostic tool in bladder cancer. The aim of the present investigation was to validate in urine samples the assay of the CYFRA21.1 cytokeratin-related marker, the serum concentrations of which showed promising diagnostic utility in patients with bladder cancer. First-voided urine samples were collected from patients with different malignancies. CYFRA21.1 was assayed with a commercially available enzyme immunoassay (Boehringer Mannheim). Different centrifugation patterns, the use of different buffers and nonionic detergents, and pH variations were evaluated. We demonstrated that: (a) cells and cell debris contain a large amount of CYFRA21.1 and must be eliminated by centrifugation; (b) storage at -20 degrees C causes amorphous precipitate, which may aspecifically bind CYFRA21.1; (c) the latter behavior may be prevented by diluting fresh urine samples with phosphate buffer with nonionic detergent added; (d) pH variations within the range 4.9-8.2 do not significantly affect CYFRA21.1 assay results. Provided that samples are diluted with buffer containing nonionic detergent, the CYFRA21.1 assay showed good precision and accuracy characteristic in urine samples. We therefore propose a standard protocol for the collection of urine samples for CYFRA21.1 assay. In a preliminary clinical evaluation, CYFRA21.1 concentrations in 16 patients with primary bladder cancer were higher than in healthy subjects. In the urine collected in the follow-up of patients treated for bladder cancer, CYFRA21.1 tended to be higher in relapsed patients than in those without evidence of disease. These preliminary data induced us to extend the clinical trial to establish the actual role of this assay in routine use.

Antigens, Neoplasm↗

PubMed1995

Relationship between cathepsin D and other pathological and biological parameters in 1752 patients with primary breast cancer.

The relationship between cathepsin D and other pathological or biological prognostic parameters has not yet been defined through systematic studies in breast cancer. The aim of the present investigation was to define the relationship between cathepsin D and nodal status, tumour size, steroid receptors and tumour grade in a wide patient series. Cytosol cathepsin D was assayed with an immunoradiometric assay in tumour samples from 1752 patients. A statistically significant, but not biologically meaningful association was found between cathepsin D and both tumour size and grade. Cathepsin D was significantly higher in node-positive than in node-negative tumours. However, cathepsin D is not of great use in order to predict the risk of axillary metastases in individual patients, due to overlapping of cathepsin D values between node-positive and node-negative cases. A significant, direct association was found between cathepsin D and both oestrogen receptor and progesterone receptor cytosol levels. Nevertheless, preliminary data indicate that cathepsin D and steroid receptors provide independent prognostic information.

Adult↗

PubMed1995

Tumor markers in breast cancer follow-up: a potentially useful parameter still awaiting definitive assessment. Forza Operativa Nazionale sul Carcinoma Mammario (FONCaM).

BACKGROUND: Although tumor markers are frequently used in the follow-up of patients with breast cancer, two points are still being debated: 1) their cost/effectiveness has been neither demonstrated nor disproved; 2) the reliability of the currently used dichotomous division into a positive/negative cut-off should be definitely validated. Dynamic criteria of interpretation based on serial serum samples would probably be more effective for early detection of relapse. PATIENTS AND METHODS: The aim of the present study was to compare the dichotomous cut-off based decision criteria to a dynamic serial sample based assessment of tumor markers. Since 1989, 794 patients have been followed in 11 institutions. CEA and CA15.3 were measured once a month for three months before every clinical examination. The present paper concerns the evaluation variability in 405 patients without evidence of disease in the first three institutions joining the study. RESULTS: In patients without evidence of disease, the coefficient of variation of all samples for every patient showed a median value of 19 for CEA and 21 for CA15.3. Variability was negatively associated with the antigen level and was most likely due to the analytical component. This was also confirmed by the significant difference in variability among the three institutions evaluated. The median value of the critical difference was 53% for CEA and 57% for CA15.3. CONCLUSIONS: 1) Individually tailored dynamic decision criteria are applicable in about 50% of the cases. 2) The problem of improving the precision of tumor marker assays in the low dose range must be urgently addressed to the manufacturers of tumor markers by the scientific community in order to apply individually tailored decision criteria for patients in whom the serum level of biological markers is low.

Biomarkers, Tumor↗

PubMed1995

Appropriateness of the use of clinical and radiologic examinations and laboratory tests in the follow-up of surgically-treated breast cancer patients. Results of the Working Group on the Clinical Aspects of Follow-up.

BACKGROUND: The aim of this working group was to assess the appropriateness of use of radiologic examinations, laboratory tests and periodic check-ups for surgically-treated, disease-free breast cancer patients. MATERIALS AND METHODS: A total of 252 clinical scenarios (36 for each of the 8 exams considered: clinical examination, mammography, chest roentgenography, hematochemical tests, markers, bone scan, liver echography/abdominal CT scan), each representing a specific surgically treated and disease-free breast cancer patient, were rated by the members of the panel. A 3 point scale was utilized as to whether the test in question was judged inappropriate (1), questionable (2), or appropriate (3) (in the latter case the panel member was also asked for the advised frequency of the exam expressed in months). RESULTS: After two assessment sessions, consensus among members of the panel was reached on 216 of the 252 scenarios; disagreement remained on only 36 clinical scenarios. CONCLUSIONS: The panel agreed that only clinical examinations and mammographies should be recommended for routine clinical follow-up of surgically-treated breast cancer patients. Given the current available therapeutic options, these would assure adequate medical care and psychological aid.

Aged↗

PubMed1995

Prostate-specific antigen as a unique routine test in monitoring therapy for inoperable prostate cancer: comparison with radionuclide bone scan and prostatic acid phosphatase.

The aim of the present investigation was the evaluation of cost-effectiveness of variables used in monitoring patients with inoperable prostate cancer. Prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and radionuclide bone scan were considered. The tumor marker positivity was assessed according to dynamic criteria (> 50% increase between consecutive samples). 108 patients entered the study; 72 patients treated with a luteinizing hormone-releasing hormone analogue were followed up for periods ranging from 12 to 64 months. PSA and PAP levels were measured using immunometric assays. Both cutoff-based and dynamic, serial sample-based decision criteria were employed. With respect to a positive bone scan, PSA showed negative predictive values of 82 and 77%, respectively, using 4 and 10 ng/ml as cutoff points. Progression of the disease to the bone occurred in 20 patients: in 17 PSA was the first indicator of progression, in the other 3 PAP anticipated PSA for a very short time (3-4 months), which was not of relevance to clinical decisions. PAP is less specific and sensitive than PSA; PAP may eventually provide information on disease status in a limited percentage of patients with advanced prostate cancer treated with androgen ablation, being differently regulated with respect to PSA. No increasing PSA profile was detected in patients who responded to the therapy. From the results of the present investigation, we draw the following conclusions: (1) PSA can be used reliably as a unique tool in the follow-up of patients for the early detection of progressive disease, and (2) dynamic criteria of evaluation of serial PSA determinations probably provide more effective and earlier clinical information.

Acid Phosphatase↗

PubMed1995

How alternative are immunoassay systems employing non-radioisotopic labels? A comparative appraisal of their main analytical characteristics.

The immunoassay is one of the most sensitive and reliable analytical techniques available in the clinical laboratory. The original label for immunoassays was radioisotopes, and these methods, radioimmunoassay (RIA) and immunoradiometric assay (IRMA) are still the reference methods, because of invulnerability of the radioactive emission with respect to environmental interference. Labels other than radioisotopes have been tested for use in immunoassay to improve the sensitivity and reliability and to avoid some of the disadvantages of radioisotopic techniques. New labels have continued to be developed (Horseradish peroxidase-HPR-, pyrophosphatase, luciferases, pyrodopirazines, europium cryptates, porphirins, phosphors) and new label detection methods have been set up (e.g. chemiluminescence assay, thermometric assay, NADP+ and FADP- based coupled assay). New immunoassay strategies such as simultaneous multianalyte automated test have been developed and the reliability of the assays has in some cases caused division among researchers about the choice between the radioisotopic immunoassay or the non-radioisotopic immunoassay, as considerable effort and investment had been devoted to the search for more sensitive and practicable tests than the classic RIA-IRMA methods. The evolution of immunoassays (Monoclonal Antibodies, non-radioactive tracers, automation) has produced systems which allow a large number of laboratories to determine a great number of analytes with very good practicability. The availability of fully automated systems has generated the opinion that analytical performance of immunoassays can be considered similar to that of many traditional parameters of clinical chemistry. This conclusion seems however too optimistic, in fact data collected from interlaboratory studies demonstrate that problems concerning the analytical reliability of the measurements still remain not completely solved. In the authors' opinion, this opposition between immunological assay based on isotopic or non-isotopic labels is misleading, because each assay (whether it uses isotopic, enzymatic, fluorimetric or luminescent labels) has its own analytical characteristics and performance. For this reason the term "alternative", used to indicate all non-isotopic assays as a unique class of tests, should be abandoned. From a theoretical point of view the choice should not be between isotopic and non isotopic techniques. For each analyte to be tested, it is advisable to use the immunological assay that suits the requirements of the laboratory, irrespective of type of label. From a practical point of view, the choice should be based on the analytical performance and on the characteristics of each assay, on its cost and the type of instrumentation available in the laboratory, and on the experience and the knowledge of the laboratory personnel.

Costs and Cost Analysis↗

PubMed1994

Serum CA549 in primary breast cancer: comparison with CA15.3 and MCA.

We carried out a comparison of three commonly used mucin markers, CA549, CA15.3 and MCA. Serum samples from 184 healthy women and 237 patients with primary breast cancer were evaluated. The markers were measured using commercially available immunometric assays. Like CA15.3 and MCA, CA549 was significantly associated with tumour size and lymph node status, being an effective indicator of tumour bulk. CA549 was significantly correlated with both CA15.3 and MCA. Positive/negative concordance rate was very good (93.7%) between CA549 and MCA. Conversely, CA15.3 was positive and CA549 negative in 20.4% of cases. Axillary status was not significantly different in the latter group of patients and in cases in which CA15.3 and CA549 showed concordant results. From the present findings we draw the following major conclusions: 1. CA549 and MCA are highly correlated and their association should not provide additional information; however, they should not be considered interchangeable since they may behave differently in individual cases. 2. CA549 and CA15.3, although well correlated, are discordant in a significant number of cases. Longitudinal studies are needed to verify the usefulness of the association between the two markers. 3. The three evaluated mucin markers are not interchangeable in individual patients; if a patient is monitored with a marker, she should be followed up with the same marker.

Adult↗

PubMed1994

Tissue polypeptide antigen and tissue polypeptide specific antigen in primary breast cancer. Evaluation in serum and tumour tissue.

Tissue polypeptide antigen, measured by both a polyclonal antibody (TPA IRMA Prolifigen) and a monoclonal antibody prototype kit (TPA-M IRMA Prolifigen), and the tissue polypeptide specific antigen were evaluated. The markers were measured in 266 serum samples and in 291 tumour cytosols from patients with primary breast cancer. The three markers were available in matched pairs of both serum and cytosol from the same patient in 144 cases. Diagnostic sensitivity of serum levels of the three markers was not significantly different when using cut-off values calculated on the basis of healthy subjects. In the cytosol, tissue polypeptide antigen (TPA IRMA), tissue polypeptide antigen (TPA-M IRMA) and tissue polypeptide specific antigen were significantly correlated with steroid receptor status, while their serum levels were not. Cytosol and serum levels of the three markers were not significantly associated. All three were significantly correlated both in serum and in cytosol. The association was closer between tissue polypeptide antigen (TPA IRMA) and tissue polypeptide antigen (TPA-M IRMA) than between each of these two markers and tissue polypeptide specific antigen. From these findings we draw the following conclusions: 1. Tissue polypeptide specific antigen (TPA IRMA) and tissue polypeptide antigen (TPA-M IRMA) probably provide superimposable information both in serum and in cytosol; 2. Tissue polypeptide specific antigen and tissue polypeptide antigen (TPA IRMA) or tissue polypeptide antigen (TPA-M IRMA), although closely associated, probably measure in part different cytokeratins. Therefore, they should not be considered interchangeable in individual patients; 3. The determination of the markers in serum and in cytosol provides different information concerning the tumour phenotype.

Antibodies, Monoclonal↗

PubMed1993

Epidermal growth factor receptor in breast cancer. Comparison with non malignant breast tissue.

Epidermal growth factor receptors were measured using a radioligand binding assay in membrane preparations from 67 cancer and 25 non-malignant tissues. The binding characteristics of EGFr were similar in tumour and normal breast membranes. The concentrations were significantly higher in non-malignant tissue than in cancer. EGFr concentrations were directly correlated with steroid receptors in non-malignant tissue, whereas in cancer an inverse correlation between EGFr and steroid receptors was found.

Aged↗

PubMed1993

PS2 in breast cancer--alternative or complementary tool to steroid receptor status? Evaluation of 446 cases.

The oestrogen induced pS2 protein was measured in the cytosol of 446 breast cancer samples by an immunoradiometric assay. The relationships between pS2 and several clinical and biological parameters were evaluated. pS2 was not correlated to age, pT and nodal status, while it was higher in pre- than in peri- and post-menopausal women. A statistically significant positive association was found between pS2 and ER, PgR and cathepsin D. However, the frequency of pS2 negative values in ER+ (25.6%), PgR+ (21.7%) and cathepsin D-(19.0%) cases suggests that pS2 provides information independent of the above parameters in a fairly high percentage of patients. The prognostic role of pS2 was evaluated in 267 cases (follow up time 24-102 months). pS2+ showed longer RFS (P = 0.016) and OS (P = 0.004) than pS2-. pS2+ cases were significantly associated with a better prognosis in N+ but not in N- cases. Multivariate analysis showed that pS2 is an independent prognostic factor being the second most effective indicator for OS after nodal status and the third for RFS after nodal status and cathepsin D. From the present findings, we conclude that pS2 probably provides additional biological information to steroid receptor status and cathepsin D in patients with primary breast cancer.

Adult↗

PubMed1993

Variability of tumor markers in the follow-up of patients radically resected for breast cancer.

The biological and analytical components of variability of tumor markers should be distinguished from the variations due to tumor progression. The aim of the present study was to evaluate tumor marker variability in the follow-up of patients resected for breast cancer. So far, we have carried out 2,085 CEA and 2,550 CA 15-3 determinations in 435 patients. The total variability of both CEA and CA 15-3 was widely scattered among different subjects (CEA coefficient of variation 0-105%; CA 15-3 coefficient of variation 0-89.2%). The biological variability of CA 15-3, which was calculated in a limited number of cases, was scattered between 0 and 23% and was higher than the intra-assay variability. From these findings we conclude that when evaluating serial marker assays the intra-individual variability should be assayed initially to obtain a reference value of individual variability in relapse-free conditions.

Analysis of Variance↗

PubMed1992

Tissue polypeptide antigen in breast cancer cytosol: a new effective prognostic indicator.

Since 1982 we have been evaluating oestrogen and progesterone receptors (PgR), cathepsin D and the cytosolic levels of the tumour marker, tissue polypeptide antigen (TPA), in 257 patients radically resected for breast cancer (follow-up 24-81 months). TPA was measured by an immunoradiometric assay previously validated for cytosol. No significant associations were found between cytosolic TPA and age, tumour size, lymph-node status, receptor status and cathepsin D. TPA+ cases showed a significantly longer disease-free survival (DFS) and overall survival (OS) than TPA-patients (log-rank P < 0.0001). The prognostic value of cytosolic TPA was also demonstrated after stratification by nodal status, PgR and cathepsin D. The prognostic value of TPA was independent of the other prognostic indicators, being the most powerful among the evaluated indices (Cox multivariate analysis: chi 2 15.5 for DFS, 11.4 for OS). We conclude that cytosolic TPA is a powerful additional prognostic factor in primary breast cancer. Its prognostic role should therefore be extensively evaluated.

Antigens, Neoplasm↗