A comparative study of the expression of cyclin D1, COX-2, and KI-67 in odontogenic keratocyst vs. ameloblastoma vs. orthokeratinized odontogenic cyst.

BACKGROUND: Odontogenic keratocysts (OKCs) and orthokeratinized odontogenic Cysts (OOCs) are distinct clinicopathological entities. OKC appears to behave in a way more similar to that of a neoplasm, such as ameloblastoma (AB). The aim of this study is to compare the influence of Ki-67, Cyclin D1 and COX-2 in the diagnosis and pathogenesis of OKC, OOC and AB. MATERIALS AND METHODS: A cross-sectional observational study of 41 samples was organized into 3 groups: (1) OKC n=22; (2) AB n=13 and (3) OOC n=6. Paraffin blocks were sectioned and stained with hematoxylin and eosin (H&E). Immunohistochemical study using Bond Polymer Refine Red Detection Kit, Leica, Wetzlar, Germany, was performed for the following antibodies: Ki-67, Cyclin D1 and COX-2. Double blind immunostaining was quantified subjectively. Staining: nuclear or cytoplasmic; nuclear (Ki-67 and Cyclin D1>5% positive) and cytoplasmic (COX-2; 1; 1-30 cytoplasm: 2; 31-60 cytoplasm; 3; 61-100 cytoplasm). Considering positive stained 61-100 cytoplasms. RESULTS: The expression of Ki-67 was higher in the OKC group than in the AB group (p<0.05). Cyclin D1 showed a higher expression in OKC vs. OOC and OKC vs. AB (p<0.05). Finally, expression of COX-2 was higher in OKC vs AB (p<0.05). CONCLUSIONS: COX-2, Ki-67 and Cyclin D1 show statistically significant differences between the groups, suggesting that they could be useful tools in the differential diagnosis between OKCs and OOC and a predictive indicator for their biologic behaviour. The higher expressions of these 3 markers of OKC vs AB highlight once more the aggressive behaviour of this now re-considered cystic lesion. These markers could prove useful in the choice of more aggressive surgical treatment in OKCs as their behaviour appears to be similar to that of a neoplasm.

A comparative study of the expression of cyclin D1, COX-2, and KI-67 in odontogenic keratocyst vs. ameloblastoma vs. orthokeratinized odontogenic cyst

Background: Odontogenic keratocysts (OKCs) and orthokeratinized odontogenic Cysts (OOCs) are distinct clinicopathological entities. OKC appears to behave in a way more similar to that of a neoplasm, such as ameloblastoma (AB). The aim of this study is to compare the influence of Ki-67, Cyclin D1 and COX-2 in the diagnosis and pathogenesis of OKC, OOC and AB. Materials and methods: A cross-sectional observational study of 41 samples was organized into 3 groups: (1) OKC n=22; (2) AB n=13 and (3) OOC n=6. Paraffin blocks were sectioned and stained with hematoxylin and eosin (H&E). Immunohistochemical study using Bond Polymer Refine Red Detection Kit, Leica, Wetzlar, Germany, was performed for the following antibodies: Ki-67, Cyclin D1 and COX-2. Double blind immunostaining was quantified subjectively. Staining: nuclear or cytoplasmic; nuclear (Ki-67 and Cyclin D1>5% positive) and cytoplasmic (COX-2; 1; 1–30 cytoplasm: 2; 31–60 cytoplasm; 3; 61–100 cytoplasm). Considering positive stained 61-100 cytoplasms. Results: The expression of Ki-67 was higher in the OKC group than in the AB group (p<0.05). Cyclin D1 showed a higher expression in OKC vs. OOC and OKC vs. AB (p<0.05). Finally, expression of COX-2 was higher in OKC vs AB (p<0.05). Conclusions: COX-2, Ki-67 and Cyclin D1 show statistically significant differences between the groups, suggesting that they could be useful tools in the differential diagnosis between OKCs and OOC and a predictive indicator for their biologic behaviour. The higher expressions of these 3 markers of OKC vs AB highlight once more the aggressive behaviour of this now re-considered cystic lesion. These markers could prove useful in the choice of more aggressive surgical treatment in OKCs as their behaviour appears to be similar to that of a neoplasm.(AU)

Antecedentes: Los queratoquistes odontogénicos (QQO) y los quistes odontogénicos ortoqueratinizantes (QOO) son entidades clínico-patológicas diferentes y el QQO parece estar más próximo al comportamiento de una neoplasia, como el ameloblastoma (AB). El objetivo de este estudio es comparar la influencia de Ki-67, ciclina D1, COX-2, en el diagnóstico y patogenia de QQO, QOO y AB. Materiales y métodos: Se ha diseñado un estudio observacional transversal con 41 muestras, en 3 grupos de estudio: (1) QQO: n=22, (2) AB n=13, y (3) QOO n=6. Se han seccionado bloques de parafina y teñido con hematoxilina y eosina y sometidas a una incubación con anticuerpos monoclonales (Kit Bond Polymer Refine Detection, Leica, Wezlar, Alemania) para la realización de un estudio inmunohistoquímico. Se ha cuantificado la inmunotinción, (nuclear o citoplasmática); nuclear (Ki-67 y ciclina D1; >5% positiva) y citoplasmática (COX-2; 1; 1-30 citoplasmas; 2; 31-60 citoplasmas; 3; 61-100 citoplasmas). Considerando positivo tinción a partir de 61-100 citoplasmas. Resultados: La expresión de Ki-67 ha sido mayor en el grupo del QQO con respecto a la de AB (p<0,05). Respecto a ciclina D1, mostró una expresión mayor en QQO vs. QOO (p<0,05); En el caso del marcador COX-2, la expresión ha sido mayor en QQO vs. AB (p<0,05). Conclusiones: La mayor expresión de estos 3 marcadores en QQO vs. AB resaltan una vez más el comportamiento agresivo de esta lesión ahora reconsiderada como «quística». Estos marcadores pueden ayudar a decidir tratamientos quirúrgicos más agresivos en las lesiones de QQO ya que parece comportarse como una «neoplasia».(AU)

Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR).

Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis due to its late diagnosis and strong chemoresistance to the current treatments. Therefore, finding new therapeutic targets is an urgent need nowadays. In this study, we report the role of the chromatin remodeler BPTF (Bromodomain PHD Finger Transcription Factor) as a therapeutic target in PDA. BPTF-silencing dramatically reduced cell proliferation and migration in vitro and in vivo in human and mouse PDA cell lines. Moreover, BPTF-silencing reduces the IC50 of gemcitabine in vitro and enhanced its therapeutic effect in vivo. Mechanistically, BPTF is required for c-MYC recruitment to the promoter of ABC-transporters and its downregulation facilitates gemcitabine accumulation in tumour cells, increases DNA damage, and a generates a strong synergistic effect in vivo. We show that BPTF is a therapeutic target in pancreatic ductal adenocarcinoma due to its strong effect on proliferation and in response to gemcitabine.

Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma.

Mitochondria are involved in the development and acquisition of a malignant phenotype in hematological cancers. Recently, their role in the pathogenesis of multiple myeloma (MM) has been suggested to be therapeutically explored. MYC is a master regulator of b-cell malignancies such as multiple myeloma, and its activation is known to deregulate mitochondrial function. We investigated the impact of mitochondrial activity on the distinct entities of the disease and tested the efficacy of the mitochondrial inhibitor, tigecycline, to overcome MM proliferation. COXII expression, COX activity, mitochondrial mass, and mitochondrial membrane potential demonstrated a progressive increase of mitochondrial features as the disease progresses. In vitro and in vivo therapeutic targeting using the mitochondrial inhibitor tigecycline showed promising efficacy and cytotoxicity in monotherapy and combination with the MM frontline treatment bortezomib. Overall, our findings demonstrate how mitochondrial activity emerges in MM transformation and disease progression and the efficacy of therapies targeting these novel vulnerabilities.

Craniopharyngiomas: A clinicopathological and molecular study of 52 cases - Experience in the Complejo Hospitalario de Toledo and Hospital Universitario 12 de Octubre (Madrid).

Craniopharyngiomas (CPs) are histologically benign tumors that are associated with high levels of morbidity. Two clinicopathological variants - adamantinomatous (ACP) and papillary (PCP) - have been described. They differ in their molecular features, whereby activating mutations in BRAF (V600E) and CTNNB1 genes characterize PCP and ACP, respectively. Recently, both variants have been shown to express elevated PD-L1 protein expression, but ACP also exhibited tumor cell-intrinsic PD-1 expression. In this study we analyze these molecular alterations in 52 cases with a long follow-up and examine their associations with immunohistochemical and clinical characteristics. ACPs comprise 73.1% of cases, while 21.2% are PCPs. Aberrant nuclear immunoreactivity for ß-catenin was observed in all ACPs. BRAF p.V600E mutations were observed in 90.9% of PCPs. Only one ACP case featured both alterations. Both types of CP exhibited strong nuclear staining for p63 with diffuse and basal distribution. ACP and PCP consistently expressed PD-L1, most in a substantial percentage of tumor cells, with a distinctive spatial distribution of expression in each subtype; only ACP demonstrated PD-1 expression. There was no evidence of differences in clinical prognosis between ACPs and PCPs. The identification of hallmark molecular signatures in the two CP variants is useful for sub-categorization in routine histopathology reporting. It is also pertinent to personalized therapy and for the development of improved non-invasive therapeutic strategies in this disease.

Oral pulse granuloma and oral pulse granuloma associated with odontogenic keratocyst: two clinical cases and a review of the literature / Granuloma oral pulse y granuloma oral pulse asociado a un queratoquiste odontogénico: 2 casos clínicos y revisión de la literatura

Two cases of oral pulse granuloma (OPG) or vegetable granuloma (VG) are presented, one of which was concomitant with an odontogenic keratocyst (OKC), which is an unusual finding. OKC is characterized by the presence of hyaline rings which include vessels, giant cells, other inflammatory cells and collagen fibres. There are two hypotheses as to its histogenesis: firstly, as a reaction to vegetable matter, such as legumes (thus the nomenclature "pulse" or edible seed) and secondly as a degenerative change in the vessel walls as a result of localized vasculitis. Due to the deceptive appearance of OPG, diagnosis can be challenging

En este artículo breve se presentan 2 casos de granuloma oral pulse (GOP) o granuloma vegetal, uno de ellos asociado a un queratoquiste odontogénico. Esta entidad está caracterizada por la presencia de estructuras hialinas en anillo que incluyen vasos, células gigantes, otras células inflamatorias y haces de fibras de colágeno. Sobre su origen todavía se barajan 2 hipótesis: una en la que se sospecha que se producen como reacción a estructuras vegetales como legumbres (de donde toma el nombre de «pulse» o semilla comestible de una leguminosa), y otra en la que se trataría de un cambio degenerativo de las paredes vasculares, resultado de una vasculitis localizada. Debido a la apariencia engañosa del GOP es fácil que a los patólogos les suponga un esfuerzo su diagnóstico. Se describe a continuación un hallazgo inusual de un GOP relacionado con un queratoquiste odontogénico

Oral pulse granuloma and oral pulse granuloma associated with odontogenic keratocyst: Two clinical cases and a review of the literature.

Two cases of oral pulse granuloma (OPG) or vegetable granuloma (VG) are presented, one of which was concomitant with an odontogenic keratocyst (OKC), which is an unusual finding. OKC is characterized by the presence of hyaline rings which include vessels, giant cells, other inflammatory cells and collagen fibres. There are two hypotheses as to its histogenesis: firstly, as a reaction to vegetable matter, such as legumes (thus the nomenclature "pulse" or edible seed) and secondly as a degenerative change in the vessel walls as a result of localized vasculitis. Due to the deceptive appearance of OPG, diagnosis can be challenging.

Retrospective study of 149 cases of salivary gland carcinoma in a Spanish hospital population

BACKGROUND: The clinical and histological characteristics of salivary gland tumors vary widely, complicating their diagnosis and management, and major differences have been recorded in the distribution of histopathological diagnoses among different countries. MATERIAL AND METHODS: This retrospective study reviewed the demographic (age, sex) and clinicopathological (pathology diagnosis and localization) characteristics of cases diagnosed with primary SGC between June 1992 and May 2014 in the Pathology Department of the 12 de Octubre Hospital of Madrid. Diagnoses were recorded according to the 2005 WHO classification. RESULTS: The study included 149 SCG patients, aged between 11 and 94 yrs., with mean age at onset of 55.56 yrs and peak incidence in the eighth decade of life. The male: female ratio was 1.01. The parotid gland was the most frequently involved (75.2%). The most frequent carcinoma was mucoepidermoid carcinoma (24.2%), followed by acinic cell carcinoma (15.4%). CONCLUSIONS: The demographic and histopathological characteristics of patients with salivary gland carcinomas in Spain, reported here for the first time, are broadly similar to those found in other countries

DEK oncogene is overexpressed during melanoma progression.

DEK is an oncoprotein involved in a variety of cellular functions, such as DNA repair, replication, and transcriptional control. DEK is preferentially expressed in actively proliferating and malignant cells, including melanoma cell lines in which DEK was previously demonstrated to play a critical role in proliferation and chemoresistance. Still, the impact of this protein in melanoma progression remains unclear. Thus, we performed a comprehensive analysis of DEK expression in different melanocytic tumors. The immunostaining results of 303 tumors demonstrated negligible DEK expression in benign lesions. Conversely, malignant lesions, particularly in metastatic cases, were largely positive for DEK expression, which was partially associated with genomic amplification. Importantly, DEK overexpression was correlated with histological features of aggressiveness in primary tumors and poor prognosis in melanoma patients. In conclusion, our study provides new insight into the involvement of DEK in melanoma progression, as well as proof of concept for its potential application as a marker and therapeutic target of melanoma.

Autoregulatory loop of nuclear corepressor 1 expression controls invasion, tumor growth, and metastasis.

Nuclear corepressor 1 (NCoR) associates with nuclear receptors and other transcription factors leading to transcriptional repression. We show here that NCoR depletion enhances cancer cell invasion and increases tumor growth and metastatic potential in nude mice. These changes are related to repressed transcription of genes associated with increased metastasis and poor prognosis in patients. Strikingly, transient NCoR silencing leads to heterochromatinization and stable silencing of the NCoR gene, suggesting that NCoR loss can be propagated, contributing to tumor progression even in the absence of NCoR gene mutations. Down-regulation of the thyroid hormone receptor ß1 (TRß) appears to be associated with cancer onset and progression. We found that expression of TRß increases NCoR levels and that this induction is essential in mediating inhibition of tumor growth and metastasis by this receptor. Moreover, NCoR is down-regulated in human hepatocarcinomas and in the more aggressive breast cancer tumors, and its expression correlates positively with that of TRß. These data provide a molecular basis for the anticancer actions of this corepressor and identify NCoR as a potential molecular target for development of novel cancer therapies.

Intra- and Inter-Tumoral Homogeneity of BRAF(V600E) Mutations in Melanoma Tumors.

The era of targeted therapy has introduced a new therapeutic perspective for melanoma patients. Treatment with BRAFV600 inhibitors has improved overall and disease-free survival in metastatic melanoma patients whose tumors harbor BRAFV600 mutations. Although the BRAFV600E mutation appears to have a critical role in tumor initiation, its expression during tumor progression remains controversial. In fact, various authors claim that BRAFV600E heterogeneity is evident in melanoma tumors. Herein, we investigated the pattern of BRAFV600E expression in matched primary and metastatic samples from 140 patients. Using a combination of real-time PCR and immunohistochemical analyses, we demonstrated that BRAFV600E expression is homogeneous in melanoma tumors and hypothesized that the heterogeneity described by others might be attributable to technical issues when molecular methods are used. We also demonstrated the high efficiency of the anti-BRAFV600E VE1 antibody for the detection of BRAFV600E mutations in melanoma tumors.

Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera.

JAK-STAT signaling through the JAK2V617F mutation is central to the pathogenesis of myeloproliferative neoplasms (MPN). However, other events could precede the JAK2 mutation. The aim of this study is to analyze the phenotypic divergence between polycytemia vera (PV) and essential thrombocytemia (ET) to find novel therapeutics targets by a proteomic and functional approach to identify alternative routes to JAK2 activation. Through 2D-DIGE and mass spectrometry of granulocyte protein from 20 MPN samples, showed differential expression of HSP70 in PV and ET besides other 60 proteins. Immunohistochemistry of 46 MPN bone marrow samples confirmed HSP70 expression. The median of positive granulocytes was 80% in PV (SD 35%) vs. 23% in ET (SD 34.25%). In an ex vivo model KNK437 was used as an inhibition model assay of HSP70, showed dose-dependent inhibition of cell growth and burst formation unit erythroid (BFU-E) in PV and ET, increased apoptosis in the erythroid lineage, and decreased pJAK2 signaling, as well as a specific siRNA for HSP70. These data suggest a key role for HSP70 in proliferation and survival of the erythroid lineage in PV, and may represent a potential therapeutic target in MPN, especially in PV.

Impact of epidermal growth factor receptor expression on disease-free survival and rate of pelvic relapse in patients with advanced cancer of the cervix treated with chemoradiotherapy.

OBJECTIVES: To determine the impact of the expression of epidermal growth factor receptor (EGFR) on disease-free survival (DFS) and on pelvic relapse in patients with advanced cancer of the cervix receiving concurrent chemoradiotherapy. METHODS: In 112 consecutive patients with advanced cancer of the cervix (11 stage IB2-IIA, 25 IIB, 63 IIIB, 13 IVA) treated with chemoradiotherapy between December 1994 and September 2004, the expression of EGFR using histoimmunochemistry was measured and used in univariate and multivariate analysis, along with variables such as age, International Federation of Gynecology and Obstetrics Staging System for Epithelial Ovarian Cancer (FIGO) stage, histology, Eastern Cooperative Oncology Group (ECOG), tumor size, and ganglia involvement diagnosed with computerized axial tomography, treatment with cisplatin to evaluate its impact on DFS and pelvic relapse. RESULTS: Of the 112 biopsies, 32 (28.6%) were negative or slightly positive (EGFR±) and 80 (71.4%) were moderate or intensely positive (EGFR++/+++). The overexpression of EGFR (++/+++) was significantly associated with an epidermoid histology (P < 0.0001), with a higher rate of pelvis relapse and a decreased DFS (hazard ratio [HR]: 2.31 [1.08-4.96]; P = 0.03). Overall, treatment with cisplatin increased DFS (HR: 0.51 [0.26-0.97]; P = 0.04). CONCLUSIONS: Patients with tumors of the cervix and overexpression of the EGFR++/+++ show a higher probability of pelvic relapses and a decreased disease-free survival. The poor prognosis of these tumors may be a consequence of an increase in radio-resistance.

Cisplatin-based radiochemotherapy improves the negative prognosis of c-erbB-2 overexpressing advanced cervical cancer.

OBJECTIVES: To determine the impact of c-erb-B2 overexpression on disease-free survival (DFS) and local relapse in patients with advanced cervical cancer (CC) receiving concurrent chemoradiotherapy treatment. METHODS: A total of 136 patients with advanced CC (FIGO stage: IB2-IIA [12]; IIB [34]; IIIB [71]; IVA [19]; including both epidermoid [86] and adenocarcinoma [14]) were analyzed to determine c-erb-B2 levels by immunohistochemistry (c-erb-B2 antibody; Dako, Glostrup, Denmark). Only c-erb-B2+++ biopsies were considered positive. All patients received pelvic radiotherapy, brachytherapy, and concurrent chemotherapy with 2 different regimens: 48 patients were treated with tegafur (800 mg/d orally) and 88 with tegafur (same doses) plus 5 cycles of weekly cisplatin 40 mg/m/wk intravenously. RESULTS: A total of 32 (23.5%) biopsies were considered c-erb-B2-positive. Three-year and 5-year DFS were 61% and 58% for c-erb-B2-negative patients and 36% and 36% for c-erB2-positive patients, respectively (P = 0.02). Patients were stratified in 4 groups according to their c-erb-B2 status and whether they received cisplatin. The group of patients with c-erb-B2 overexpression that did not receive platinum treatment had a higher rate of pelvic relapse (P < 0.0001), associated with a decreased DFS (P = 0.0014). CONCLUSIONS: c-erb-B2 overexpression may imply a poor prognosis for patients with advanced CC. Treatment with cisplatin-based radiochemotherapy improved outcome in these patients.

Prevención de la diabetes tipo 2 a través de un programa estandarizado de Educación para la Salud en Atención Primaria / Type 2 diabetes prevention through a standardised programme on Health Education in Primary Care

Dada la alta prevalencia de Diabetes Mellitus tipo 2 (DM2),se está llevando a cabo una investigación sobre la diabetes enEuropa y su prevención, mediante la intervención sobre estilosde vida modificables, conocido como “Estudio DE_PLAN”.Este trabajo forma parte de dicho estudio.Objetivo: evaluar la efectividad de un programa de intervenciónsobre cambios en los estilos de vida (dieta y ejercicio físico)para la prevención del desarrollo de DM2 en individuoscon alto riesgo.Material y método: estudio prospectivo longitudinal en poblaciónde 45 a 70 años, de ambos sexos, en la zona básica desalud de Arévalo. Se realizó un muestreo aleatorio por tarjetasanitaria, estratificado por zona: rural y semiurbana, calculándoseun tamaño muestral de 221 personas.El estudio se desarrolló en tres fases: Fase 1: cribado medianteescala de Findrisk, entrevista clínica, antropometría, analíticay PTOG. Tras la etapa de cribado, a las personas con Findrisk≥14 se les informa del programa de intervención Grupal; Fase2: intervención grupal: 4 talleres teórico-prácticos; y Fase 3:intervención continua. Refuerzo de la motivación y visitas clínicasanuales.Resultados: se excluyeron 21 por ser diabéticos. El Findriskfue ≤ 14 (alto riesgo) en 120 personas. Prevalencia de Diabetesdesconocida de 7,2%. De las 66 personas candidatas deambos sexos, aceptaron participar en el programa de intervención55 (83,3%) y lo terminaron 47. No hubo cambios significativosen el riesgo asociado al índice de masa corporal. Elporcentaje de inactividad inicial fue del 58%, del 11% después (..) (AU)

Given the high prevalence of type 2 Diabetes Mellitus (DM2),a research study on diabetes prevention is being conducted inEurope via an intervention on modifiable life styles known as“PLAN Study”. The work herein depicted is part of the saidEuropean study.Objective: to assess the effectiveness of an intervention programmeon changes in the life style (diet and physical exercise)to prevent the onset of DM2 in high-risk subjects.Material y methods: longitudinal prospective study in a populationsample aged 45 to 70, both genders, in a basic healtharea in Arévalo. A randomised sampling by health card wascarried out, which was subsequently stratified by area: ruraland semi-urban, with a sample size comprised of 221 people.The study was carried out in three phases: Phase 1: screeningby means of the Findrisk scale, clinical interview, anthropometrics,blood work and oral glucose tolerance test. Afterthe screening phase, subjects with a Findrisk ≥14 wereinformed of the group intervention programme; Phase 2: groupintervention, consisting of 4 theory-practical workshops; Phase3: continued intervention. Reinforcement of motivation andannual clinical visits.Results: 21 diabetic subjects were excluded. The Findrisk scorewas ≤ 14 (high risk) in 120 subjects. Prevalence of unknowndiabetes was 7,2%. Of the 66 candidates from both genders,55 (83,3%) accepted to participate in the programmeand 47 completed it. There were no (..) (AU)

Negative prognostic impact of the coexpression of epidermal growth factor receptor and c-erbB-2 in locally advanced cervical cancer.

OBJECTIVE: The objective was to determine the impact of the coexpression of epidermal growth factor receptor (EGFR) and tumor marker c-erbB-2 on disease-free survival (DFS) and pelvic relapse-free survival (PRFS) in patients with locally advanced cervical cancer (LACC) receiving concurrent chemoradiotherapy. METHODS: The expression of EGFR and c-erbB-2 was assessed by immunohistochemistry, which was centralized and blinded to outcome. Univariate and multivariate analyses were used to evaluate the impact of EGFR and c-erbB-2 on DFS and PRFS. RESULTS: 170 patients with LACC were included and received concurrent chemoradiotherapy. 25 (15%) biopsies were considered EGFR and c-erbB-2 positive; 100 (59%) were either EGFR or c-erbB-2 positive, and 45 (26%) were EGFR and c-erbB-2 negative. The 3- and 5-year DFS was 39% each for EGFR- and c-erbB-2-positive patients, 54 and 49%, respectively, for EGFR- or c-erbB-2-positive patients, and 76 and 72%, respectively, for EGFR- and c-erbB-2-negative patients (p = 0.006). EGFR- and c-erbB-2-positive tumors were significantly associated with a decrease in PRFS (hazard ratio, HR, 3.99; 95% confidence interval, CI, 1.44-11.05, p = 0.007), and DFS (HR 2.9; 95% CI, 1.26-6.66, p = 0.01). CONCLUSION: Patients with LACC coexpressing EGFR and c-erbB-2, and treated with concurrent chemoradiotherapy, had a worse clinical prognosis with shorter DFS and PRFS.