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Biomedical subjects

M T Allende

Publications and source records attributed to M T Allende.

At least 19 recordsLinked to original sources

Expression and prognostic value of EGFR in invasive breast cancer.

Epidermal growth factor receptor (EGFR) is a membrane receptor expressed in a variety of solid human cancers and directly related with poor prognosis. The objective of this work was to evaluate the EGFR content in breast carcinomas, its possible relationship with different clinical-pathological parameters, and its potential prognostic significance and predictive value. EGFR levels were examined by radioligand binding assays in 846 patients with invasive breast cancer. The median follow-up period was 50 months. There was a wide variability of EGFR levels among the studied tumors (0.01-403 fmol/mg protein). Statistical analysis showed that EGFR levels were significantly higher in younger patients (p=0.0001). EGFR were also notably higher in ER-negative or PgR-negative tumors than in ER-positive (p=0.0001) or PgR-positive tumors (p=0.001). In addition, the presence of high intratumoral EGFR levels (cut-off: 6 fmol/mg protein) was associated with both shorter relapse-free survival (p=0.04) and overall survival (p=0.01) in the group of patients as a whole, as well as with overall survival in the subgroup of patients without any type of systemic adjuvant treatment (p=0.02). However, EGFR levels did not achieve significance as independent prognostic factor in the multivariate analysis. There is a wide variability of intratumoral EGFR levels in breast carcinomas, and these protein levels correlated positively with a poor prognosis in the t univariate analysis. However, further studies are necessary in order to assess the possible clinical value of EGFR in combination with other essential components of the EGFR family network.

Adult↗

[Clinical significance of tumor content of epidermal growth factor receptor in breast cancer].

OBJECTIVE: To determine the content of epidermal growth factor receptor (EGFR) using a radioligand method in breast cancer and to analyze the relationship between the EGFR levels and the characteristics of patients and tumors. Prognostic significance was also analyzed. MATERIAL AND METHODS: EGFR was measured by a single point radioligand assay in 265 invasive breast carcinomas tissues. In addition, estrogen and progesterone receptors (ER and PR) were measured by enzymatic immunoassays. We analyze the relationship of EGFR levels with the different clinico-pathologic parameters. RESULTS: EGFR levels in breast carcinomas varied widely (0.1 to 403) with a median at 4 fmol/mg prot. The significantly higher concentrations of EGFR were detected in patients under 60 years old (p = 0.042), undifferentiated tumors (p = 0.04), and carcinomas with negative ER and PR (p < 0.019 y p < 0018, respectively). In addition, there was a negative correlation between EGFR and the ER and PR levels (p < 0.05). EGFR levels did not show any relationship with the patient's prognosis. CONCLUSIONS: In addition, intratumoral levels of EGFR in breast carcinomas vary widely and the highest concentrations are associated with the most aggresive characteristics of the tumor.

Adult↗

[Analysis of the cytosolic content of the pS2 protein in breast cancer].

OBJECTIVE: To analyze pS2 cytosolic levels in breast carcinomas and their correlation with different clinical characteristics of the patients and their tumours. MATERIAL AND METHODS: Cytosolic pS2 levels were measured by radioimmunometric assay in tumours from 168 breast cancer patients. RESULTS: The pS2 values ranged from 0 to 251 ng/mg protein (mean SD: 21.8 38.1; median: 7.9 ng/mg protein). These protein levels were significantly (p < 0.05) higher in premenopausal patients (27.6 45.2) than in postmenopausal patients (19.5 33.8). Intratumour pS2 levels were also significantly (p < 0.05) correlated with histologic grade of the tumours, and were higher in well diferentiated tumours (grade I: 28.8 42.8) than in moderately differentiated tumours (grade II: 19.7 35.6) and than in poorly differentiated tumours (grade III: 18.9 37.3). Similarly, significant differences in pS2 content were found between positive estrogen receptor (ER) tumours and ER-negative tumours (29.1 46.5 vs 11.3 15.9, respectively; p<0.0001), as well as between positive progesterone receptor (PR) tumours and PR-negative tumours (29.1 49.8 vs 15.3 21.5, respectively; p < 0.05). CONCLUSIONS: The results suggest that pS2 may be a useful prognostic marker in breast cancer, and may also be useful to identify patients who are likely to benefit from hormone therapy.

Adult↗

Hyaluronic acid as prognostic marker in resectable colorectal cancer.

BACKGROUND: Hyaluronic acid (HA), an extracellular high molecular mass polysaccharide, is thought to be involved in the growth and progression of malignant tumours. The objective of this work was to evaluate the cytosolic HA content in resectable colorectal cancer, its possible relationship with clinicopathological parameters of tumours and its prognostic significance. METHODS: Cytosolic HA levels were examined by radiometric assay in 120 patients with resectable colorectal cancer. The mean follow-up period was 33.4 months. RESULTS: Cytosolic HA levels of tumours ranged widely, from 30 to 29 412 ng per mg protein. Intratumour HA levels were significantly correlated with Dukes stage (P < 0.005), and were higher in patients with advanced tumours (mean(s.e.m.) 2695(446), 2858(293) and 5274(967) ng per mg protein for stages A, B and C respectively). In addition, Cox multivariate analysis demonstrated that tumour HA levels higher than 2000 ng per mg protein predicted shorter relapse-free survival and overall survival periods (both P < 0.05). CONCLUSION: There is a wide variability in cytosolic HA levels in colorectal carcinomas, which seems to be related to the biological heterogeneity of these tumours. In addition, high tumour cytosolic HA levels were associated with an unfavourable outcome in patients with resectable colorectal cancer. HA may provide additional information to that given by other biochemical markers currently used in colorectal cancer.

Adult↗

C-erbB-2 oncoprotein content in colorectal cancer and in surrounding mucosa: relationship with clinicopathologic parameters and prognostic significance.

BACKGROUND: c-erbB-2 is a transmembrane signaling molecule closely related in structure to the epidermal-growth-factor receptor (EGFR) but biologically distinct from it. c-erbB-2 has been implicated in cell transformation and tumor pathogenesis, but very little is known about its content and clinical significance in colorectal cancer. AIMS: To evaluate the c-erbB-2 content in colorectal cancer and its possible relationship with clinicopathologic parameters from tumors and prognostic significance. METHODS: Membranous and cytologic c-erbB-2 oncoprotein contents were examined by an immunoenzymatic assay in tumors and paired normal surrounding mucosa samples from 131 colorectal cancer patients. In addition, survival analysis were prospectively performed in a subgroup of 69 consecutive patients with resectable colorectal carcinomas, who underwent a mean follow-up period of 28 months. RESULTS: In the overall group of patients, c-erbB-2 levels were significantly higher in membranous than in cytosolic samples, in neoplastic tissues (5,830.4 +/- 1085.3 vs. 934.2 +/- 107.5 NHU/mg protein; p < 0.0001) and in surrounding normal mucosa samples (5,257.8 +/- 646.3 vs. 837.4 +/- 187.4 NHU/mg protein; p < 0.0001). Nevertheless, a significant positive relation was found between membranous and cytosolic oncoprotein levels in these two paired sets (p < 0.0001, for both). There were no significant differences in membranous or cytosolic c-erbB-2 protein levels between neoplastic tissues and surrounding mucosa samples in this overall group of patients. In addition, the results did not show significant correlations of these oncoprotein contents with clinicopathologic parameters from tumors such as location, stage, histologic grade, and DNA content or S-phase fraction. However, the results indicated that low membranous c-erbB-2 content (< 4,500 NHU/mg protein) in tumors predict shorter relapse-free survival and overall survival (p < 0.05, for both) in resectable colorectal cancer patients. CONCLUSIONS: There are a wide variability of both membranous and cytologic c-erbB-2 contents in colorectal carcinomas, which seems to correspond to the biological heterogeneity of these tumors. In addition, our results also demonstrate that high membranous c-erbB-2 levels are associated with lesions of favorable evolution in resectable colorectal cancer patients.

Colorectal Neoplasms↗

[Valoration of the epidermal growth factor receptor (EGFR) in benign breast disease and its relation with expression in malignant tumors classified by hormonal dependence].

The aim of this work is studying the behaviour of EGFR in benign breast pathologies and correlating it to its expression in CDI with hormonal dependency or independency using a radioligand technique. The EGFR expression was higher in FAD rather than in MFQ (mean +/- S.D.: 13.7 +/- 13.5; range: 1.0-55.3; median: 10.0 fmol/mg prot vs mean +/- S.D.: 4.0 +/- 3.5; range:1.0-11.4; median: 2.2 fmol/mg prot), with a result of a positive correlation in the first ones with RP (r = 0.4557) but not with RE. FAD present similar EGFR concentrations to those in CDI-hormonal independents (mean +/- S.D.: 10.7 +/- 12.6; range: 1.0-60.2; median: 6.75 fmol/mg prot), even though the way they are correlated with the content in RP leads us to the conclusion that they are both involved in the genesis and controled development of themselves. On the other hand, MFQ have got similar contents in EGFR to those of CDI hormono-dependents (mean +/- S.D.: 6.98 +/- 15.72; range: 1.0-118; median: 2.55 fmol/mg prot); this fact proves that the development of this pathology does not only depend on the growth factors but also on the hormonal environment which influences it.

Adolescent↗

Analytical and clinical evaluation of a procedure for measuring CA 15-3 in the IMx analyser.

CA 15-3 is the most widely used tumour marker in the follow-up of patients with breast cancer. Its postoperative blood level is closely related to the response to the treatment applied and to the evolution of the disease. In this study, we assessed both the clinical and analytical features of a new microparticle enzyme immunoassay for CA 15-3 quantification in the Abbott IMx system. In the precision study, the coefficients of variation within runs, between runs and between laboratories were 3.5, 5.1 and 6.5% or less, respectively. The analytical sensitivity of the assay was 0.11 U/ml. Linear regression analyses of the IMx CA 15-3 assay with the Centocor and CIS CA 15-3 RIAs gave correlation coefficients of 0.88 and 0.95, respectively. The upper limit of the reference range, obtained from serum of healthy women, was 27.3 U/ml, while the ROC curve analysis for patients with active breast cancer compared to patients with no evidence of the disease gave an optimum cutoff of 33 U/ml (sensitivity 0.76 and specificity 0.87). The overall agreement of the three methods was over 90%.

Breast Neoplasms↗

Zn-alpha 2-glycoprotein levels in breast cancer cytosols and correlation with clinical, histological and biochemical parameters.

Zn-alpha 2-glycoprotein (Zn-alpha 2-gp), a protein present at high levels in breast cyst fluid, has been measured in 104 breast tumour cytosols by using an immunoenzymatic assay. Concentrations of Zn-alpha 2-gp ranged from 0 to 23.5 micrograms/mg of total soluble protein, with an average value of 2.4 micrograms/mg. There was no significant correlation between Zn-alpha 2-gp and menopausal status, tumour size or lymph node involvement, or between this protein and biochemical parameters such as oestrogen receptor, cathepsin D or pS2 levels. However, there was a significant association between Zn-alpha 2-gp and histological grade of tumours, with higher Zn-alpha 2-gp levels in well-differentiated tumours (mean 4.6 micrograms/mg) than in moderately (1.8 micrograms/mg) or poorly (0.9 micrograms/mg) differentiated tumours. On the basis of these results, we propose that Zn-alpha 2-gp may be considered as a biochemical marker of differentiation in breast cancer.

Adult↗

Quantification and molecular analysis of cathepsin D in breast cyst fluids.

Cyst fluids from 55 premenopausal women with gross cystic breast disease were classified by K+/Na+ ratio: 19 with ratio over 1 (type I) and 36 with ratio less than 1 (type II). Immunoradiometric assay of cathepsin D in both types of cyst fluids revealed the presence of large amounts of this proteinase. The average concentration of cathepsin D in type I cyst fluids was 63.3 nmol/l, which was significantly higher than that corresponding to type II cyst fluids (35.1 nmol/l). Immunoprecipitation analysis of intracystic cathepsin D demonstrated that this protein was present as the 52 kD non-processed precursor form of the molecule. Since procathepsin D is a useful prognostic marker in breast carcinoma, we suggest that cyst fluid quantification of cathepsin D could aid to detect patients affecting of gross cystic disease with higher risk for developing breast cancer.

Adult↗