title: Expressions of E2 and E7-HPV16 proteins in pre-malignant and malignant lesions of the uterine cervix.
abstract: Continuous production of the E7 protein from different types of high risk human papilloma virus (HPV) is required for progression of malignancy. We developed antibodies against HPV type 16 E7 and E2 proteins to evaluate their utility as markers for diagnosis during early stages of cervical cancer. Forty biopsies from uterine cervices were diagnosed as low grade intraepithelial lesion (LSIL), high grade intraepithelial lesion (HSIL), squamous carcinoma (SC), in situ adenocarcinoma (ISA) and invasive adenocarcinoma (AC), all of which were infected with HPV 16. Immunohistochemistry was used to investigate the expressions of E7 and E2 (both from HPV 16) and p16. P16 was expressed in eight of 12 LSILs, in all HSILs, in 16 of 18 SC and in all ACs. E2 was expressed in six of 12 LSILs. E7 was positive in eight of 12 LSILs and in all HSIL and carcinomas. The expressions of E2 and E7 of HPV16 related to p16 expression confirmed the value of the viral oncogenic proteins as complementary to histology and support the carcinogenic model of the uterine cervix, because HPVDNA integration into cellular DNA implies the destruction of the gene encoding E2, which suppresses the expression of the E6 and E7 oncoproteins. E2 from HPV16 could be marker for LSILs, while E7 could be a marker for progression of LSILs to HSILs in patients infected by HPV16, because viral typing has little positive predictive value.
authors.affiliation: a Furtwangen University , Furtwangenim, Schwarzwald , Germany.
authors.forename: N
authors.initials: N
authors.lastname: Ramirez
authors.affiliation: b Division of Cytology, Department of Clinical Biochemistry , Clinical Hospital (UBA), INFIBIOC , Córdoba , Argentina.
authors.forename: F
authors.initials: F
authors.lastname: Guerra
authors.affiliation: c CONICET, Foundation Institute Leloir , Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Camporeale
authors.affiliation: d Molecular Biology Laboratory, Fares Taie Institute , Mar del Plata, Buenos Aires , Argentina.
authors.forename: S
authors.initials: S
authors.lastname: Quintana
authors.affiliation: e Department of Pathology , Clinical Hospital (UBA) Córdoba , Argentina.
authors.forename: L B
authors.initials: LB
authors.lastname: Diaz
authors.affiliation: f Gynecology Oncology Service, Oncology Hospital María Curie , Argentina.
authors.forename: N
authors.initials: N
authors.lastname: Cuneo
authors.affiliation: g Gynecology Service, Clinical Hospital (UBA) Córdoba , Argentina.
authors.forename: J
authors.initials: J
authors.lastname: Villacorta Hidalgo
authors.affiliation: h Cervical Pathology, Clinical Hospital (UBA) Córdoba , Argentina.
authors.forename: S A
authors.initials: SA
authors.lastname: Tatti
authors.affiliation: c CONICET, Foundation Institute Leloir , Argentina.
authors.forename: L G
authors.initials: LG
authors.lastname: Alonso
authors.affiliation: c CONICET, Foundation Institute Leloir , Argentina.
authors.forename: S S
authors.initials: SS
authors.lastname: Borkosky
authors.affiliation: c CONICET, Foundation Institute Leloir , Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Prat Gay
authors.affiliation: b Division of Cytology, Department of Clinical Biochemistry , Clinical Hospital (UBA), INFIBIOC , Córdoba , Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Palaoro
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009363:Neoplasm Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: E2; E7; HPV16; adenocarcinoma; biomarkers; high grade intraepithelial lesion; immunohistochemistry; invasive adenocarcinoma; low grade intraepithelial lesion; p16; p53; squamous carcinoma; uterus