César Álvarez Marcos

Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain

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Publications (39)53.22 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. Despite therapeutic improvements, patients with sinonasal squamous cell carcinoma (SCC) still face a unfavorable prognosis and there is great need for alternative treatments.Methods. SCCNC4 cells, orginally derived from a T2N1M0 primary and untreated sinonasal SCC, were inoculated in the maxillary sinus of immunodeficient mice. Histology, invasive behavior and genetic features were evaluated and compared with the original primary tumor.Results. The mice developed tumors that invaded bone, surrounding tissues and brain, showing the same poor differentiation as the original primary tumor. Genetic analysis revealed an almost identical pattern of copy number alterations except for the deletion and loss of expression of the genes CDKN2A and PTEN.Conclusion. This paper shows the feasibility of an orthotopic mouse model of SCC of the maxillary sinus. Completed by genome-wide genetic profiling data, this model will be useful for preclinical testing of specific gene-targeted anticancer drugs. Head Neck, 2014
    Head & Neck 09/2014; DOI:10.1002/hed.23832 · 3.01 Impact Factor
  • Acta Otorrinolaringológica Española 01/2013; 64(1):86. DOI:10.1016/j.otorri.2012.09.007
  • Acta Otorrinolaringológica Española 11/2012; 64(1). DOI:10.1016/j.otoeng.2013.02.015
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    ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is a tumour type that generally carries very complex chromosomal aberrations. An interesting feature is the elevated occurrence (58 %) of whole arm translocations and isochromosomes, resulting from breakage and illegitimate recombination in centromeric or pericentromeric regions. We hypothesized that alterations in DNA methylation may play a role in the breakage of centromeric repeat sequences in these tumours. We studied the DNA methylation status of global repeats (LINE-1), subtelomeric repeats (D4Z4) and centromeric repeats (SAT-α) in relation to centromeric instability in a series of HNSCC cancer cell lines and primary tumours. We analysed the methylation status by pyrosequencing and the chromosomal aberrations by microarray CGH. We found a significant association between centromeric instability and hypomethylation of LINE-1, but not D4Z4 and SAT-α. These data suggest that centromeric instability is associated with genomic DNA hypomethylation only when occurring at specific DNA repeat sequences.
    06/2012; 35(4):259-67. DOI:10.1007/s13402-012-0085-5
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    ABSTRACT: Second primary tumors and recurrences are an important problem in patients with head and neck squamous cell carcinoma. The purpose of this study was to determine the genetic changes in tumor samples to improve knowledge of tumor progression. Copy number changes of 37 genes were analyzed by multiplex ligation-dependent probe amplification (MLPA) in 36 primary tumors and their corresponding 21 second primary tumors and 15 recurrences. CCND1 and EMS1 amplifications and gain of BCL2L1 were the most common genetic alterations in the primary tumor, second primary tumor, and recurrence samples. Gains of ERBB2 and PTPN1 were associated with recurrences. Specific genetic profiles for each group have been found. Similarities between primary tumor and second primary tumor and dissimilarity between primary tumor and recurrence suggest that clinicopathological criteria do not always accurately differentiate these entities. Genetic profiling may aid in the diagnosis and prognosis of these difficult cases.
    Head & Neck 06/2012; 34(6):830-9. DOI:10.1002/hed.21824 · 3.01 Impact Factor
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    ABSTRACT: Intestinal-type sinonasal adenocarcinoma represents 8% to 25% of all malignant sinonasal cancer and is etiologically related to occupational exposure to wood dust. Despite its clear etiology, the mechanisms behind the carcinogenic effects of wood dust are unclear. Because it is known that carcinogens can leave specific mutational fingerprints, we aimed to analyze the spectrum of TP53 mutations and to relate the findings to the wood dust etiology of the patients. Forty-four primary tumors were examined for TP53 mutations by direct sequencing. In addition, p53 protein expression was analyzed by immunohistochemistry using a tissue microarray consisting of 92 tumors. We report a frequency of 41% (18/44) TP53 mutations and 72% (66/92) p53 immunopositivity in intestinal-type sinonasal adenocarcinoma, significantly related to wood dust, but not to tobacco etiology. G→A transition (50%, 9/18 cases) was the most common alteration detected, almost exclusively found in nonsmokers, whereas G→T (27%, 5/18 cases) was detected in smokers only. These data point to wood dust exposure as the causal factor in the mutagenesis of TP53, possibly caused by reactive nitrogen species generated through a chronic inflammatory process.
    Human pathology 05/2012; 43(11):1894-901. DOI:10.1016/j.humpath.2012.01.016 · 2.81 Impact Factor
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    ABSTRACT: IntroductionPeritonsillar infection is the most frequent complication of acute tonsillitis. Peritonsillar infections are collections of purulent material, usually located between the tonsillar capsule and the superior constrictor of the pharynx. Peritonsillar infection can be divided into abscess and cellulitis.Material and methodsWe prospectively analysed the clinical data from 100 patients with peritonsillar infection from 2008 to 2010. The diagnosis of abscess or peritonsillar cellulitis was primarily based on obtaining pus through fine-needle aspiration.ResultsSeventy-seven per cent of patients had no history of recurrent tonsillitis and 55% were receiving antibiotic treatment. Sixty-two cases were peritonsillar abscess and the rest were cellulitis. Trismus, uvular deviation and anterior pillar bulging were statistically associated with peritonsillar abscess (P<.005). All patients were admitted to hospital and treated with puncture-drainage, intravenous antibiotics (amoxicillin/clavulanate in 83% of cases) and a single dose of steroids. All patients were discharged on oral antibiotic therapy. The mean length of hospital stay was 3 days and the recurrence rate was 5%.Conclusions Due to the absence of clinical practice guidelines, there are different therapeutic protocols. According to our experience, puncture-aspiration and administration of intravenous antibiotics is a safe, effective way to treat these patients. To determine the efficacy and safety of outpatient management, controlled studies would be needed.
    Acta Otorrinolaringológica Española 05/2012; 63(3):212–217. DOI:10.1016/j.otorri.2012.01.001
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    ABSTRACT: OBJETIVES: Despite improvements in the field of surgery and radiotherapy, the overall prognosis of sinonasal carcinomas is poor, mainly due to the difficulty to resect the tumour completely in this anatomically complex region. Therefore, there is great need for alternative treatments. Knowledge of the KRAS and BRAF mutational status would become clinically important with regard to the possible use of anti-EGFR therapies. DNA was extracted from paraffin embedded tumour samples from 57 cases of sinonasal squamous cell carcinoma (SNSCC) and from fresh frozen tumour samples from 58 cases of intestinal-type sinonasal adenocarcinoma (ITAC). Point mutations were analysed for KRAS exon 2 (codons 12 and 13) and BRAF (exon 15, V600E) by direct sequencing. Neither KRAS nor BRAF showed any mutations in the SNSCC, whereas 7/58 (12%) ITAC harboured KRAS mutations and no BRAF mutations. All seven cases with KRAS mutation concerned well-differentiated and less aggressive (papillary and colonic type) ITAC, all patients being woodworkers and 4/7 tobacco smokers. Neither of SNSCCs carried mutations in KRAS and BRAF and a low frequency of KRAS mutation was found in ITAC. This suggests that KRAS and BRAF mutations play a limited role in the development of sinonasal cancer and that mutation analysis is not useful as a screening test for sensitivity to anti-EGFR therapy in sinonasal cancer.
    Oral Oncology 03/2012; 48(8):692-7. DOI:10.1016/j.oraloncology.2012.02.018 · 3.03 Impact Factor
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    ABSTRACT: Peritonsillar infection is the most frequent complication of acute tonsillitis. Peritonsillar infections are collections of purulent material, usually located between the tonsillar capsule and the superior constrictor of the pharynx. Peritonsillar infection can be divided into abscess and cellulitis. We prospectively analysed the clinical data from 100 patients with peritonsillar infection from 2008 to 2010. The diagnosis of abscess or peritonsillar cellulitis was primarily based on obtaining pus through fine-needle aspiration. Seventy-seven per cent of patients had no history of recurrent tonsillitis and 55% were receiving antibiotic treatment. Sixty-two cases were peritonsillar abscess and the rest were cellulitis. Trismus, uvular deviation and anterior pillar bulging were statistically associated with peritonsillar abscess (P<.005). All patients were admitted to hospital and treated with puncture-drainage, intravenous antibiotics (amoxicillin/clavulanate in 83% of cases) and a single dose of steroids. All patients were discharged on oral antibiotic therapy. The mean length of hospital stay was 3 days and the recurrence rate was 5%. Due to the absence of clinical practice guidelines, there are different therapeutic protocols. According to our experience, puncture-aspiration and administration of intravenous antibiotics is a safe, effective way to treat these patients. To determine the efficacy and safety of outpatient management, controlled studies would be needed.
    Acta Otorrinolaringológica Española 03/2012; 63(3):212-7. DOI:10.1016/j.otoeng.2012.01.013
  • César Álvarez Marcos
    04/2011; 62(2):172. DOI:10.1016/S2173-5735(11)70032-1
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    ABSTRACT: Occupational exposure to wood dust is a strong risk factor for the development of intestinal-type sinonasal adenocarcinoma (ITAC); however, knowledge on possible precursor lesions or biomarkers is limited. Fifty-one samples of tumor-adjacent mucosa and 19 control samples of mucosa from the unaffected fossa of ITAC patients were evaluated for histological changes and p53 protein expression. Mild dysplasia was observed in 14%, cuboidal metaplasia in 57%, intestinal metaplasia in 8%, squamous metaplasia in 24%, and cylindrocellular hyperplasia in 53% of cases. P53 immunopositivity was generally weak occurring most frequently in squamous metaplasia. Wood dust etiology did not appear of influence on the histological changes, but p53 showed a tendency for higher positivity. Dysplasia adjacent to tumor was indicative of subsequent development of recurrence. In conclusion, precursor lesions do occur in mucosa adjacent to ITAC. This is clinically important, because it may justify the screening of high-risk individuals such as woodworkers.
    04/2011; 2011(2):230147. DOI:10.4061/2011/230147
  • César Álvarez Marcos
    Acta Otorrinolaringológica Española 03/2011; 62(2):172. DOI:10.1016/j.otorri.2010.11.002
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    ABSTRACT: Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor etiologically related to professional exposure to wood dust. The overall prognosis is poor, mainly due to the difficulty to resect the tumor completely in this anatomically complex region. Therefore, there is great need for alternative treatments. However, the lack of a good tumor model system for ITAC has hampered the development and testing of new therapeutic agents. Here, we report the establishment and characterization of the first human ITAC cell line named ITAC-3. The cell line was initiated from small explants of a T4bN0M0 colonic type ITAC from the ethmoid sinus. Growth and invasion parameters as well as genetic characteristics were analyzed. The population doubling time was 18 h and the cell line was capable of invasion in matrigel. Chromosomal analysis showed a tetraploid karyotype with both numerical and structural aberrations. High resolution microarray CGH analysis identified many copy number alterations, including homozygous deletions. TP53 carried a mutation c.818G>T in exon eight concurring with a strong nuclear protein overexpression. Immunohistochemical analysis showed protein overexpression of EGFR and normal expression of β-catenin and p16. This is the first report of the establishment of a cell line derived from a primary ITAC. The genomic profile of the cell line was the same as the primary tumor from which it was derived. This new cell line will be a useful tool for the development and testing of new therapeutic agents for this tumor type.
    02/2011; 34(1):23-31. DOI:10.1007/s13402-010-0002-8
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    ABSTRACT: The aim of this study was to analyze genetic alterations in the transformation-progression model of laryngeal tumors. Copy number changes of 37 genes were analyzed by multiple ligation-dependent probe amplification (MLPA) in 94 tissue samples. In the smoker normal mucosa group TP53 loss was predominant, whereas in the precursor lesions CDKN2A loss and CDKN2D gain were most frequent. Precursor lesions with progression presented CTNNB1 loss. In the carcinoma group the most common changes were CDKN2A, MLH1, CTNNB1, and CASP6 losses and RECQL4, CCND1, and EMS1 gains. Positive lymph node primary tumors were related to TP53, IL1A, and RB1 losses and STK11 gain. The lymph node metastases differed from their corresponding primary tumor in LMNA, RECQL4, and IGF1R losses, and N33 and CDKN2D gains. Genetic changes and new key genes were found to be associated with specific steps. We included new steps, not presented in the classic models: normal mucosa tobacco exposed, positive lymph node primary tumor, and corresponding lymph node metastases.
    Head & Neck 02/2011; 33(2):216-24. DOI:10.1002/hed.21432 · 3.01 Impact Factor
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    ABSTRACT: Introduction and objectivesSquamous cell carcinomas at the base of the tongue are usually diagnosed at advanced stages, and their optimal treatment has not been established. The aim of this study was to describe the functional and oncological outcomes of patients with base of tongue carcinomas treated with surgery.
    Acta Otorrinolaringológica Española 09/2010; 61(5). DOI:10.1016/j.otorri.2010.04.003
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    ABSTRACT: Squamous cell carcinomas at the base of the tongue are usually diagnosed at advanced stages, and their optimal treatment has not been established. The aim of this study was to describe the functional and oncological outcomes of patients with base of tongue carcinomas treated with surgery. A retrospective study on 132 patients with base of tongue carcinoma surgically treated in our hospital between 1990 and 2007 was carried out. One patient (0.75%) was in stage I, 8 (6%) were in stage II, 15 (11%) in stage III, 91 (69%) in stage IVA, and 17 (13%) with stage IVB. A total of 92 (70%) patients received postoperative radiotherapy. Eighty-seven patients (66%) had recurrence: 23 patients (17%) had local recurrence, 15 (11%) regional, 20 (15%) locoregional, 16 (12%) locoregional and distant, and 9 (7%) distant metastases. The disease-specific survival was 34% at 5 years (100% for stages I and II, 44% for stage III, 28% for stage IVA and 12% for IVB; p=0.0004). Multivariate analysis showed two variables independently associated with worse survival: lymph node metastases classified as N2-3 (p=0.016) and primary tumours classified as T3-4 (p=0.040). Adequate oral intake was achieved by 96% of the patients and 79% could be decannulated. The prognosis of squamous cell carcinomas of the base of the tongue is poor, especially in advanced stages. Surgical treatment provides oncological and functional results similar to other therapeutic modalities.
    Acta Otorrinolaringológica Española 01/2010; 61(5):351-7. DOI:10.1016/S2173-5735(10)70064-8
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    ABSTRACT: Inverted papillomas are benign sinonasal lesions that arise primarily from the lateral nasal wall which are characterized by their tendency to recur and propensity to be associated with malignancy. The aim of this work is to analyze our experience in the treatment of these lesions, especially through the endoscopic approach. We present 61 cases of sinonasal inverted papillomas that were treated at our hospital since 1983. The patients were studied by age, gender, site of presentation of the tumor, symptoms, radiologic studies, surgical treatment and evolution. The mean follow-up was 51 months (range 6-228 months). Thirty eight of the patients (62%) were males and 23 females (38%). The average age was 58 years (range 22-80). The most common symptom was unilateral nasal obstruction in 91% of the cases, followed by rhinorrhea in 46%. The most frequent location was the ethmoid region in 51% of cases, followed by the maxillary sinus in 28% and the lateral nasal wall in 21% of the cases. 78% of cases had associated sinusitis and the 43% polyposis. Tumours were classified with the Krouse staging system as follows: 35% stage I, 37% stage II, 18% stage III and 8% stage IV. 37% of the patients had bony erosion in the CT scan. Six of the 42 patients treated by endoscopic procedures presented recurrence (14%), compared with 6 of the 9 patients (67%) who were treated by open approaches. The average time to the recurrence was 41 months. 17% of the patients had malignant inverted papillomas, nine of them diagnosed from the beginning as malignant neoplasies and one which became malignant during follow up. The endoscopic approach is the method of choice for the treatment of the majority of inverted papillomas. The close follow up of the patient for a large period of time is necessary for the early detection of recurrence and to allow for surgical salvage.
    Acta Otorrinolaringológica Española 12/2009; 60(6):402-8. DOI:10.1016/S2173-5735(09)70166-8
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    ABSTRACT: IntroductionInverted papillomas are benign sinonasal lesions that arise primarily from the lateral nasal wall which are characterized by their tendency to recur and propensity to be associated with malignancy. The aim of this work is to analyze our experience in the treatment of these lesions, especially through the endoscopic approach.
    Acta Otorrinolaringológica Española 11/2009; 60(6). DOI:10.1016/j.otorri.2009.05.002
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    ABSTRACT: To determine the usefulness of specific and reliable serum biomarkers to predict cervical lymph node metastasis. A cross-sectional study of cases and controls. Thirty-nine serum samples of head and neck squamous cell carcinoma were collected from patients during neoplasm resection. Another 10 serum samples were collected from healthy individuals as a control group. Selected serum biomarkers were E-cadherin, MMP-2, MMP-9, active MMP-13, and p53 autoantibodies. We found a correlation between active MMP-13 (>685 pg/mL; ROC curve analysis 95% CI for sensitivity 79.6-99.3; specificity 49.2-95.1; positive predictive value 65-100; and negative predictive value 36-100) as well as the presence of p53 autoantibodies and lymph node metastasis. Multimarker analysis using MMP-13 and p53 autoantibodies together provided better sensitivity (76%) and specificity (100%). The combined determination of active MMP-13 and p53 autoantibodies could improve diagnosis of lymphatic metastasis in head and neck squamous cell carcinoma and aid therapeutic decision making.
    Otolaryngology Head and Neck Surgery 03/2009; 140(3):375-80. DOI:10.1016/j.otohns.2008.12.026 · 1.72 Impact Factor
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    ABSTRACT: Serum glycoproteins and prognosis in cancer of the head and neckAlpha 1 acid glycoprotein, alpha 1 antitrypsin, haptoglobin, alpha 2 HS glycoprotein and prealbumin were studied in 44 patients with cancer of the head and neck and in a control group. The three primary glycoproteins were considerably elevated in the patients, particularly in stage IV. In the group of patients who died before 30 months after treatment the haptoglobin was significantly elevated compared to those who survived beyond this point. Only values for the alpha 1 acid glycoprotein greater than 150 mg/dl were a prognostic factor of similar precision to that of stage IV. This correlation could not be shown for the other glycoproteins.
    Clinical Otolaryngology 01/2009; 11(1):41 - 45. DOI:10.1111/j.1365-2273.1986.tb01991.x · 2.39 Impact Factor

Publication Stats

239 Citations
53.22 Total Impact Points

Institutions

  • 2005–2012
    • Hospital Universitario Central de Asturias
      • Department of Otolaryngology
      Oviedo, Asturias, Spain
  • 1988–2011
    • University of Oviedo
      • • Área de Otorrinolaringología
      • • Department of Biochemistry and Molecular Biology
      Oviedo, Asturias, Spain
  • 1999–2009
    • Hospital Valle Del Nalon
      Galicia, Spain
  • 2003
    • Hospital Central de Asturias
      Oviedo, Asturias, Spain