title: Simultaneous detection of human papillomavirus integration and c-MYC gene amplification in cervical lesions: an emerging marker for the risk to progression.
abstract: OBJECTIVE
  The persistence of high-risk oncogenic human papillomavirus (HR-HPV) infection and its integration into the host genome are key steps in the induction of malignant alterations. c-MYC chromosome region is a frequent localization for HPV insertion that has been observed in chromosome band 8q24 by fluorescence in situ hybridization (FISH). We report the HPV viral integration and amplification patterns of the c-MYC gene in cytological smears with FISH as a potential biomarker for the progression of squamous intraepithelial lesions (SIL).
  
  
  METHODS
  HPV detection and genotyping by polymerase chain reaction (PCR) and FISH analysis by "Vysis Cervical FISH Probe" kit (ABBOTT Molecular Inc.) were performed in 37 cervical samples including 8 NILM, 7 ASC-US, 7 LSIL, 3 ASC-H, 7 HSIL and 5 SCC.
  
  
  RESULTS
  The results show concordance between FISH and PCR techniques for HPV detection. The majority of the samples contained HR-HPV, the majority being -16 and -18 genotypes. HPV integration as determined by FISH was most frequent in high-risk lesions. The c-MYC gene amplification was found only in HPV-positive samples and was detected primarily in high-risk lesions and in cells with an integrated form of HPV.
  
  
  CONCLUSIONS
  HPV integration and c-MYC gene amplification detected by FISH could be an important biomarker for use in clinical practice to determine SIL with a risk of progression.
authors: Laboratory of Clinical Cytology and Semen Analysis, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, PR, 87020900, Brazil.
authors: Fabrícia
authors: F
authors: Gimenes
authors: Laboratory of Clinical Cytology and Semen Analysis, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, PR, 87020900, Brazil.
authors: Raquel Pantarotto
authors: RP
authors: Souza
authors: Laboratory of Clinical Cytology and Semen Analysis, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, PR, 87020900, Brazil.
authors: André Luelsdorf Pimenta
authors: AL
authors: de Abreu
authors: Laboratory of Clinical Cytology and Semen Analysis, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, PR, 87020900, Brazil.
authors: Monalisa Wolski
authors: MW
authors: Pereira
authors: Laboratory of Clinical Cytology and Semen Analysis, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, PR, 87020900, Brazil.
authors: Marcia Edilaine Lopes
authors: ME
authors: Consolaro
authors: Laboratory of Clinical Cytology and Semen Analysis, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, PR, 87020900, Brazil. vaniasela@gmail.com.
authors: Vânia Ramos Sela
authors: VR
authors: da Silva
mesh_terms: D000328:Adult; D018450:Disease Progression; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics*; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics; D052161:Human papillomavirus 18 / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000235:genetics / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000235:genetics / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000821:virology
keywords: Biomarkers; Cervical cancer; Human papillomavirus; Integration; c-MYC