Role and predictive strength of transglutaminase type 2 expression in premalignant lesions of the cervix View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-06

AUTHORS

Franca Del Nonno, Giuseppe Pisani, Paolo Visca, Fabrizio Signore, Lucia Rosalba Grillo, Andrea Baiocchini, Anna Rosa Garbuglia, Sara Sepe, Mauro Piacentini, Laura Falasca

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. More... »

PAGES

855

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/modpathol.2011.40

DOI

http://dx.doi.org/10.1038/modpathol.2011.40

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1034725964

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21441900


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