Abstract
BackgroundThe medical management of low-grade squamous intraepithelial lesions (LSIL) is variable, thus a biomarker could assist with the clinical conduct. Type 2 transglutaminase (TG2) has been proposed as a cellular-interfering factor in HPV infection and carcinogenesis. Therefore, this study has the objective of evaluating TG2 expression in LSIL and high-grade squamous intraepithelial lesions (HSIL) and of relating it to the different HPV viral types.MethodsThis study included 146 patients with suspected LSIL or HSIL detected in routine conventional Papanicolaou tests. The presence of HPV DNA and viral typing was defined by the polymerase chain reaction method (PCR). TG2 Immunohistochemistry (IHC) was conducted according to the manufacturer's instructions; IHC was carried out in an Autosteiner-Link 48 Dako equipment. IHC quantitation was performed by relative expression and by using the software Image J. Qualitative variables, such as frequencies and proportions, were compared by using the χ2 test for independent samples. For comparison of the qualitative to the quantitative data, nonparametric Mann-Whitney test was used.ResultsThe association between histopathological examination and TG2 was statistically significant (p <0.05). Results showed that patients with normal cervical histopathology and LSIL are locally associated with TG2 expression levels >50% (p <0.05), and patients with HSIL are associated with no TG2 expression (p <0.05). The analysis of the samples with the Image J software shows a significant (p <0,001) decrease in TG2 immunostaining in HSIL if compared to normal and to LSIL samples. This demonstrates a correlation between the relative quantification and the results provided by Image J. Analysis of HPV types showed a significant association with HPV11 (p = 0.031). This indicates that patients with HPV type 11 had higher TG2 values than patients with different types. Image J analysis showed no significant association between TG2 and HPV viral types.ConclusionThe present data suggest that TG 2 has a high expression in LSIL and normal tissues, and decreased in HSIL. We also observed that its expression is associated with HPV11.
Highlights
The medical management of low-grade squamous intraepithelial lesions (LSIL) is variable, a biomarker could assist with the clinical conduct
In the LSIL group immunostaining was 74.7%, and in the highgrade squamous intraepithelial lesions (HSIL) group there was an average expression of 22.3% (Table 1), non-dysplastic cells were recorded in LSIL and/or HSIL
Our results show that LSIL presented high levels of the enzyme, while in HSIL these levels are decreased, which can be related to the absence of human papillomavirus (HPV) 11 in this samples
Summary
The medical management of low-grade squamous intraepithelial lesions (LSIL) is variable, a biomarker could assist with the clinical conduct. This study has the objective of evaluating TG2 expression in LSIL and highgrade squamous intraepithelial lesions (HSIL) and of relating it to the different HPV viral types. HPV prevalence ranges from 13.7% to 54.3% according to the studied population and geographic area in Brazil [2]. It is characterized by uncontrolled replication of the organ epithelium, which compromises the underlying tissue (stroma) and may invade adjacent or distant structures and organs.
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