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African swine fever (ASF) is a devastating disease with a high impact on the pork industry worldwide. ASF virus (ASFV) is a very complex pathogen, the sole member of the family Asfaviridae , which induces a state of immune suppression in the host through infection of myeloid cells and apoptosis of lymphocytes. Moreover, haemorrhages are the other main pathogenic effect of ASFV infection in pigs, related to the infection of endothelial cells, as well as the activation and structural changes of this cell population by proinflammatory cytokine upregulation within bystander monocytes and macrophages. There are still many gaps in the knowledge of the role of proteins produced by the ASFV, which is related to the difficulty in producing a safe and effective vaccine to combat the disease, although few candidates have been approved for use in Southeast Asia in the past couple of years.

Objectives: To assess of the clinical performance of Proclarix ® (a novel Conformité Européenne [CE]-marked biomarker test aiding in the identification of clinically significant prostate cancer [csPCa]) alone or in combination with multiparametric magnetic resonance imaging (mpMRI) to predict csPCa (International Society of Urological Pathology Grade Group ≥2)., Patients and Methods: The study included blood samples from 721 men undergoing mpMRI followed by biopsy at University College London, London, and Vall d'Hebron University Hospital, Barcelona. Samples were tested blindly. The Proclarix-MRI model combining prostate volume, Proclarix and mpMRI results was trained using the UCL cohort (n = 159) and validated in the Vall d'Hebron cohort (n = 562). Its diagnostic performance was established in correlation to biopsy outcome and compared to available clinical parameters and risk calculators., Results: Clinical performance of the Proclarix-MRI model in the validation cohort did not significantly differ from the training cohort and resulted in a sensitivity for csPCa of 90%, 90% negative predictive value and 66% positive predictive value. The Proclarix-MRI score's specificity (68%) was significantly (P < 0.001) better than the MRI-European Randomized study of Screening for Prostate Cancer risk score (51%), Proclarix (27%) or mpMRI (28%) alone. In addition, Proclarix by itself was found to be useful in the MRI Prostate Imaging-Reporting and Data System (PI-RADS) score 3 subgroup by outperforming prostate-specific antigen density in terms of specificity (25% vs 13%, P = 0.004) at 100% sensitivity., Conclusion: When combined with mpMRI and prostate volume, Proclarix reliably predicted csPCa and ruled out men with no or indolent cancer. A large reduction of two thirds of unneeded biopsies was achieved. Proclarix can further be used with high confidence to reliably detect csPCa in men with an indeterminate PI-RADS score 3 mpMRI. Despite these encouraging results, further validation is needed., (© 2023 BJU International.)

Nipah virus (NiV) is an emerging pathogen that can cause severe respiratory illness and encephalitis in humans. The main reservoir is fruit bats, distributed across a large geographical area that includes Australia, Southeast Asia, and Africa. Incursion into humans is widely reported through exposure of infected pigs, ingestion of contaminated food, or through contact with an infected person. With no approved treatments or vaccines, NiV poses a threat to human public health and has epidemic potential. To aid with the assessment of emerging interventions being developed, an expansion of preclinical testing capability is required. Given variations in the model parameters observed in different sites during establishment, optimisation of challenge routes and doses is required. Upon evaluating the hamster model, an intranasal route of challenge was compared with intraperitoneal delivery, demonstrating a more rapid dissemination to wider tissues in the latter. A dose effect was observed between those causing respiratory illness and those resulting in neurological disease. The data demonstrate the successful establishment of the hamster model of NiV disease for subsequent use in the evaluation of vaccines and antivirals.

Demineralization is a process of loss of minerals in the dental hard tissue that affects seriously the health of the patients, as it diminishes the tooth resistance, generating chewing problems by altering the occlusal structure, hypersensitivity, and pulpal problems. Demineralization can be produced by pathological processes as erosion or caries, or by surgical processes as etching. Due to the complexity of natural demineralization processes, it is mandatory to provide quantitative and standardized tests to allow their study in controlled laboratory conditions. Ultrasonic techniques are suitable for this purpose as they are nondestructive, quick, and provide localized mechanical information about the tissue, which is related with its degree of demineralization. In the present work, we evaluate the complete process of demineralization of the human dentin under controlled laboratory conditions using a pulse-echo ultrasonic technique. Up to 15 human dentin teeth have been demineralized with phosphoric acid at 10%. The time-of-flight measurements using the pulse-echo system allows to obtain the speed of sound in healthy (3415 m/s) and demineralized dentin tissue (1710 m/s), as well as to characterize the dynamical process of the acid penetration, which generates well-defined boundaries between two media (demineralized and mineralized dentin), showing very different mechanical properties. These boundaries advance in depth at an initial rate of [Formula: see text]/min, decelerating at -9.3 nm/min 2 until the whole demineralization of the sample is achieved. In addition, the technique allows to measure the relevance of the demineralization produced by the acid residues inside the tooth once it has been removed from the acidic solution. Beyond the assessment of artificial demineralization lesions under laboratory conditions, as demonstrated in this article, the proposed technique opens new approaches to the assessment of demineralization caused by natural caries in vivo.

No consensus currently exist on the optimal treatment of patients with high-risk nonmuscle invasive (HGT1) micropapillary variant of bladder cancer (MPBC). Transcripsome analysis may allow stratification of MPBC-HGT1 enabling prediction of recurrence and guide therapeutic management for individual patients. Whole transcriptome RNA-Sequencing of tumors from 23 patients with MPBC-HGT1 and 64 conventional urothelial carcinomas (cUC) (reference set) was performed. Differentially expressed genes between MPBC-HGT1 and cUC-HGT1 were explored. Cox proportional hazard models and Kapplan-Meier methods were used to assess the relation between time to progression (TTP) and individual gene expression adjusting for clinical covariates. Over 3000 genes were differentially expressed in MPBC-HGT1 as compared with cUC-HGT1 and a 26-gene signature is characteristic of MPBC within HGT1. A set of three genes; CD36, FAPB3 and RAETE1; were significantly associated with TTP. High expression of FABP3 and CD36 were associated with shorter TTP (p = 0.045 and p = 0.08) as was low expression of RAET1E (p = 0.01). Our study suggest that a 26-gene signature can define MPBC-HGT1 within conventional urothelial carcinomas. A prognostic risk index of three genes (FABP3, CD36 and RAET1E) was found to be associated with shorter TTP and may help classify a group of patients with MPBC-HGT1 with high-risk of early progression. These observations might have implications in terms of radical cystectomy recommendation in MPBC patients.

This corrects the article DOI: 10.1038/nature22964.

Activation of the PTEN-PI3K-mTORC1 pathway consolidates metabolic programs that sustain cancer cell growth and proliferation. Here we show that mechanistic target of rapamycin complex 1 (mTORC1) regulates polyamine dynamics, a metabolic route that is essential for oncogenicity. By using integrative metabolomics in a mouse model and human biopsies of prostate cancer, we identify alterations in tumours affecting the production of decarboxylated S-adenosylmethionine (dcSAM) and polyamine synthesis. Mechanistically, this metabolic rewiring stems from mTORC1-dependent regulation of S-adenosylmethionine decarboxylase 1 (AMD1) stability. This novel molecular regulation is validated in mouse and human cancer specimens. AMD1 is upregulated in human prostate cancer with activated mTORC1. Conversely, samples from a clinical trial with the mTORC1 inhibitor everolimus exhibit a predominant decrease in AMD1 immunoreactivity that is associated with a decrease in proliferation, in line with the requirement of dcSAM production for oncogenicity. These findings provide fundamental information about the complex regulatory landscape controlled by mTORC1 to integrate and translate growth signals into an oncogenic metabolic program.

There is a lack of studies on somatic gene mutations and cell signaling driving penile carcinogenesis. Our objective was to analyze somatic mutations in genes downstream of EGFR in penile squamous cell carcinomas, especially the mTOR and RAS/MAPK pathways. We retrospectively analyzed somatic mutations in 10 in situ and 65 invasive penile squamous cell carcinomas by using Sequenom's Mass Spectrometry iPlex Technology and Oncocarta v1.0 Panel. The DNA was extracted from FFPE blocks and we identified somatic missense mutations in three in situ tumors and in 19 invasive tumors, mostly in PIK3CA, KRAS, HRAS, NRAS, and PDGFA genes. Somatic mutations in the PIK3CA gene or RAS family genes were neither associated with tumor grade, stage or outcome, and were equally often identified in hrHPV positive and in hrHPV negative tumors that showed no p53 expression. Mutations in PIK3CA, KRAS, and HRAS are frequent in penile squamous cell carcinoma and likely play a role in the development of p53-negative tumors. Although the presence of these mutations does not seem to correlate with tumoral behavior or outcome, they could be biomarkers of treatment failure with anti-EGFR mAb in patients with penile squamous cell carcinoma., (© 2015 Wiley Periodicals, Inc.)

Purpose: Penile squamous cell carcinoma is a rare neoplasm associated with a high risk of metastasis and morbidity. There are limited data on the role of the mTOR signaling pathway in penile squamous cell carcinoma carcinogenesis and tumor maintenance. We assessed a possible role for mTOR signaling pathway activation as a potential predictive biomarker of outcome and a therapeutic target for penile cancer., Material and Methods: A cohort of 67 patients diagnosed with invasive penile squamous cell carcinoma from 1987 to 2010 who had known HPV status were selected for study. Tissue microarrays were constructed with 67 primary penile squamous cell carcinomas, matched normal tissues and 8 lymph node metastases. Immunohistochemical staining was performed for p53, pmTOR, pERK, p4E-BP1, eIF4E and peIF4E. Expression was evaluated using a semiquantitative H-score on a scale of 0 to 300., Results: Expression of pmTOR, p4E-BP1, eIF4E and peIF4E was increased in penile tumors compared with matched adjacent normal tissues, indicating activation of the mTOR signaling pathway in penile tumorigenesis. Over expression of pmTOR, peIF4E and p53 was significantly associated with lymph node disease. peIF4E and p53 also correlated with a poor outcome, including recurrence, metastasis or disease specific death. In contrast, pERK and p4E-BP1 were associated with lower pT stages. pmTOR and intense p53 expression was associated with HPV negative tumors., Conclusions: Activation of mTOR signaling may contribute to penile squamous cell carcinoma progression and aggressive behavior. Targeting mTOR or its downstream signaling targets, such as peIF4E, may be a valid therapeutic strategy., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Type 2 diabetes has been associated with decreased risk of prostate cancer in observational studies, and this inverse association has been recently confirmed in several large cohort studies. However the mechanisms involved in this protective effect remain to be elucidated. The aim of the present study was to explore whether different features of type 2 diabetes (hyperinsulinemia, hyperglycemia and tumor necrosis factor alpha [TNF-α]) protect against the development of prostate cancer. For this purpose LNCaP cells were used for in vitro experiments and nude mice in which PAC120 (hormone-dependent human prostate cancer) xenografts had been implanted were used for in vivo examinations. We provide evidence that increasing glucose concentrations downregulate androgen receptor (AR) mRNA and protein levels through NF-κB activation in LNCaP cells. Moreover, there was a synergic effect of glucose and TNFα in downregulating the AR in LNCaP cells. By contrast, insulin had no effect on AR regulation. In vivo experiments showed that streptozotocin-induced diabetes (STZ-DM) produces tumor growth retardation and a significant reduction in AR expression in PAC120 prostate cancer mice. In conclusion, our results suggest that hyperglycemia and TNF-α play an important role in protecting against prostate cancer by reducing androgen receptor levels via NF-κB.

Objective: Recently, the authors demonstrated altered gene expression in the jejunal mucosa of diarrhoea-predominant irritable bowel syndrome patients (IBS-D); specifically, the authors showed that genes related to mast cells and the intercellular apical junction complex (AJC) were expressed differently than in healthy subjects. The aim of the authors here was to determine whether these alterations are associated with structural abnormalities in AJC and their relationship with mast cell activation and IBS-D clinical manifestations., Design: A clinical assessment and a jejunal biopsy were obtained in IBS-D patients (n=45) and healthy subjects (n=30). Mucosal mast cell number and activation were determined by quantifying CD117(+) cells/hpf and tryptase expression, respectively. Expression and distribution of AJC specific proteins were evaluated by western blot and confocal microscopy. AJC ultrastructure was assessed by transmission electron microscopy., Results: Compared with healthy subjects, IBS-D patients exhibited: (a) increased mast cell counts and activation; (b) increased protein expression of claudin-2, reduced occludin phosphorylation and enhanced redistribution from the membrane to the cytoplasm; and (c) increased myosin kinase expression, reduced myosin phosphatase and, consequently, enhanced phosphorylation of myosin. These molecular alterations were associated with ultrastructural abnormalities at the AJC, specifically, perijunctional cytoskeleton condensation and enlarged apical intercellular distance. Moreover, AJC structural alterations positively correlated both with mast cell activation and clinical symptoms., Conclusion: The jejunal mucosa of IBS-D patients displays disrupted apical junctional complex integrity associated with mast cell activation and clinical manifestations. These results provide evidence for the organic nature of IBS-D, a heretofore model disease of functional gastrointestinal disorders.

Background: Penile squamous cell carcinoma (PSCC) is a tumor with a high metastatic potential. In PSCC the attributable fraction to human papillomavirus (HPV) is not well established., Objective: We sought to provide novel data about the prevalence of HPV in a large series of penile intraepithelial neoplasia (PeIN) and invasive PSCC, correlating the results with the histologic subtype, p16(INK4a) immunostaining, and prognosis., Methods: A total of 82 PSCC were included in the study, 69 invasive and 13 PeIN. HPV detection was performed by polymerase chain reaction with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridization line probe assay. P16(INK4a) immunohistochemical expression on tissue microarrays was also analyzed., Results: HPV DNA was identified in 31 of 77 (40.2%) PSCC (22 of 67 invasive and 9 of 10 PeIN). In 25 of 31 (80.6%) cases HPV-16 was identified. HPV detection was significantly associated with some histologic subtypes: most basaloid and warty tumors were high-risk HPV (hrHPV) positive, whereas only 15% of usual PSCC were hr-HPV positive. All hrHPV-positive PSCC had an adjacent undifferentiated PeIN. Strong p16(INK4a) immunostaining correlated with hrHPV infection. Most undifferentiated PeIN showed p16(INK4a) immunohistochemical overexpression. Both hrHPV-positive and p16(INK4a)-positive tumors showed a better overall survival without reaching statistical significance., Limitations: This was a retrospective study., Conclusions: Our results suggest that most hrHPV-positive PSCC develop from undifferentiated hrHPV-positive PeIN. P16(INK4a) immunostaining may be useful in identifying both etiologically related hrHPV-positive tumors and those with better outcome. The routine use of p16(INK4a) staining should be incorporated in histologic evaluation of PSCC., (Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Objectives: To evaluate the clinical and pathologic features and the prognostic relevance of unclassified RCC with -TFE3 over-expression in our adult series. Recent studies suggest that renal cell carcinomas (RCCs) associated with the newly recognized Xp11.2 translocation (transcription factor E3 [TFE3] gene fusions) can be found among adults with RCC showing a very aggressive disease-course., Material and Methods: We evaluated tumour specimens from 25 patients with unclassified RCC morphology out of 298 RCCs in the last 12 years in a tertiary academic centre. Immunohistochemistry was performed using monoclonal antibody for TFE3 C-terminal section, taking nuclear label into consideration. RT-PCR technique was performed for ASPL-TFE3 gene fusion on two tumours with available frozen tissue., Results: Of the 25 cases analyzed, 8 (32%) showed positivity for TFE3 and 17 were negative for TFE3 staining. Two tumors with ASPL-TFE3 gene fusion also showed TFE3 over-expression. Fifty percent of the positive patients had lymph node metastatic disease, whereas only one TFE3-negative patient (5.8%) showed evidence of lymph node spread and cava thrombus at diagnosis. Of the TFE3-positive patients, three had a vena cava thrombus (37.5%). Seven of the eight positive cases (87.5%) were diagnosed with a high Fuhrman grade (III/IV). In comparison, five of 17 (29.4%) TFE3-negative patients had a high Fuhrman grade. Five of eight TFE3-positive patients relapsed rapidly at 3 month follow-up; conversely none of the negative cases relapsed. At 36-month mean follow-up, 5-year cancer-specific survival was 15.6% for TFE3-positive patients and 87.5% for TFE3-negative patients (P < 0.001)., Conclusion: Patients with unclassified RCC and TFE3 positivity have a grim prognosis due to their advanced stage at presentation and aggressive biologic features compared with the TFE3-negative unclassified RCC cases., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

In this report, we present the clinicopathologic features of 27 cases of the lipid cell variant of urothelial bladder carcinoma. This is a rare variant of bladder cancer recognized by the current WHO classification of urologic tumors. The lipid cell component varied from 10% to 50% of the tumor specimen; in 11 cases the lipid cell component composed greater than 30% of the tumor. The architectural pattern of the tumor varied from solid expansile to infiltrative nests. The large epithelial tumor cells had an eccentrically placed nucleus and abundant vacuolated cytoplasm resembling signetring lipoblasts. Mucin stains were negative in all the cases. Typical features of high grade conventional urothelial carcinoma were present in all the cases with micropapillary or plasmacytoid carcinoma in 2 and 1 cases, respectively; extensive squamous or glandular differentiation was present in 2 additional cases. Most neoplastic cells had nuclei of intermediate nuclear grade with occasional nuclear pleomorphism. Immunohistochemical staining showed that the lipid cell component was positive for cytokeratins 7, 20, CAM 5.2, high molecular weight (34ssE12) and AE1/AE3, epithelial membrane antigen, and thrombomodulin; vimentin and S100 protein were negative. The loss of heterozygosity (LOH) analysis was done on 8 cases using 4 polymorphic microsatellite markers (D9S171, D9S177, IFNA, and TP 53); LOH at least in 1 marker was present in 6 cases. The LOH results were the same for lipid variant and conventional urothelial carcinoma. Pathologic stage was Ta (n=1), T1 (=2), T2, at least (n=7), T3a (n=4), T3b (n=8), and T4a (n=5). Electron microcopy analysis based on 2 cases supported lipid content in tumor cells. Follow-up information was available in all the cases, ranging from 6 to 58 months (mean, 28 mo). Sixteen of the patients died of disease at 16 to 58 months (mean, 33 mo) and 8 patients were alive with disease at 8 to 25 months (mean, 22 mo). Another 3 patients died of other causes at 6 to 15 months (mean, 10 mo). In summary, lipid cell urothelial bladder carcinoma is typically associated with advanced stage high-grade urothelial carcinoma, in which the prognosis is poor and clonally related to the concurrent conventional urothelial carcinoma. In limited samples, it may be misdiagnosed as liposarcoma, sarcomatoid carcinoma (carcinosarcoma), or signetring cell carcinoma. Morphologic distinction from other malignant neoplasms with lipid cell phenotype is critical for its clinical management.

Purpose: The aim this study was to determine the pathologic complete response (pCR) rate defined as tumor regression grade 1 (TRG1) and toxicity profile of the combination of high-dose pre-operative radiotherapy and simultaneous UFT/leucovorin (LV) in patients with locally advanced rectal cancer., Materials/methods: Eligibility included biopsy proven rectal adenocarcinoma; T3-T4 N0-N2; performance status < 2 (ECOG) and adequate blood, hepatic and renal function. Treatment consisted of radiotherapy 54 Gy at 1.8 Gy/day and UFT 300 mg/m(2)/day and LV 60 mg/day, given simultaneously daily for 6 weeks. Surgery was performed within 4-6 weeks period after chemoradiotherapy. Patients who did not achieve TGR1 were to receive 4 cycles of adjuvant UFT/LV on days 1-28, every 5 weeks., Results: Sixty-eight patients were included. All but one received full dose of radiation and 62 had the total planned pre-operative UFT/LV dose. Grade 3 toxicities were diarrhea 7% and proctitis 3%. Complete resection was achieved in 62 patients (91%). Tumor regression grade 1 (TRG1) was seen in 11 patients (16%). Forty-eight patients received adjuvant UFT/LV. Grade 3 toxicity during adjuvant UFT/LV included diarrhea 12%, asthenia 4%, neutropenia 2%, and hand-foot syndrome 2%. The 3-year disease-free survival was 71%., Conclusions: Simultaneous high-dose pre-operative localized radiation therapy concurrent with UFT/LV is feasible and has a low toxicity profile. This schedule is highly effective and merits further investigation.

Objectives: To review the relationship between the Gleason grade and prostate volume in biopsy and radical prostatectomy (RP) specimens, and thus assess the hypothesis that smaller prostates have a greater incidence of high-grade tumours., Patients and Methods: We selected 390 patients who had RP at our institution, with a prostate-specific antigen (PSA) level of < 10 ng/mL and who had not had hormonal therapy. We retrospectively reviewed the data for transrectal ultrasonography (TRUS)-guided prostate biopsies from these patients and the RP specimens. Indications for biopsy included a PSA level of > or = 4 ng/mL or an abnormal digital rectal examination. High-grade tumours were defined as having a Gleason score of > or = 7., Results: The TRUS volume was statistically related to the rate of high-grade tumours at biopsy and RP. On multivariate analyses, TRUS volume was a significant predictor of high-grade tumour for biopsy and RP specimens, with an inverse relationship between high-grade tumours and prostate volume for biopsy and RP specimens., Conclusions: Our data suggest that there is a relationship between the rate of high-grade tumours and prostate volume even in biopsy and RP specimens and it is not an artefact related to the biopsy.

Celiac disease is usually associated with autoimmune disorders and has occasionally been reported in patients with inflammatory myopathies. Our aim was to determine the presence of celiac disease and antibodies associated with celiac disease in patients with inflammatory myopathies and to investigate their relationship. Serum antigliadin, anti-tissue transglutaminase, and antiendomysial antibodies were determined in 51 patients with inflammatory myopathies. HLA-DQ2 and -DQ8 alleles were studied to assess their complementary diagnostic value. Jejunal biopsy was performed in patients with moderate to high levels of antigliadin antibodies. Patients with jejunal histology consistent with celiac disease initiated a gluten-free diet. Seventeen patients (31%) were positive for antigliadin antibodies, which were significantly more frequent in patients with inclusion-body myositis than dermatomyositis (P < 0.001). Positive status to HLA-DQ2 and/or -DQ8 did not differ between antigliadin-positive (75% and 12.5%) or -negative (60% and 15%) patients. Three of five jejunal biopsies were diagnostic for celiac disease with histological normalization after a gluten-free diet. Thus, celiac disease is more prevalent in patients with inflammatory myopathies than in the general population. Positive status to HLA-DQ2 allele, which is known to be more frequent in patients with inflammatory myopathies, could explain the high prevalence of antigliadin antibodies in this population. The diagnostic value of HLA-DQ2 or -DQ8 haplotypes to detect celiac disease in patients with inflammatory myopathy is limited.

Purpose: To analyze the prognostic value of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in patients with locally advanced rectal cancer treated with preoperative radiotherapy., Methods: Eighty-one patients with locally advanced rectal cancer were studied. All patients received preoperative pelvic radiotherapy. Forty-seven patients received concomitant chemotherapy. Surgical resection was performed 4-8 weeks later in all patients. Immunohistochemical examination of COX-2 and VEGF was performed on the preirradiation diagnostic biopsies. An immunohistochemical score established from the extension and intensity of the markers was used for analysis. The log-rank test and proportional hazards regression analysis were used to calculate the probability that the biomarkers were associated with patient outcome., Results: COX-2 expression was positive in 38 tumors (51%) while VEGF expression was positive in 43 (57%). The only clinicopathological parameter significantly associated with COX-2 or VEGF expression was performance status. None of the 2 markers were found to predict treatment response. There was no statistically significant correlation between COX-2 and VEGF. Univariate analysis identified pathological stage (pT, pN) as prognostic for disease-free survival. When VEGF expression was analyzed, disease-free survival was reduced among patients with VEGF-positive tumors (p = 0.047). This was specifically related to metastases-free survival (p = 0.016). These results were not observed for COX-2. After multivariate analysis, the pT and pN stage remained as independent prognostic factors., Conclusions: VEGF-positive expression is an indicator of poor disease-free survival, specifically linked to distant metastasis. More aggressive treatment strategies are warranted in pT3-4 and pN1-2 rectal cancer patients., (Copyright 2006 S. Karger AG, Basel.)

Purpose: Epidermal growth factor receptor (EGFR) expression is observed in 50%-70% of colorectal carcinomas and is associated with poor prognosis. The aim of this study was to determine the EGFR expression rate in locally advanced rectal cancer and to analyze whether EGFR expression predicts tumor response to preoperative radiotherapy., Methods and Materials: Between December 1997 and October 2000, 45 patients were included. Treatment consisted of preoperative pelvic radiotherapy and, in 21 patients, 2 courses of 5-fluorouracil leucovorin. Surgical resection was performed 4-8 weeks later. Immunohistochemistry for EGFR was determined at the preradiation diagnostic biopsy and in the resected specimens. Immunostaining was performed using EGFR monoclonal antibody (Biogenex, MU 207-UC). Immunohistochemical staining was evaluated according to extension and intensity. We defined positive staining (EGFR+) as extension of 5% or more., Results: Preoperative treatment resulted in pathologic complete remission in 7 patients (15%), downstaging in 13 patients (29%), and no response in 25 patients (56%). EGFR+ was observed in 29 of 45 tumors (64%) and was associated with neither clinical tumor stage nor clinical nodal stage. The overall response rate was 34% in EGFR+ patients vs. 62% in those who were EGFR- (p = 0.07). Only 1 of the 7 pathologic complete remission patients was EGFR+ (p = 0.003)., Conclusions: EGFR is expressed in a significant number of locally advanced rectal tumors. EGFR expression is an indicator for poor response to preoperative radiotherapy in advanced rectal carcinoma.