Estimation of neutron-equivalent dose in organs of patients undergoing radiotherapy by the use of a novel online digital detector.

Neutron peripheral contamination in patients undergoing high-energy photon radiotherapy is considered as a risk factor for secondary cancer induction. Organ-specific neutron-equivalent dose estimation is therefore essential for a reasonable assessment of these associated risks. This work aimed to develop a method to estimate neutron-equivalent doses in multiple organs of radiotherapy patients. The method involved the convolution, at 16 reference points in an anthropomorphic phantom, of the normalized Monte Carlo neutron fluence energy spectra with the kerma and energy-dependent radiation weighting factor. This was then scaled with the total neutron fluence measured with passive detectors, at the same reference points, in order to obtain the equivalent doses in organs. The latter were correlated with the readings of a neutron digital detector located inside the treatment room during phantom irradiation. This digital detector, designed and developed by our group, integrates the thermal neutron fluence. The correlation model, applied to the digital detector readings during patient irradiation, enables the online estimation of neutron-equivalent doses in organs. The model takes into account the specific irradiation site, the field parameters (energy, field size, angle incidence, etc) and the installation (linac and bunker geometry). This method, which is suitable for routine clinical use, will help to systematically generate the dosimetric data essential for the improvement of current risk-estimation models.

Characterization of breast cancer subtypes by quantitative assessment of biological parameters: relationship with clinicopathological characteristics, biological features and prognosis.

OBJECTIVES: Gene expression analysis has identified several breast cancer subtypes, including luminal, epidermal growth factor receptor-2 positive (HER2+), and basal-like. To determine if our proposed molecular taxonomy correlates with biological and clinical behavior. This is based on four biological markers: estrogen and progesterone receptors (ER and PR, respectively), HER2 and the epidermal growth factor receptor-1 (HER1), all of them being determined by quantitative assays. STUDY DESIGN: The biological parameters were examined by enzyme immunoassay, radioligand-binding assay or ELISA, in tumors from 787 patients with invasive breast cancer. Patients were prospectively evaluated over a median follow-up period of 50 months. Subtype definitions were as follows: luminal (ER+), HER2+ (HER2+, ER-, PgR-) and basal-like (HER2-, ER-, PgR-). In addition, we divided basal tumors into two groups based on their HER1 status. RESULTS: A 55.8% of tumors were of luminal type, 11.9% basal-like HER1+, 10.7 basal-like HER1-, and the remainder 21.6% HER2+. Both HER2+ and basal-like subtypes were more frequent in younger and premenopausal women, showing a higher percentage of cases of poorly differentiated tumors and higher S-phase fraction, when compared with those of luminal subtype. Multivariate analysis demonstrated that the subtype of tumor was related to both relapse and overall survival, being those of luminal subtype associated with the best prognosis. CONCLUSIONS: Through the classification of breast tumors in four groups, according to their ER, PgR, HER2 and HER1 status, it is possible to obtain a major division of breast tumors associated with significant differences in biological features and clinical behavior.

Overexpression of matrix metalloproteinases and their inhibitors in mononuclear inflammatory cells in breast cancer correlates with metastasis-relapse.

An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinase (MMP)-1, -2, -7, -9, -11, -13 and -14, tissular inhibitors of metalloproteinase (TIMP)-1, -2 and -3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast were performed. To identify specific groups of tumours with distinct expression profiles the data were analysed by unsupervised hierarchical cluster analysis by each cellular type. We did not find well-defined cluster of cases for tumour cells or fibroblastic cells. However, for mononuclear inflammatory cells the dendogram shows a first-order division of the tumours into two distinct MMP/TIMP molecular profiles, designated group 1 (n=89) and group 2 (n=42). Matrix metalloproteinase-7, -9, -11, -13 and -14, and TIMP-1 and -2, were identified as showing significant high expression in group 2 compared with group 1. Multivariate analysis demonstrated that clustering for mononuclear inflammatory cells was the most potent independent factor associated with distant relapse-free survival (group 2: 5.6 (3.5-9.6), P<0.001). We identify a phenotype of mononuclear inflammatory cells infiltrating tumours, which is associated with the development of distant metastasis. Therefore, this finding suggests that these host inflammatory cells could be a possible target for inhibition of metastasis.

On the use of LiF TLD-600 in neutron-gamma mixed fields.

A new procedure allowing the separate estimation of neutron and gamma dose in mixed radiation fields has been developed in our laboratory. In this communication, a description of the main features of the discrimination procedure and some preliminary results obtained by its use are presented. The procedure is based on the significantly different structure of the glow curve of LiF TLD-600 produced by neutron and gamma radiation. The use of peak resolving numerical methods, sometimes called deconvolution, for the analysis of the glow curves from controlled irradiations at absorbed doses in the range 10-300 mGy with different neutron and gamma proportions, permits to quantify the differences peak by peak, also characterising the well-known neutron quasi-exclusive contribution to the high temperature region, above peak 5. From this study, it was possible to propose a n/gamma TL factor by which the respective doses can be estimated through a simplified analysis, not peak resolving, of the particular features of the glow curves obtained in field measurements. A first set of rather satisfactory results have been obtained by irradiating TLD-600 together with TLD-700 chips using Am-Be sources with different degree of moderation and using lead absorbers to change the gamma component. This component is directly measured by the TLD-700 detectors, allowing the testing of the gamma estimation reached by the discrimination procedure applied to the TLD-600 glow curve.

Study of matrix metalloproteinases and their inhibitors in breast cancer.

An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinases (MMPs) 1, 2, 7, 9, 11, 13, 14, and their tisullar inhibitors (TIMPs) 1, 2, and 3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast (65 with and 66 without distant metastasis) and controls were performed. Staining results were categorised using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically. We observed a broad variation of the total immunostaining scores and the cell type expressing each protein. There were multiple and significant associations between the expression of the different MMPs and TIMPs evaluated and some parameters indicative of tumour aggressiveness, such as large tumour size, advanced tumour grade, high Nottinham prognostic index, negative oestrogen receptor status, peritumoural inflammation, desmoplastic reaction, and infiltrating tumoural edge. Likewise, the detection of elevated immunohistochemical scores for MMP-9, 11, TIMP-1, and TIMP-2, was significantly associated with a higher rate of distant metastases. The expression of MMP-9 or TIMP-2 by tumour cells, MMP-1, 7, 9, 11, 13, or TIMP-3 by fibroblastic cells, and MMP-7, 9, 11, 13, 14, TIMP-1, or TIMP-2 by mononuclear inflammatory cells, was also significantly associated with a higher rate of distant metastases.

Cytosolic levels of TFF1/pS2 in breast cancer: Their relationship with clinical-pathological parameters and their prognostic significance.

BACKGROUND: The Trefoil Factor 1 (TFF1/pS2), a peptide consisting of 60 amino acids, is the most abundant estrogen-induced messenger RNA present in MCF-7 breast cancer cells. The objective of this work was to evaluate the cytosolic TFF1 content in breast carcinomas, its possible relationship with different clinical-pathological parameters, and its potential prognostic significance and predictive value. METHODS: Cytosolic TFF1 levels were examined by immunoradiometric assay in 1031 patients with invasive breast cancer. The median follow-up period was of 50 months. RESULTS: There was a wide variability of cytosolic TFF1 levels in tumors (0.9-743.2 ng/mg protein). Statistical analysis showed that TFF1 levels were significantly higher in premenopausal patients (p = 0.001), as well as in tumors showing any of the following characteristics: good differentiation (p = 0.0001), ER and PgR positivity (p = 0.0001 and p = 0.001, respectively), diploidy (p = 0.045) and a high S-phase fraction (p = 0.001). In addition, the presence of high intratumoral TFF1 levels (cut-off: 2 ng/mg protein) was independently associated with a shorter overall survival in the group of patients as a whole (p = 0.001) as well as in the subgroup with node-negative breast cancer (p = 0.0004). Likewise, high intratumoral TFF1 levels were associated with a more prolonged overall survival in patients who received adjuvant tamoxifen (p = 0.004). CONCLUSIONS: In breast cancer patients, intratumoral TFF1 levels are associated with a better clinical outcome, especially in those with node-negative tumors. In addition, TFF1 levels have a low but significant predictive value in regards to response to adjuvant therapy with tamoxifen.

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.

A new area multidetector dosemeter for mixed n-gamma fields.

A new instrument to assess neutron ambient doses has been designed and constructed. In its design, spectrometric capabilities have been implemented that allow to take into account the energy spectrum of the neutron field in the evaluation of the operational magnitude, ambient dose equivalent, H*(10). This dosemeter is based on the moderation-absorption technique and can be employed over a wide range of energies from thermal to 20 MeV. It consists of a spherical shaped polyethylene moderator with a set of thermoluminescence dosemeters (TLDs) inserted in different positions of its interior to evaluate the external neutron energy spectrum. At this moment the system uses pairs 6LiF:Mg,Ti (TLD-600) and 7LiF:Mg,Ti (TLD-700) thermoluminescence dosemeters for a better gamma discrimination. The dosemeter response matrix was calculated using the MCNP4C Monte Carlo code (MC). The viability of the dosemeter for area dosemetry has been examined experimentally showing its capabilities over a wide range of energies.

Significance of cytosolic hyaluronan levels in gastric cancer.

BACKGROUND: Hyaluronan a high-molecular weight glycosaminoglycan, is considered to be involved in the growth and progression of malignant tumours. The objective of this work was to evaluate the cytosolic hyaluronan content in gastric cancer cells, its possible relationship with clinicopathological tumour parameters and its potential prognostic significance. METHODS: Cytosolic hyaluronan levels were examined utilizing immunoenzymatic techniques in 129 patients with gastric cancer. The mean follow-up period for these patients was 28 months. RESULTS: Cytosolic hyaluronan levels ranged widely in tumours as well as in adjacent mucosal samples (median (range) 2822 (50-24,523) versus 3650 (507-20,782) ng/mg protein). Statistical analysis showed that tumour hyaluronan levels correlated significantly with patient's sex and the presence of lymphatic invasion. In addition, high tumour hyaluronan levels were significantly associated with shorter overall survival period (p<0.05). CONCLUSIONS: Our results suggest that high tumoral cytosolic hyaluronan levels are associated with lesions of unfavorable outcome in gastric cancer patients. Thus, hyaluronan may provide additional prognostic information to that given by other biochemical markers currently used in gastric cancer.

Membranous levels of c-erbB-2 oncoprotein in gastric cancer: their relationship with clinicopathological parameters and their prognostic significance.

BACKGROUND: The protein encoded by the c-erbB-2 gene is a membrane receptor expressed in a variety of solid human cancers and directly related to poor prognosis. The objective of this work was to evaluate the clinical value of the quantification of membranous oncoprotein levels in gastric cancer. MATERIALS AND METHODS: Membranous c-erbB-2 levels were examined by means of a sandwich immunoenzymatic assay in 82 patients with gastric cancer. The median follow-up period for these patients was 16 months. In addition, c-erbB-2 expression was analyzed by immunohistochemistry in 57 gastric carcinomas. RESULTS: Membranous c-erbB-2 levels ranged widely in the studied tumors (44-112,000 NHU/mg protein). Median c-erbB2 content was significantly higher in intestinal-type tumors than in diffuse-type tumors (p = 0.01). In addition, high levels of c-erbB-2 were significantly associated with shorter relapse-free survival and overall survival in patients with resectable gastric carcinomas (p = 0.01 and p = 0.04, respectively). However, the correlation between immunohistochemistry and ELISA determinations did not reach statistical significance. CONCLUSION: Our results suggest a potential prognostic value of membranous c-erbB-2 quantification by immunoenzymatic assay in gastric cancer. However, its possible role in the selection of patients with a view to the possible introduction of Herceptin as a novel drug against gastric cancer is at present uncertain.

Epidermal growth factor receptor and c-erbB-2 contents in unresectable (UICC R1 or R2) gastric cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) and c-erbB-2 are membrane receptors expressed in a variety of solid human cancers and directly correlated with poor prognosis. The objective of this work was to evaluate the EGFR and c-erbB-2 levels in non-resectable gastric carcinomas, their possible relationship with a variety of clinicopathological tumor parameters, and their prognostic significance. METHODS: This was a prospective analysis of 65 patients with unresectable gastric carcinomas (UICC R1 or R2), who underwent palliative surgery and were followed up for a median period of 13 months. Membranous EGFR levels were examined by radioligand binding assays and cytosolic c-erbB-2 levels by means of an immunoenzymatic assay. RESULTS: There was a wide variability in EGFR (80.3-2910 fmol/mg of protein) and c-erbB-2 (0.4-10071 NHU/mg of protein) levels in neoplastic tissues from patients with unresectable gastric carcinomas. Median c-erbB2 was significantly higher in tumors of the intestinal type than in tumors of the diffuse type (p = 0.035) and in R2 than in R1 tumors (p = 0.016). Statistical analysis showed that there was no relationship between tumor c-erbB-2 or EGFR content and any other patient or tumor characteristics. However, high levels of EGFR were significantly associated with a shorter overall survival (p = 0.01). CONCLUSION: Our data suggest a role of both transmembrane proteins in the progression of gastric cancer. EGFR and c-erbB-2 contents in unresectable gastric cancer could be utilized as appropriate biological markers for selecting candidates for treatment based on EGFR and/or c-erbB-2 inhibition.

Clinical significance of the epidermal growth factor receptor and HER2 receptor in resectable gastric cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR or HER1) and its homolog c-erbB-2 (HER2) are membrane receptors. Both EGFR and HER2 genes are overexpressed in a variety of solid human cancers and are related to poor prognosis of the patients. The objective of this work was to evaluate the EGFR and HER2 contents in resectable gastric cancer, their possible relationship with clinicopathologic parameters of tumors, and their prognostic significance. METHODS: This was a prospective analysis of 63 patients with resectable gastric carcinomas, with a mean follow-up period of 40.7 months. Membranous EGFR levels were examined by radioligand binding assays, and cytosolic HER2 levels were examined by means of an immunoenzymatic assay. RESULTS: There was a wide variability of EGFR (1-1,239 fmol/mg of protein) and HER2 (7-20,863 NHU/mg of protein) levels in tumors. There was no significant correlation between these levels and patient or tumor characteristics. However, high levels of EGFR and HER2 were significantly associated with a shorter overall survival period (P =.03 and P =.02, respectively). CONCLUSIONS: There is a wide variability in membranous EGFR levels and in cytosolic HER2 levels in gastric cancer, which seems to be related to the biological heterogeneity of these tumors. In addition, high tumor EGFR and HER2 levels were associated with an unfavorable outcome in patients with resectable gastric cancer.

Cytosolic levels of an estrogen-induced breast cancer-associated peptide (TFF1/pS2) in colorectal cancer: clinical significance and relationship with steroid receptors.

BACKGROUND: The Trefoil Factor 1 (TFF1/pS2), a peptide consisting of 60 amino acids, is the most abundant estrogen-induced messenger RNA in MCF-7 breast cancer cells and is also expressed by colorectal carcinomas. The objective of this work was to evaluate the cytosolic TFF1 content in colorectal carcinomas, its possible relationship with estrogen and progesterone receptors as well as with clinicopathological tumor parameters, and its potential prognostic significance. METHODS: Cytosolic TFF1 levels were examined by immunoradiometric assay in 178 patients with resectable colorectal cancer. The mean follow-up period was 32 months. RESULTS: There was a wide variability of cytosolic TFF1 levels in tumor-surrounding mucosa samples (0.09-42.5 ng/mg protein) as well as in tumors (0.01-270 ng/mg protein). Comparison of paired mucosa and carcinoma samples showed significantly higher TFF1 levels in tumors (mean: 17.1 ng/mg protein) than in mucosa samples (10 ng/mg protein) (p = 0.027). TFF1 levels were significantly higher in mucosa samples surrounding distal colon and rectal tumors (p = 0.0001) and in tumor samples obtained from older patients (p = 0.007). However, there were no significant differences in tumor TFF1 levels with respect to clinicopathological parameters such as the patient's sex, tumor location, stage, histological grade, ploidy, S-phase, or tumor estrogen and progesterone receptors. In addition, there was no significant relationship between tumor TFF1 levels and disease outcome. CONCLUSIONS: TFF1 may play an as yet undetermined role in the tumorigenesis of colorectal carcinomas. However, cytosolic levels of TFF1 do not seem to have any prognostic significance in colorectal carcinomas.

Prognostic significance of tissue-type plasminogen activator (tPA) content in gastric cancer and surrounding mucosa.

AIMS: We analyzed the tPA content in primary gastric carcinomas and surrounding mucosa in order to assess the relationship between tPA content, clinicopathological tumor characteristics, and estrogen and progesterone receptor content. We evaluated the prognostic value of this serine protease in gastric cancer patients. PATIENTS AND METHODS: 122 resected gastric neoplasms and 95 adjacent mucosa samples were studied. The tPA content was measured in cytosol by an ELISA method. Cytosolic ER and PgR were measured with a solid phase enzyme immunoassay. RESULTS: Cytosolic tPA levels in neoplastic tissues (median 1.0 ng/mg prot) were significantly lower (p=0.002) than those found in paired mucosa samples (median 2.3 ng/mg prot). There was no significant association between tPA levels and clinicopathological parameters or PgR content, but tPA levels were significantly correlated with ER content. The intermediate-tPA-content group, corresponding to samples with between 0.3 and 1.70 ng/mg protein, proved to have a significantly high risk of relapse. CONCLUSIONS: We found a wide variability in tPA levels in gastric carcinoma and adjacent mucosa samples, with significantly decreased levels in tumors and a significantly positive relationship between tPA levels and ER status. There was a non-monotonic relationship between tPA levels and prognosis in patients with gastric cancer.

The use of passive environmental TLDs in the operation of the Spanish early warning network 'REVIRA'.

As required by different international agreements, the regulatory body in Spain (Consejo de Seguridad Nuclear) implemented in 1992 a national automatic network (REVIRA) that continuously monitors radiation levels in order to give early warning of incidents having potential transboundary implications. The detector for environmental gamma-radiation dose rate is an active instrument based on a Geiger-Müller counter. However, the use of passive environmental dosemeters provides an additional low-cost dose estimate with an independent centralised calibration and even better basic features than active instruments. Since 1999, all 25 REVIRA stations have been monitored with passive TL environmental dosemeters based on LiF:Mg,Cu,P and operated according to the procedures established at Ciemat. This paper presents the obtained results and the further analysis considering differences in aspects such as photon energy response, inherent background or response to cosmic rays. The benefits of the use of passive environmental dosemeters in early warning networks are discussed.

Experience gained from the Ciemat External Dosimetry Service participation in several environmental dosimetry intercomparisons.

This paper summarises the experience gained by the Ciemat External Dosimetry Service (EDS) in the environmental dosimetry intercomparisons organised by the US Department of Energy. During the three latest intercomparisons. important dosimetry aspects such as energy calibration, energy response, dosimetric quantities and signal stability have been tested by the Ciemat EDS on up to seven different thermoluminescent (TL) materials, including hypersensitive phosphors, and employing several dosimetric systems. In last year's intercomparison, in addition to TL dosemeters the Ciemat EDS sent a set of silicon diode active dosemeters, usually used as personal dosemeters, to be tested in environmental conditions without intervention for more than 3 months. All the results obtained from different dosemeters have undergone an exhaustive analysis process in order to find some conclusions that may help to increase the knowledge of field performance of these devices in real but controlled environmental conditions.

Evaluation of the peripheral dose to uterus in breast carcinoma radiotherapy.

The absorbed dose outside of the direct fields of radiotherapy treatment (or peripheral dose, PD) is responsible for radiation exposure of the fetus in pregnant women. Because the radiological protection of the unborn child is of particular concern in the early period of the pregnancy, the aim of this study is to estimate the PD in order to assess the absorbed dose in the uterus in a pregnant patient irradiated for breast carcinoma therapy. The treatment was simulated on an Alderson-Rando anthropomorphic phantom, and the radiation dose to the fetus was measured using an ionisation chamber and thermoluminescence dosemeters. Two similar treatments plans with and without wedges were delivered, using a 6 MV photon beam with two isocentric opposite tangential fields with a total dose of 50 Gy, in accordance with common established procedures. Average field parameters for more than 300 patients were studied. Measurements showed the fetal dose to be slightly lower than 50 mGy, a level at which the risk to the fetus is uncertain, although several authors consider this value as the dose threshold for deterministic effects. The planning system (PS) underestimated PD values and no significant influence was found with the use of wedge filters.

Importancia de la edad como factor pronóstico determinante de la variabilidad de las características clínico-patológicas de las pacientes con cáncer de mama / Importance of the age as factor determining prognosis of the variability of the clinical-pathological characteristics of patients with breast cancer

Objetivo: analizar la importancia de la edad como factor pronóstico en el cáncer de mama, lo cual podría tener importantes implicaciones en el tratamiento y manejo clínico de las pacientes. Material y métodos: estudio retrospectivo de 769 pacientes intervenidas quirúrgicamente por cáncer de mama (1983-1999). El tiempo medio de seguimiento fue de 34,4 meses. Se realizaron estudios bioquímicos para la determinación de receptores de estrógenos y progesterona, contenido de ADN y fase S. Resultados: la edad media de las 769 pacientes fue de 59 años, y la década de mayor presentación del cáncer de mama fue la de los 50 años (26,5 per cent). Encontramos una asociación estadísticamente significativa entre la edad de las pacientes y el tamaño tumoral (p<0,0001), grado histológico (p<0,018), contenido de receptores de estrógenos (p<0,014) y fase S (p<0,019). Las pacientes de menor edad tuvieron un mayor número de casos de tumores de menor ta maño, histológicamente menos diferenciados y con receptores estrogénicos negativos. El análisis univariante demostró que el mayor tamaño tumoral, el estadio nodal positivo y el grado histológico indiferenciado de los tumores estuvieron significativa y positivamente asociados con un menor tiempo libre de enfermedad y supervivencia total de las pacientes. Sin embargo, no existieron diferencias significativas en el pronóstico entre los diferentes grupos de pacientes clasificadas en función de sus distintas edades. Conclusiones: el presente estudio demuestra diferencias en las características clínicas, morfológicas y biológicas de los carcinomas mamarios en función de la edad de las pacientes. Sin embargo , nuestros resultados no demostraron diferencias significativas en el pronóstico de las pacientes en función de su edad. Ello podría tener importantes implicaciones de cara al tratamiento y manejo clínico de las pacientes, principalmente de aquellas de más avanzada edad (AU)

Clinical significance of epidermal growth factor receptor content in gastric cancer.

The objective of this work was to evaluate the epidermal growth factor receptor (EGFR) content in gastric cancer, its possible relationship with clinicopathological parameters of tumors and its prognostic significance. Membranous EGFR levels were examined by radioligand binding assays in 110 patients with gastric cancer. The mean follow-up period was 30.7 months. EGFR levels of tumors ranged widely, from 0.3 to 510 fmol/mg protein. EGFR levels were significantly higher (p<0.0005) in neoplastic tissue than in paired adjacent mucosa samples (median) (n= 84; 8.7 vs. 3.9 fmol/mg protein). Intratumoral EGFR levels were significantly correlated with tumor stage (p<0.05), and were higher in patients with stage III tumors (median) (7.6, 6.4, 12.3 and 7.5 fmol/mg protein for stages I, II, III and IV, respectively). In addition, the tumor/mucosa ratios of the EGFR content were significantly higher (p<0.05) in patients with stage III tumors (1, 1.8, 3.9, and 0.92, respectively). Although there was no significant relationship between EGFR levels of tumors and overall survival, the results suggest a role for EGFR in tumor progression of gastric cancer.