Preoperative coagulation screening tests in pediatric patients: Clinical relevance and hemorrhagic outcomes of abnormal results.

PURPOSE: Coagulation screening tests in children are still frequently performed in many countries to evaluate bleeding risk. The aim of this study was to assess the management of unexpected prolongations of the activated partial thromboplastin time (APTT) and prothrombine time (PT) in children prior to elective surgery, and the perioperative hemorrhagic outcomes. METHODS: Children with prolonged APTT and/or PT who attended a preoperative anesthesia consultation from January 2013 to December 2018 were included. Patients were grouped according to whether they were referred to a Hematologist or were scheduled to undergo surgery without further investigation. The primary endpoint was to compare perioperative bleeding complications. RESULTS: 1835 children were screened for eligibility. 102 presented abnormal results (5.6%). Of them, 45% were referred to a Hematologist. Significant bleeding disorders were associated with a positive bleeding history, odds ratio of 51 (95% CI 4.8-538.5, P=.0011). No difference in perioperative hemorrhagic outcomes were found between the groups. An additional cost of 181 euros per patient and a preoperative median delay of 43 days was observed in patients referred to Hematology. CONCLUSIONS: Our results suggest that hematology referral has limited value in asymptomatic children with a prolonged APTT and/or PT. Hemorrhagic complications were similar among patients referred and not referred to Hematology. A positive personal or family bleeding history can help identify patients with a higher bleeding risk, thus it should guide the need for coagulation testing and hematology referral. Further efforts should be made to standardize preoperative bleeding assessments tools in children.

Dedicated breast PET value to evaluate BI-RADS 4 breast lesions.

PURPOSE: To evaluate the diagnostic value of dedicated breast PET (dbPET) parallel imaging in mammographically or sonographically detected BI-RADS 4 (Breast Imaging Reporting And Data Systems) lesions. MATERIALS AND METHODS: After institutional review board and patient approvals, 50 consecutive women with 60 BI-RADS 4 breast lesions were prospectively included in the study. All patients underwent Magnetic Resonance Imaging (MRI) and dbPET before biopsy and fusion of both MRI and dbPET images was performed to better locate corresponding lesions. Final findings were compared with histological results. Sensitivity and specificity for dbPET were determined along with their respective 95%-confidence intervals. RESULTS: Histopathology examination revealed 18 malignant lesions (7 in situ and 11 invasive carcinomas) and 42 benign entities. The dedicated breast PET reported no evidence of malignancy in 41 patients, 9 of them with histological diagnosis of neoplasm. Besides, dbPET showed increased metabolically activity in 10 benign lesions and in 9 breast cancers. Two invasive carcinomas were located less than 1 cm from the pectoral muscle, which can explain that they were missed by dbPET because they were outside the field of view (FOV). There were other 6 false negative results, which corresponded to a 0.1 cm invasive lobular carcinoma and 5 in situ carcinomas. Sensitivity and specificity of dbPET were 50% and 76%, respectively. CONCLUSIONS: Our analysis does not allow the recommendation of dbPET for diagnosis of malignancy in BI-RADS 4 mammographic or US abnormalities, mainly due to its high false-negative rate for the detection of in situ carcinomas (85.7%). However, considering the lesions greater than 0.1 cm and included in the FOV, dbPET depicted all invasive carcinomas.

HIN-1: a New Epigenetic Biomarker Crucial for Therapy Selection in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common brain tumor in adults. The role of high in normal-1 (HIN-1) as a potential biomarker in combating this disease is being described for the first time in this study. A combination of O6-methylguanine DNA methyltransferase (MGMT) and HIN-1 methylation could be a possible biomarker in therapy choice. Interestingly, survival data shows a similar trend for the methylation of MGMT and for unmethylation of HIN-1 and vice versa. Eighty-eight paraffin-embedded brain tumors were analyzed to screen methylation rates of different genes and evaluate the association between genes methylation and clinicopathologic variables. Our study is the first of its kind to indicate that MGMT and HIN-1 methylation status are inverted (97.7% of methylated ones) and could be new markers in the study of GBM prognosis, especially in the therapy selection.

Simulated FDG-PET studies for the assessment of SUV quantification methods.

AIM: To study in detail the accuracy and repeatability of three commonly used methods for SUV estimation in solitary pulmonary nodules. MATERIAL AND METHODS: We have designed a realistic framework based on simulated FDG-PET acquisitions from an anthropomorphic activity model that included solitary pulmonary nodules (different sizes) of well-known SUV. This framework enables us to compare the SUV values obtained from the reconstructed PET images with the real SUV values. Three commonly used methods (SUVmax, SUVmean and SUV50) were used to estimate the tumor activity. RESULTS: Our results showed the tumor activity was overestimated using SUVmax and clearly subestimated using SUVmean. Instead, the quantification of SUV50 showed great agreement with the simulated tumor activity and only slight subestimation was found for very small lesions. On the other hand, SUVmean showed better performance than SUV50 in terms of repeatability, providing variabilities below 5% for all tumor sizes and for injected doses as low as 111 MBq. CONCLUSIONS: Our findings showed that SUV50 provided better performance for estimating accurately tumor SUV values in pulmonary nodules, but SUVmean showed better results in terms of repeatability.

The performance of a hybrid analytical-Monte Carlo system response matrix in pinhole SPECT reconstruction.

It is well-known that in pinhole SPECT (single-photon-emission computed tomography), iterative reconstruction methods including accurate estimations of the system response matrix can lead to submillimeter spatial resolution. There are two different methods for obtaining the system response matrix: those that model the system analytically using an approach including an experimental characterization of the detector response, and those that make use of Monte Carlo simulations. Methods based on analytical approaches are faster and handle the statistical noise better than those based on Monte Carlo simulations, but they require tedious experimental measurements of the detector response. One suggested approach for avoiding an experimental characterization, circumventing the problem of statistical noise introduced by Monte Carlo simulations, is to perform an analytical computation of the system response matrix combined with a Monte Carlo characterization of the detector response. Our findings showed that this approach can achieve high spatial resolution similar to that obtained when the system response matrix computation includes an experimental characterization. Furthermore, we have shown that using simulated detector responses has the advantage of yielding a precise estimate of the shift between the point of entry of the photon beam into the detector and the point of interaction inside the detector. Considering this, it was possible to slightly improve the spatial resolution in the edge of the field of view.

Preliminary experience with small animal SPECT imaging on clinical gamma cameras.

The traditional lack of techniques suitable for in vivo imaging has induced a great interest in molecular imaging for preclinical research. Nevertheless, its use spreads slowly due to the difficulties in justifying the high cost of the current dedicated preclinical scanners. An alternative for lowering the costs is to repurpose old clinical gamma cameras to be used for preclinical imaging. In this paper we assess the performance of a portable device, that is, working coupled to a single-head clinical gamma camera, and we present our preliminary experience in several small animal applications. Our findings, based on phantom experiments and animal studies, provided an image quality, in terms of contrast-noise trade-off, comparable to dedicated preclinical pinhole-based scanners. We feel that our portable device offers an opportunity for recycling the widespread availability of clinical gamma cameras in nuclear medicine departments to be used in small animal SPECT imaging and we hope that it can contribute to spreading the use of preclinical imaging within institutions on tight budgets.

Only in patients with hormone-dependent breast infiltrating ductal carcinomas, CA15.3 serum levels are inversely correlated with the immunohistochemical expression of Bcl2.

OBJECTIVE: To study possible association between serum CA15.3 levels and immunohistochemical expression of Bcl2 in women affected by infiltrating ductal breast carcinomas. MATERIALS AND METHODS: Two hundred and fifty consecutives women with breast infiltrating ductal carcinomas, aged between 37 and 83 years were included in this study. Serum CA15.3 was determined by electro-chemoluminescence assay (ECLIA-Elecsys 170 Roche). Immunohistochemical staining on tissue sections of 4-5 microns was done by the EnVision method with a heat-induced antigen retrieval step. Antibody used for Bcl2 was (124, Dako, dilution 1/150). Bcl2 expression was assessed as negative (-), weak positive (+) or strong positive (++). RESULTS: In the study group, serum CA15.3 concentrations ranged between 1 and 1743 U/ml, with 25, 50 and 75 percentiles of 12.7, 17.6 and 24.3 U/ml respectively. Serum CA15.3 concentrations were higher in Bcl2 negative cases than in Bcl2 + and Bcl2 ++. We found statistically significant differences between subgroups Bcl2 negative and Bcl2 ++ (p=0.044), between Bcl2 + Bcl2 ++ (p=0.039) and between Bcl2 ++ and Bcl2 -/+ (p=0.013). When we considered 25 U/mL as the threshold of positivity, antigen values>25 U/ml were more frequent in tumors Bcl2- than in Bcl2 ++ (20/52 vs 29/170, p=0.001). The same behavior was observed when comparing the subgroups -/+ with ++ (p=0.001). A very important aspect of our work was that this CA15.3 behavior in relation to the immunohistochemical expression of Bcl2 was maintained in hormone-dependent tumors (ER+), but not in hormone-independent ones. CONCLUSIONS: The results led us to the following consideration: In women affected by infiltrating ductal breast carcinomas, serum levels of CA15.3 associated inversely, both qualitatively and quantitatively, with the immunohistochemical expression of Bcl2, but this fact exists only in hormone-dependent tumors.

[Spanish Society of Anaesthesia (SEDAR) guidelines for pre-anaesthesia checking procedures]. / Directrices de procedimientos de comprobación y validación («chequeo¼) previos a la anestesia de la Sociedad Española de Anestesiología.

We present this document as a guide to preparing a specific institutional pre-anaesthesia checklist, as recommended in the Helsinki declaration on patient safety in anaesthesiology. Also, the recently recommended WHO "safe surgery check-list" includes a check-list for anaesthesia. A working group was established in accordance with the charter of the Spanish Society of Anaesthesiology and Resuscitation (Sociedad Española de Anestesiología y Reanimación [SEDAR]). The new patient safety culture introduced into medicine, and the recommendations of European anaesthesia societies has led us to design and update protocols in order to improve results in this important part of our speciality. We have prepared these recommendations or guidelines using, as examples, updates of pre-anaesthesia check-lists by other American (ASA), British, or Canadian societies of anaesthesia. With that aim, we enlisted the help of anaesthesia ventilator experts and the participation and advice of experienced anaesthesiologists from all parts of Spain. After various corrections and modifications, the document was available at www.sedar.es, so that any anaesthesiologist could propose any correction, or give their opinion. Finally, these guidelines have been approved by the SEDAR Board of Directors, before it was sent for publication in this journal. The aims of this document are to provide: a guideline applicable to all anaesthesia machines, a descriptive pre-anaesthesia check-list that include everything necessary for the anaesthesia procedure, and a resumed check-list to be available in all the anaesthesia machines or other equivalent, but prepared for each institution, which should include anaesthetic equipment and drugs. So, in order to ensure the aims and requirements of the European Board of Anaesthesiology, the European Society of Anaesthesiology, and the WHO are met, each institution should have a protocol for checking equipment and drugs. These guidelines are applicable to any anaesthesia equipment, enabling every institution to develop their own checking protocols, adapted to their anaesthesia machines and their procedures. With the consent of the SEDAR, this group will collaborate with anaesthesia machines providers in order to develop specific checklists for each of their models that will be available at www.sedar.es.

Breast carcinomas with hyperprolactinemia at the time of diagnosis-clinico-biological association.

AIM: To analyse association between preoperative hyperprolactinemia serum levels and clinical and biological features of breast tumors. METHODS: Serum levels of prolactin were measured in 253 women with invasive breast cancer. Clinical and biological parameters analysed were age, size, lymph node involvement, distant metastasis and immunohistochemical expression of estrogen receptor, progesterone receptor, androgen receptor, bcl-2, p53 and Ki67. RESULTS: In ductal carcinomas hyperprolactinemia were associated with high age (p = 0.017), and with bcl-2 + + + expression (p = 0.017). Furthermore, serum prolactin values were significantly higher in bcl-2 +++ cases vs negative (p = 0.029); the same happened when we considered the positivity threshold of 25 ng/mL (p = 0.015). CONCLUSION: Is possible to detect in 6% of infiltrating ductal breast carcinomas hyperprolactinemia (>25 ng/mL), being associated only with increasing age, but not with other clinical or biological factors; and 2) the most surprising data was the association between prolactinemia (qualitative (>25 ng/mL) and quantitative) and intense bcl-2 tissue expression, which suggests that, probably, this (prolactinemia) is not a sign of worse prognosis and evolution.

[The immunohistochemical expression of cyclin B1 is associated with higher SUV in 18F-FDG-PET in non-small cell lung cancer patients. Initial results]. / La expresión inmunohistoquímica de ciclina B1 conlleva mayores valores de SUV en la 18F-FDG-PET de pacientes con carcinomas no microcíticos de pulmón. Primeros resultados.

AIM: to study the expression of cyclin B1 and its possible relationship with the maximum SUV in FDG-PET and MIB1 expression in patients with NSCLC. MATERIALS AND METHODS: 49 patients (15 adenocarcinomas, 27 squamous cell carcinomas and 7 bronchoalveolar carcinomas) were included in this study; the immunohistochemical expression of cyclin B1 was determined using the tissue-array technique. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. RESULTS: cyclin B1 expression was detected in 40 out of 45 cases. The SUV values were higher (p=0.04) in the cyclin B1+ cases than in the negative cases (16.4+/-8.1 vs 10.9+/-6.2). Cyclin B1 expression and SUV values were not correlated with the clinical stage. The expression of cyclin B1+ correlated positively (p<0.0001) with that of MIB1. After univariate analysis, only the cellular proliferation was a prognostic factor (p=0.037). CONCLUSIONS: our results suggest that there is a direct correlation between cyclin B1 expression and max-SUV values in the PET of NSCLC patients. When the association of cyclin B1 with positive MIB1 is also considered, our results support the role of cell proliferation in FDG uptake by the tumour.

[The immunohistochemical expression of cyclooxygenase 2 is inversely associated with (18)F-FDG-PET SUV values in non-small-cell lung cancers. Initial results]. / La expresión inmunohistoquímica intensa de ciclooxigenasa 2 se asocia inversamente con los valores máximos de SUV en la (18)F-FDG-PET de pacientes afectados de carcinomas no microcíticos de pulmón. Relación con otros factores biológicos.

OBJECTIVE: To study the expression of COX-2 and its possible relationship with the maximum standardized uptake value (SUV) in FDG-PET, and EGFR, p16 and MIB1 expression in patients with NSCLC. MATERIAL AND METHOD: 45 patients (12 adenocarcinomas and 33 squamous cell carcinomas) were included in this study; the immunohistochemical expression of COX-2, MIB-1, p16 and EGFR was determined using tissue-array. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. RESULTS: COX-2 expression was detected in 35 out of 45 cases, and was very significant (> ++) in 12 of them. SUV values were lower in the COX-2 > ++ cases that in the remaining cases (13.4 +/- 1.2 vs. 12.9 vs. 17.1 +/- 1.5; p = 0.059). COX-2 > ++ expression and maxSUV values were not correlated with the clinical stage. The expression of COX-2 > ++ was correlated positively with p16 (r = 0.36; p = 0.014) and negatively with MIB1 (r = -0.32; p = 0.041) expression, whereas the SUV was correlated positively with EGFR (r = 0.44; p = 0.004) and negatively with p16 (r = -0.29; p = 0.041) expression. CONCLUSIONS: Our results suggest that: a) the expression of COX-2 > ++ is often found in this kind of lung cancer and is not associated with the clinical stage; b) the maxSUVs were not related to the stage and were lower in COX-2 > ++ tumours than in the other cases; and c) the different behaviour of both parameters can be explained by their correlation with cell proliferation (MIB1), EGFR and p16 expression.

Reduced clinicopathological influence of hormone-dependence on breast carcinomas in women older than 70 years.

In order to evaluate the influence of hormone dependence on the features of infiltrating ductal carcinoma of the breast we have assayed the cytosolic levels of estrogen receptor (ER), progesterone receptor (PR), pS2 and cathepsin D in 53 women aged over 70 years and in 95 women aged between 55 and 70 years. Tumor size, axillary involvement, distant metastasis, histological grade, ploidy and S-phase were taken into account. Carcinomas of women aged over 70 did not show higher concentrations or higher positive results for ER and PR than those of women in the 55-70-year age group. In older patients, negativity for ER was associated only with higher S-phase fraction, while negativity for PR was not associated with any of the parameters analyzed. In the younger subgroup, negativity for ER was associated with larger tumor size, higher S-phase fraction, lymph node involvement, histological grade 3 and lower pS2 values. Negativity for PR was associated with the same parameters, as well as with a higher frequency of recurrence. Our results suggest a reduced influence of hormone dependence on the clinicopathological features of breast carcinomas in patients older than 70 years compared with women aged between 55 and 70 years.

Reduced clinicopathological influence of hormone-dependence on breast carcinomas in women older than 70 years.

In order to evaluate the influence of hormone dependence on the features of infiltrating ductal carcinoma of the breast we have assayed the cytosolic levels of estrogen receptor (ER), progesterone receptor (PR), pS2 and cathepsin D in 53 women aged over 70 years and in 95 women aged between 55 and 70 years. Tumor size, axillary involvement, distant metastasis, histological grade, ploidy and S-phase were taken into account. Carcinomas of women aged over 70 did not show higher concentrations or higher positive results for ER and PR than those of women in the 55-70-year age group. In older patients, negativity for ER was associated only with higher S-phase fraction, while negativity for PR was not associated with any of the parameters analyzed. In the younger subgroup, negativity for ER was associated with larger tumor size, higher S-phase fraction, lymph node involvement, histological grade 3 and lower pS2 values. Negativity for PR was associated with the same parameters, as well as with a higher frequency of recurrence. Our results suggest a reduced influence of hormone dependence on the clinicopathological features of breast carcinomas in patients older than 70 years compared with women aged between 55 and 70 years.

[Preoperative CA15.3 serum levels and cellular proliferation in patients having infiltrating ductal carcinomas of the breast]. / CA15.3 sérico y proliferación celular en carcinomas ductales infiltrantes de mama.

OBJECTIVE: To study the possible correlations between the preoperative CA15.3 serum levels and the cellular proliferation, measured by S-phase (SP), in patients having infiltrating ductal carcinomas (IDC) of the breast MATERIAL AND METHODS: The study group included 79 patients with an age ranged between 39 and 86 yrs (64,8 +/- 11,8). Ploidy and S-phase were measured by cytometry (Fascam. Beckton Dikinson. USA) in fresh samples RESULTS: Using as cut-off for SP the value of 7 %, which represents the median obtained previously in 321 patients with IDC (r: 0,8-51,2; 9,3 +/- 7,9; percentiles 25 y 75; 4,3 y 11,8 %), we can observed that the antigenic levels were higher (p:0,015) in the tumors with low SP. These same behavior was noted when 30U/ml was used as cut-off for CA15.3. Likewise, the levels of the tumor marker increased significantly (p:0,007) when the SP moved from < 4,3 % to 7,1 %, to decrease later (p:0,010) when the SP value was comprised between 7,11 % and 11,8 %. The same behavior of this tumor marker in relation to the SP was noted in tumors without axillary involvement tumors, as well as in aneuploid carcinomas. CONCLUSION: a) Release of CA15.3 happens when SP increases to rise the 7,1 % value, to decrease later although that goes on increasing, and b) The same behaviour of this marker with the S-phase was observed in tumors without axillary involvement, as well as in aneuploid carcinomas.

[Evolution in 18F-FDG-PET of a case of Hodgkin disease, nodular sclerosis variety, after treatment and autotrasplant]. / Evolución, mediante estudios con 18F-FDG, de un caso de enfermedad de Hodgkin tipo esclerosis nodular después de tratamiento y autotrasplante.

Positron Emission Tomography (PET) has become a very useful tool for monitoring Hodgkin's disease patients in the last years. When there is suspicion of disease persistence after treatment, this technique makes it possible to evaluate treatment activity of the residual lesions observed in the CT scan. Furthermore, due to the whole body study, new tumor sites, which very often change the therapeutic option, can be detected. We must take into account, however, that 18F-FDG is a very sensitive but not very specific tumor marker, since some inflammatory or infectious conditions may be associated to significant radiopharmaceutical uptakes. Thus, in order to increase specificity it is mandatory to correlate the PET information with the rest of the conventional imaging and clinical data and evolution of the patient. We present the case of a woman with Hodgkin's disease in which 18F-FDG PET was included in the follow-up. Both conditions, tumor and infection, were present in different times of the course. The integration of all the x-ray, clinical, laboratory and metabolic information allowed for a better and correct management of this patient.

[Application of a critical incident reporting and analysis system in an anesthesiology department]. / Utilización de un sistema de comunicación y análisis de incidentes críticos en un servicio de anestesia.

OBJECTIVES: To ascertain the changes in anesthesia-related morbidity and mortality after application of a scheme for reporting critical incidents and to assess the effect of implementing preventive measures against the detected errors. PATIENTS AND METHODS: We defined a critical incident to be any situation in which the margin of safety for the patient was reduced or might have been reduced. We analyzed data from the period between January 1999 and December 2004. RESULTS: The number of critical incidents was 547 (0.79% of 68627 anesthetic procedures). Human error was identified in 279 incidents (51%). The most frequent factors underlying errors were wrong diagnosis of the situation, communication problems, and failure to check equipment and drugs. The patient suffered no adverse effect in 81.8% of the incidents; 78.9% were considered preventable. Introducing an equipment checklist before anesthesia reduced the number of incidents from 90 events in 21809 cases in 31 months to 34 events out of 22064 cases in 29 months; chi2 test, P < 0.05; odds ratio (OR), 2.68; 95% confidence interval (CI), 1.80-3.98). Labeling syringes reduced errors in the administration of medications from 45 errors in 21 809 cases in 31 months to 27 in 22064 cases in 29 months; chi2, P < 0.05; OR, 1.68; 95% CI, 1.04-2.72. CONCLUSIONS: Corrective measures were adopted as a result of the incident reporting scheme. Some of the measures led to a statistically significant reduction in equipment and drug administration errors.

[Incident reporting systems and patient safety in anesthesia]. / Sistemas de comunicación de incidentes y seguridad del paciente en anestesia.

Incident reporting schemes collect information on adverse events, errors, complications, or problems with the aim of analyzing their causes and suggesting changes to prevent recurrence. Such schemes are currently part of clinical safety programs in various countries. Although the ideal form for a reporting system is debated, an essential part of its success will be the establishment of a culture of safety within an organization. The underlying assumption is that even though errors are an inherent part of a process that relies on human beings, they are nearly always favored by a chain of system failures. Therefore, reporting is intended to stimulate a culture of learning rather than assigning blame. The main limitations of such schemes are under reporting, the use of different terms and concepts, the lack of resources for research and development, and the scarcity or lack of legislation to guarantee the proper use of information without legal consequences.

[Preoperative serum CA15.3 and CEA levels and clinical-biological parameters in breast tumors]. / Concentraciones séricas preoperatorias de antígeno carbohidrato 15.3 y antígeno carcinoembrionario y características clínico-biológicas tisulares de los carcinomas mamarios.

OBJECTIVE: To study the possible associations between preoperative serum CEA and CA15.3 levels and different clinical-biological parameters of infiltrating ductal carcinomas of the breast (IDC). PATIENTS AND METHOD: Preoperative serum CA15.3 and CEA levels were determined in 255 and 224 females, respectively, having IDC. We assayed the cytosolic levels of estrogen receptor, pS2, cathepsin D and hyaluronic acid, as well as the levels of epidermal growth factor receptor in cell surfaces. Tumor size, axillary involvement (N), distant metastasis (M), histological grade (HG) and cellular S-phase (SP) were taken into account. RESULTS: 22 IDC were positive for CA15.3 (> 40 U/ml) and they had greater global tumor size (p < 0.001), > 2 cm (p: 0.005) and distant metastasis (p < 0.001). 19 IDC were positive for CEA (> 4 ng/ml) and they had greater global tumor size (p < 0.001), > 2 cm (p < 0.001), > 5 cm (p: 0.052) and global S-phase values (p: 0.062), and were more frequently N + (p: 0.045), > 3N + (p: 0.001) and > 10N + (p < 0.001), M + (p: 0.004), HG3 (p: 0.091) and SP > 7 % (p: 0.006). CONCLUSIONS: Our results led us to the following: In patients having IDC of the breast, preoperative serum CA15.3 levels are associated with greater tumor size and distant metastasis, while pre-treatment CEA serum levels are associated moreover with axillary involvement; we have not observed any correlation between serum levels of both antigens and the hormonal status of the tumor; these results had physiopathological interest but reduced clinical value in pretreatment breast carcinomas due to their low sensitivity of both markers. However, they are useful in the follow-up of the patients when assessing serum concentrations of both markers, since they contribute to knowing the patients' clinical status better.

[Expression of epidermal growth factor receptor (EGFR) in hormone-independent breast cancers]. / La expresión del receptor del factor de crecimiento epidérmico (EGFR) en carcinomas mamarios hormonoindependientes.

OBJECTIVE: To determine the expression of epidermal growth factor receptor (EGFR) in ER-negative and Pg-R negative infiltrating ductal carcinomas of the breast (IDC) and to analyze the possible relationship between the EGFR positivity and some clinico-biological parameters of tumors. MATERIAL AND METHODS: EGFR was measured by a single point radioligand assay in the cell surfaces of 115 ER-negative and Pg-R-negative (< 10 fmol/mg prot.) IDC. We measured also the cytosolic concentrations of pS2, cathepsin D, tissue-type plasminogen activator (t-PA) and hyaluronic acid (AH), as well as the levels of AH in cell surfaces. Tumor size, axillary involvement, distant metastasis, histological grading, ploidy and S-phase (SP) were taken account. RESULTS: Using as cut-off for EGFR a value of 5 fmol/mg prot., we can observed that IDCs -EGFR + had greater global values of S-phase (p: 0.005) and were more frequently metastastatic (p: 0.004), SP > 7 % (p < 0.001) and SP > 14 % (p: 0.077); likewise, they were lower frequently pS2-positive (p < 0.01) and t-PA-positive (p < 0.01). During the follow up time (median 85 months), the number of recurrences was higher in EGFR-positive than in EGFR- negative tumors (14/41 frente a 1/29; p: 0.002), but there was not differences in the number of deaths by the tumor. CONCLUSIONS: 1) The EGFR-positivity in ER-negative and PgR-negative IDCs is associated with distant metastasis, greater cellular proliferation (SP), lower positivity for pS2 and t-PA and greater number of recurrences. 2) Using 10 fmol/mg prot. as cut-off, we observed the same findings, except the change in cellular proliferation. 3) Our findings support the possible use of EGFR as a prognostic parameter in those breast carcinomas.