Immunotherapy in patients with brain metastasis: advances and challenges for the treatment and the application of circulating biomarkers.

The central nervous system (CNS) is one of the most frequent metastatic sites of various cancers, including lung cancer, breast cancer and melanoma. The development of brain metastases requires a specific therapeutic approach and is associated with high mortality and morbidity in cancer patients. Advances in precision medicine and the introduction in recent years of new drugs, such as immunotherapy, have made it possible to improve the prognosis of these patients by improving survival and quality of life. New diagnostic techniques such as liquid biopsy allow real-time monitoring of tumor evolution, providing molecular information on prognostic and predictive biomarkers of response to treatment in blood or other fluids. In this review, we perform an exhaustive update of the clinical trials that demonstrate the utility of immunotherapy in patients with brain metastases and the potential of circulating biomarkers to improving the results of efficacy and toxicity in this subgroup of patients.

Discovery of Gamma Rays from the Quiescent Sun with HAWC.

We report the first detection of a TeV γ-ray flux from the solar disk (6.3σ), based on 6.1 years of data from the High Altitude Water Cherenkov (HAWC) observatory. The 0.5-2.6 TeV spectrum is well fit by a power law, dN/dE=A(E/1 TeV)^{-γ}, with A=(1.6±0.3)×10^{-12} TeV^{-1} cm^{-2} s^{-1} and γ=3.62±0.14. The flux shows a strong indication of anticorrelation with solar activity. These results extend the bright, hard GeV emission from the disk observed with Fermi-LAT, seemingly due to hadronic Galactic cosmic rays showering on nuclei in the solar atmosphere. However, current theoretical models are unable to explain the details of how solar magnetic fields shape these interactions. HAWC's TeV detection thus deepens the mysteries of the solar-disk emission.

Clinical, molecular, and immune correlates of the Immunotherapy Response Score in patients with advanced urothelial carcinoma under atezolizumab monotherapy: analysis of the phase II IMvigor210 trial.

BACKGROUND: In the advanced urothelial carcinoma (aUC) scenario there are no consistent immune checkpoint blockade predictive biomarkers. Recently a novel pan-tumor molecular tissue-based biomarker, the Immunotherapy Response Score (IRS), has been proposed. We conducted a retrospective study to validate the prognostic/predictive utility of the IRS in patients with aUC under atezolizumab monotherapy and to characterize its underlying molecular/immune features in the context of the IMvigor210 phase II trial. PATIENTS AND METHODS: This is a post hoc pooled analysis of 261 patients with available clinical, molecular, and immune tumor data treated with atezolizumab monotherapy in the IMvigor210 phase II clinical trial. Efficacy endpoints were overall survival (OS), disease control rate (DCR), and overall response rate (ORR). Survival estimates were calculated by the Kaplan-Meier method, and groups were compared with the log-rank test. The Cox proportional hazards regression model was used to evaluate factors independently associated with OS. Factors associated with disease control (DC) and response were tested with logistic regression in univariable and multivariable analyses. Comparisons between patient and disease characteristics were carried out using chi-square or Fisher's exact tests. All P values were two-sided, and those <0.05 were considered statistically significant. RESULTS: High IRS was significantly associated with a better OS in univariable [hazard ratio (HR) = 0.49, P < 0.001] and multivariable (HR = 0.60, P = 0.018) analyses. DCR and ORR were significantly higher among high IRS patients (DCR for high IRS versus low IRS patients: 57% versus 32%, P < 0.001; ORR: 42% versus 10%, P < 0.001). High IRS patients presented a higher probability of DC and response in univariable [DC: odds ratio (OR) = 2.72, P < 0.001; response: OR = 3.92, P < 0.001] and multivariable (DC: OR = 2.72, P < 0.001; response: OR = 3.92, P < 0.001) analyses. CONCLUSIONS: This study validates IRS as a strong independent prognostic and predictive biomarker for OS and DC/response in patients with aUC treated with atezolizumab monotherapy in the IMvigor210 phase II clinical trial.

Graves' disease induced by Alemtuzumab in relapsing-remitting multiple sclerosis patients: an observational study in a reference center.

OBJECTIVES: Graves' disease induced by Alemtuzumab (GD-IA) is one of the most frequently observed adverse events in patients with multiple sclerosis (MS) treated with this drug. The aim of this study is the sequencing and description of these events, along with the identification of the risk factors leading to their development. MATERIALS AND METHODS: We conducted a retrospective observational study identifying patients with relapsing-remitting multiple sclerosis (RRMS) and GD-IA, studying their baseline clinical features and variables related to the natural history of the disease. RESULTS: A total of 121 participants treated with Alemtuzumab were included, of whom 41 developed GD-IA (33.9%). A higher percentage of first-degree relatives with autoimmune thyroid disease was documented in the subgroup who developed the abovementioned event (14.6% vs 1.5%; p < 0.01). A total of 70.7% of patients diagnosed with GD-IA (n = 29/41) had fluctuations in thyroid function during follow-up, and 24.4% (n = 10/41) required total thyroidectomy for resolution of the condition. In 54.8% of participants diagnosed with GD-IA, a pattern of significant TSH decline was identified in the month prior to diagnosis of the event, with high predictive ability and associated with a more favorable clinical course (fewer weeks to normalization of thyroid function, HR = 8.99; 95% CI [2.11-38.44]; p = 0.0003). CONCLUSION: GD-IA has an atypical course compared to classical forms of the disease. The identification of risk factors for the development of the disease before starting treatment with Alemtuzumab and early monitoring of thyroid function once this treatment is initiated prove to be useful strategies in the diagnosis and clinical management of this condition.

Improvements in the Effectiveness of Early Detection in Colorectal Cancer with Open-Label Randomised Study.

INTRODUCTION: The general objective of this research is to improve the quality of colorectal cancer screening (CRC) by assessing, as an indicator of effectiveness, the ability of colonoscopy to detect more advanced adenomas in the exposed group than in the control group. MATERIAL AND METHODS: The present work is designed as an open-label randomized study on cancer screening, using two groups based on their exposure to the protocol: an exposed to intervention group (EIG, 167), and a control group (CG, 167), without the intervention of the protocol and by 1:1 matching. RESULTS: In 167 patients in the GEI, 449 polyps are visualized and 274 are adenomas (80.58%), of which 100 (36.49%) are advanced adenomas. In the CG (n = 174), there are 321 polyps and 152 adenomas (82.60%). The variables significantly associated by logistic regression to the detection of adenomas are the male sex with an OR of 2.52. The variable time to withdrawal, ≥9 min, is significant at 99% confidence (p = 0.002/OR 34.67) and the fractional dose is significant at 99% (p = 0.009, OR 7.81). CONCLUSION: Based on the observations made, our study suggests that the intervention in collaboration between primary care and hospital care is effective from a preventive point of view and achieves the objective of effectiveness and quality of the PCCR.

Constraints on Lorentz Invariance Violation from HAWC Observations of Gamma Rays above 100 TeV.

Because of the high energies and long distances to the sources, astrophysical observations provide a unique opportunity to test possible signatures of Lorentz invariance violation (LIV). Superluminal LIV enables the decay of photons at high energy. The high altitude water Cherenkov (HAWC) observatory is among the most sensitive gamma-ray instruments currently operating above 10 TeV. HAWC finds evidence of 100 TeV photon emission from at least four astrophysical sources. These observations exclude, for the strongest of the limits set, the LIV energy scale to 2.2×10^{31} eV, over 1800 times the Planck energy and an improvement of 1 to 2 orders of magnitude over previous limits.

Applicability and limitations of the radon-deficit technique for the preliminary assessment of sites contaminated with complex mixtures of organic chemicals: A blind field-test.

A blind field test with 136 independent measurements of radon (222Rn) in soil air retrieved from a depth of 0.8 m in a decommissioned lindane (γ-hexachlorocyclohexane) production plant was undertaken to evaluate the performance of the 222Rn-deficit technique as a screening methodology for the location and delineation of subsurface accumulations of complex mixtures of organic contaminants. Maps of 222Rn iso-concentrations were drawn and interpreted before direct analytical information regarding concentrations of hexachlorocyclohexanes, chlorobenzenes and BTEX compounds in soil, groundwater and soil air were disclosed to the authors. The location and extension of pollution hot spots inferred from the 222Rn campaigns agrees remarkably well with the analytical data obtained from the intrusive sampling campaigns and with the location of contaminant source zones (chemical reactor and waste-storage area) and geological sinks of those contaminants (paleochannel). Two main limitations to the applicability of the 222Rn-deficit technique were identified and assessed: The statistically significant variation of 222Rn concentrations with diurnal changes of ground-level air temperature and the maximum depth of investigation in the absence of significant advective and co-advective transport of radon. If the influence of those two factors is accounted for and/or minimized (by averaging replicated measurements during the workday and in different days), the 222Rn-deficit technique has the potential to be an efficient technique which delivers information in quasi-real time, with a much higher spatial density than that of intrusive techniques, at a much faster rate and at a significantly lower cost. MAIN FINDINGS: The 222Rn-deficit technique is an effective tool for real-time site characterization only limited by diffusion length of radon and diurnal temperature variations.

Multiple Galactic Sources with Emission Above 56 TeV Detected by HAWC.

We present the first catalog of gamma-ray sources emitting above 56 and 100 TeV with data from the High Altitude Water Cherenkov Observatory, a wide field-of-view observatory capable of detecting gamma rays up to a few hundred TeV. Nine sources are observed above 56 TeV, all of which are likely galactic in origin. Three sources continue emitting past 100 TeV, making this the highest-energy gamma-ray source catalog to date. We report the integral flux of each of these objects. We also report spectra for three highest-energy sources and discuss the possibility that they are PeVatrons.

Publisher Correction: Very-high-energy particle acceleration powered by the jets of the microquasar SS 433.

In this Letter, owing to a production error, the penultimate version of the PDF was published. The HTML version was always correct. The PDF has been corrected online.

Concurrent chemoradiation for locally advanced stage III non-small cell lung cancer with cisplatin, vinorelbine, and thoracic radiotherapy: a phase II study from the Galician Lung Cancer Group

Purpose: The aim of this phase II study was to evaluate the activity and safety of the combination of cisplatin and vinorelbine with thoracic radiotherapy in unresectable locally advanced stage III non-small cell lung cancer (NSCLC). The primary endpoint was the objective response rate (ORR). Secondary objectives included toxicity profile, progression-free survival (PFS), and overall survival (OS). Materials and methods: A total of 48 NSCLC patients were enrolled (median age 60 years, 52% stage IIIA and 48% stage IIIB, 52% adenocarcinoma). Patients received three cycles of chemotherapy every 21 days [intravenous cisplatin 80 mg/m2 and intravenous vinorelbine 25 mg/m2 on day 1 and oral vinorelbine on day 8 (60 mg/m2)] concurrent with radiotherapy (66 Gy, administered at 1.8 Gy per day, five consecutive days per week). Results: ORR was 79.2% (72.9% showing partial response and 6.3% showing complete response). With a median follow-up of 20.7 months, median PFS was 12 months and median OS was 36 months. Grade 3/4 toxicities were: neutropenia (14.5%), anaemia (6.2%), vomiting (2%), and oesophagitis (4.2%). No toxic deaths were reported. Conclusion: This combined regimen shows efficacy and a manageable safety profile. PFS and OS outcomes are encouraging and warrant further research

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Very-high-energy particle acceleration powered by the jets of the microquasar SS 433.

SS 433 is a binary system containing a supergiant star that is overflowing its Roche lobe with matter accreting onto a compact object (either a black hole or neutron star)1-3. Two jets of ionized matter with a bulk velocity of approximately 0.26c (where c is the speed of light in vacuum) extend from the binary, perpendicular to the line of sight, and terminate inside W50, a supernova remnant that is being distorted by the jets2,4-8. SS 433 differs from other microquasars (small-scale versions of quasars that are present within our own Galaxy) in that the accretion is believed to be super-Eddington9-11, and the luminosity of the system is about 1040 ergs per second2,9,12,13. The lobes of W50 in which the jets terminate, about 40 parsecs from the central source, are expected to accelerate charged particles, and indeed radio and X-ray emission consistent with electron synchrotron emission in a magnetic field have been observed14-16. At higher energies (greater than 100 gigaelectronvolts), the particle fluxes of γ-rays from X-ray hotspots around SS 433 have been reported as flux upper limits6,17-20. In this energy regime, it has been unclear whether the emission is dominated by electrons that are interacting with photons from the cosmic microwave background through inverse-Compton scattering or by protons that are interacting with the ambient gas. Here we report teraelectronvolt γ-ray observations of the SS 433/W50 system that spatially resolve the lobes. The teraelectronvolt emission is localized to structures in the lobes, far from the centre of the system where the jets are formed. We have measured photon energies of at least 25 teraelectronvolts, and these are certainly not Doppler-boosted, because of the viewing geometry. We conclude that the emission-from radio to teraelectronvolt energies-is consistent with a single population of electrons with energies extending to at least hundreds of teraelectronvolts in a magnetic field of about 16 microgauss.

Concurrent chemoradiation for locally advanced stage III non-small cell lung cancer with cisplatin, vinorelbine, and thoracic radiotherapy: a phase II study from the Galician Lung Cancer Group.

PURPOSE: The aim of this phase II study was to evaluate the activity and safety of the combination of cisplatin and vinorelbine with thoracic radiotherapy in unresectable locally advanced stage III non-small cell lung cancer (NSCLC). The primary endpoint was the objective response rate (ORR). Secondary objectives included toxicity profile, progression-free survival (PFS), and overall survival (OS). MATERIALS AND METHODS: A total of 48 NSCLC patients were enrolled (median age 60 years, 52% stage IIIA and 48% stage IIIB, 52% adenocarcinoma). Patients received three cycles of chemotherapy every 21 days [intravenous cisplatin 80 mg/m2 and intravenous vinorelbine 25 mg/m2 on day 1 and oral vinorelbine on day 8 (60 mg/m2)] concurrent with radiotherapy (66 Gy, administered at 1.8 Gy per day, five consecutive days per week). RESULTS: ORR was 79.2% (72.9% showing partial response and 6.3% showing complete response). With a median follow-up of 20.7 months, median PFS was 12 months and median OS was 36 months. Grade 3/4 toxicities were: neutropenia (14.5%), anaemia (6.2%), vomiting (2%), and oesophagitis (4.2%). No toxic deaths were reported. CONCLUSION: This combined regimen shows efficacy and a manageable safety profile. PFS and OS outcomes are encouraging and warrant further research.

State-trait anxiety levels during pregnancy and foetal parameters following intervention with music therapy.

BACKGROUND: Research indicates that anxiety during pregnancy may be a risk factor for the development of alterations in the mental health of the pregnant woman and of obstetric complications. OBJECTIVE: to investigate the effect of music therapy on maternal anxiety, before and after a non-stress test (NST), and the effect of maternal anxiety on the birthing process and birth size. METHODS: 409 nulliparous women coming for routine prenatal care were randomized in the third trimester to receive either music therapy (n = 204) or no music therapy (n = 205) during an NST. Maternal anxiety was assessed using the Spielberger State-Trait Anxiety Inventory before and after the NST. RESULTS: After the NST, the women from the music group showed significantly lower scores in state anxiety (OR = 0.87; p < 0.001) as well as trait anxiety (p < 0.001) than the control group. Furthermore, the pregnant women from the music group presented lower levels of state-trait anxiety than the control group in relation to the variables of birth process, and higher birth weight and chest circumference in the newborn (OR = 3.5 and OR = 0.81, respectively; p < 0.05). LIMITATIONS: This study was limited by the fact that it was a single-centre study; the observers conducting the NST were not blinded to the allocation, although neither midwife had any knowledge of the maternal anxiety scores, and we could not apply the double-blind method due to the nature of the observation. CONCLUSIONS: Our findings confirm that music therapy intervention during pregnancy could reduce elevated state-trait anxiety levels during the third trimester. Further research into the influence of music therapy as intervention on maternal anxiety and on the birthing process and birth size is required during pregnancy.

Environmental risk assessment of cobalt and manganese from industrial sources in an estuarine system.

A total of 74 samples of soil, sediment, industrial sludge, and surface water were collected in a Mediterranean estuarine system in order to assess the potential ecological impact of elevated concentrations of Co and Mn associated with a Terephthalic (PTA) and Isophthalic (PIPA) acids production plant. Samples were analyzed for elemental composition (37 elements), pH, redox potential, organic carbon, and CaCO3 content, and a group of 16 selected samples were additionally subjected to a Tessier sequential extraction. Co and Mn soil concentrations were significantly higher inside the industrial facility and around its perimeter than in background samples, and maximum dissolved Co and Mn concentrations were found in a creek near the plant's discharge point, reaching values 17,700 and 156 times higher than their respective background concentrations. The ecological risk was evaluated as a function of Co and Mn fractionation and bioavailability which were controlled by the environmental conditions generated by the advance of seawater into the estuarine system during high tide. Co appeared to precipitate near the river mouth due to the pH increase produced by the influence of seawater intrusion, reaching hazardous concentrations in sediments. In terms of their bioavailability and the corresponding risk assessment code, both Co and Mn present sediment concentrations that result in medium to high ecological risk whereas water concentrations of both elements reach values that more than double their corresponding Secondary Acute Values.

Effects of prenatal music stimulation on state/trait anxiety in full-term pregnancy and its influence on childbirth: a randomized controlled trial.

BACKGROUND: Many researchers have pointed out the strong relationship between maternal psychological well-being and fetal welfare during pregnancy. The impact of music interventions during pregnancy should be examined in depth, as they could have an impact on stress reduction, not only during pregnancy but also during the course of delivery, and furthermore induce fetal awareness. OBJECTIVE: This study aimed to investigate the effect of music on maternal anxiety, before and after a non-stress test (NST), and the effect of music on the birthing process. MATERIAL AND METHOD: The four hundred and nine pregnant women coming for routine prenatal care were randomized in the third trimester to receive either music (n = 204) or no music (n = 205) stimulation during an NST. The primary outcome was considered as the maternal state anxiety score before and after the NST, and the secondary outcome was the birthing process. RESULTS: Before their NST, full-term pregnant women who had received music intervention were found to have a similar state-trait anxiety score to those from the control group, with 38.10 ± 8.8 and 38.08 ± 8.2, respectively (p = .97). After the NST, the mean state-trait anxiety score of each group was recorded, with results of 30.58 ± 13.2 for those with music intervention, and 43.11 ± 15.0 for those without music intervention (p < .001). In the control group, the NST was followed by a statistically significant increase in the state-trait anxiety score (38.08 ± 8.2 versus 43.11 ± 15.0, p < .001). However, listening to music during the NST resulted in a statistically significant decrease in the state-trait anxiety score of the study group (38.10 ± 8.8 versus 30.58 ± 13.2, OR = 0.87, p < .001). Furthermore, the first stage of labor was shorter in women who received music stimulation (OR = 0.92, p < .004). They also presented a more natural delivery beginning (spontaneous) and less medication (stimulated and induced) than those who were not stimulated musically, with statistically significant differences (p < .01). CONCLUSIONS: Prenatal music intervention could be a useful and effective tool to reduce anxiety in full-term pregnant women during an NST and improve the delivery process by reducing the first stage of labor in nulliparous women.

Extended gamma-ray sources around pulsars constrain the origin of the positron flux at Earth.

The unexpectedly high flux of cosmic-ray positrons detected at Earth may originate from nearby astrophysical sources, dark matter, or unknown processes of cosmic-ray secondary production. We report the detection, using the High-Altitude Water Cherenkov Observatory (HAWC), of extended tera-electron volt gamma-ray emission coincident with the locations of two nearby middle-aged pulsars (Geminga and PSR B0656+14). The HAWC observations demonstrate that these pulsars are indeed local sources of accelerated leptons, but the measured tera-electron volt emission profile constrains the diffusion of particles away from these sources to be much slower than previously assumed. We demonstrate that the leptons emitted by these objects are therefore unlikely to be the origin of the excess positrons, which may have a more exotic origin.

Effects of prenatal music stimulation on fetal cardiac state, newborn anthropometric measurements and vital signs of pregnant women: A randomized controlled trial.

BACKGROUND: Music has been used for medicinal purposes throughout history due to its variety of physiological, psychological and social effects. OBJECTIVE: To identify the effects of prenatal music stimulation on the vital signs of pregnant women at full term, on the modification of fetal cardiac status during a fetal monitoring cardiotocograph, and on anthropometric measurements of newborns taken after birth. MATERIAL AND METHOD: A randomized controlled trial was implemented. The four hundred and nine pregnant women coming for routine prenatal care were randomized in the third trimester to receive either music (n = 204) or no music (n = 205) during a fetal monitoring cardiotocograph. All of the pregnant women were evaluated by measuring fetal cardiac status (basal fetal heart rate and fetal reactivity), vital signs before and after a fetal monitoring cardiotocograph (maternal heart rate and systolic and diastolic blood pressure), and anthropometric measurements of the newborns were taken after birth (weight, height, head circumference and chest circumference). RESULTS: The strip charts showed a significantly increased basal fetal heart rate and higher fetal reactivity, with accelerations of fetal heart rate in pregnant women with music stimulation. After the fetal monitoring cardiotocograph, a statistically significant decrease in systolic blood pressure, diastolic blood pressure and heart rate in women receiving music stimulation was observed. CONCLUSION: Music can be used as a tool which improves the vital signs of pregnant women during the third trimester, and can influence the fetus by increasing fetal heart rate and fetal reactivity.

Early in vitro development of daptomycin non-susceptibility in high-level aminoglycoside-resistant Enterococcus faecalis predicts the efficacy of the combination of high-dose daptomycin plus ampicillin in an in vivo model of experimental endocarditis.

Background: Previous studies showed development of daptomycin non-susceptibility (DNS: MIC >4 mg/L) in Enterococcus faecalis infections. However, no studies have assessed the efficacy of the combination of daptomycin/ampicillin against E. faecalis strains developing DNS in the experimental endocarditis (EE) model. Objectives: To assess the in vitro and in vivo efficacy of daptomycin at 10 mg/kg/day, daptomycin/ampicillin and ampicillin/ceftriaxone against two high-level aminoglycoside-resistant E. faecalis strains, one developing DNS after in vitro exposure to daptomycin and another that did not (DS). Methods: Subculture of 82 E. faecalis strains from patients with endocarditis with daptomycin MICs, time-kill and in vivo experiments using the EE model. Results: 33% of the strains (27 of 82) displayed DNS after subculture with daptomycin. Daptomycin MIC rose from 0.5-2 to 8-16 mg/L. In time-kill experiments, when using a high inoculum (10 8 cfu/mL), daptomycin/ampicillin was synergistic for one-third of DS strains and none of DNS strains, while ampicillin/ceftriaxone retained synergy in all cases. In the EE model, daptomycin did not significantly reduce cfu/g from vegetations compared with control against either strain, while daptomycin/ampicillin reduced significantly more cfu/g than daptomycin against the DS strain, but not against the DNS strain [2.9 (2.0-4.1) versus 6.1 (4.5-8.0); P = 0.002]. Ampicillin/ceftriaxone was synergistic and bactericidal against both strains, displaying the same activity as daptomycin/ampicillin against the DS strain. Conclusions: Performance of an Etest for daptomycin MIC after subculture with daptomycin inhibitory doses on strains of high-level aminoglycoside-resistant E. faecalis endocarditis may be an easy test to predict the in vivo efficacy of daptomycin/ampicillin.

Epidermal growth factor receptor expression in gastric tumors and its relationship with the germline polymorphisms - 216 G>T, -191 C>A, (CA) n IVS1, and R521K.

BACKGROUND: Gastric cancer (GC) is the third worldwide leading cause of cancer-related death affecting both sexes. The aberrant expression of epidermal growth factor receptor (EGFR) gene has been detected in many human epithelial malignancies and linked to advanced disease, more aggressive phenotype, and poor prognosis. AIMS: To analyze the relation that the expression of EGFR in gastric tumors holds with pathological characteristics and with the germline polymorphisms -216 G>T, -191 C>A, (CA) n IVS1, and R521K. MATERIALS AND METHODS: We studied 22 biopsies from gastric tumors obtained by endoscopy. EGFR expression was determined by relative quantification real-time polymerase chain reaction with the glyceraldehyde-3-phosphate dehydrogenase reference gene (as for messenger RNA [mRNA]) and by immunohistochemistry (IHC) (as for protein). EGFR germline polymorphisms were analyzed by sequencing, GeneScan, and restriction fragment length polymorphisms. RESULTS: EGFR mRNA expression was increased (>2-fold) in 13.6% of GC cases, decreased (<0.5-fold) in 68.2%, and normal in 18.2%; overexpression was related to well-differentiated gastric tumors, whereas underexpression was linked to moderate or poorly differentiated gastric tumors (P < 0.001). EGFR protein expression was high (IHC 2+ and 3+) in 29.4% of gastric tumors and was normal or low (score 0 to 1+) in 70.6% cases. EGFR expression, in both mRNA and protein, was not related to any EGFR polymorphism (P > 0.05). CONCLUSIONS: Most gastric tumors showed low EGFR expression (mRNA and protein), whereas EGFR overexpression was related to well-differentiated gastric tumors. Furthermore, germinal polymorphisms -216, -191, (CA) n IVS1, and R521K were not related to EGFR expression (mRNA or protein).