title: Role and predictive strength of transglutaminase type 2 expression in premalignant lesions of the cervix.
abstract: The demonstration that type 2 transglutaminase (TG2) can incorporate polyamine into the E7 oncoprotein of human papillomavirus (HPV) type 18 has led to the hypothesis that TG2 can have a role in the host cellular response to HPV infection. The aim of this study was to investigate whether HPV-related pathology, in infected human cervical epithelium, was associated with modulation of TG2 expression. Normal controls and HPV-infected cervical biopsies were analyzed for the expression of TG2, and the findings were compared with lesion grade. The correlation between TG2 expression and p16, a marker for HPV-induced dysplasia, and the retinoblastoma protein (Rb), a target of the E7 protein of HPV, was also investigated. Results obtained showed that TG2 was absent in normal squamous mucosa, whereas it was present in 100% CIN I lesions. Low-grade lesions showed significantly higher TG2 expression than high-grade lesions (P<0.0001). In 94% of CIN I more than 50% of the cells were positive for TG2, with a strong staining intensity (+3), whereas a decreased staining intensity and a low number of positive cells were found in CIN II/III. In CIN I cases, both nuclear and cytoplasmic staining were found in cells exhibiting classical morphological features of HPV infection. In addition, during progression from low-grade squamous intraepithelial lesions to severe dysplasia, TG2 expression was inversely correlated with p16 (Pearson: -0.930), whereas a positive correlation was observed between the expression of TG2 and pRb (Pearson: 0.997). TG2 is expressed in HPV infection as an early phenomenon, not restricted to high-risk genotypes. TG2 upregulation is probably part of host cell reaction against HPV-induced tissue modification. It may act as a cellular antioxidant defense factor, playing an important role in counteracting oxidative damage in neoplastic disease.
authors: Department of Pathology, INMI-IRCCS Lazzaro Spallanzani, Rome, Italy.
authors: Franca
authors: F
authors: Del Nonno
authors: Giuseppe
authors: G
authors: Pisani
authors: Paolo
authors: P
authors: Visca
authors: Fabrizio
authors: F
authors: Signore
authors: Lucia Rosalba
authors: LR
authors: Grillo
authors: Andrea
authors: A
authors: Baiocchini
authors: Anna Rosa
authors: AR
authors: Garbuglia
authors: Sara
authors: S
authors: Sepe
authors: Mauro
authors: M
authors: Piacentini
authors: Laura
authors: L
authors: Falasca
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D002584:Cervix Uteri / Q000201:enzymology / Q000473:pathology / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications / Q000201:enzymology / Q000473:pathology; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000201:enzymology / Q000821:virology; D011237:Predictive Value of Tests; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D016160:Retinoblastoma Protein / Q000378:metabolism; D012189:Retrospective Studies; D011503:Transglutaminases / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000201:enzymology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000201:enzymology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins