APPLIED IMMUNOHISTOCHEMISTRY AND MOLECULAR MORPHOLOGY
Abstract
The availability of a new E7 mAb based immunohistochemistry (IHC) detection assay, Cervimax, allowed for the first time reliable testing of the E7 protein marker in formalin-fixed and paraffin-embedded tissues from cervical lesions. E7 specific IHC staining patterns were compared with those patterns of cervical cancer biomarkers, including the viral capsid protein L1 and the surrogate biomarkers p16INK4A, p53, hTERT, ubiquitin and Ki67. The use of a tissue microarray of 138 cervical tissue cores from different pathological stages allowed for a first profiling of the various markers in comparison to E7. Cervimax staining patterns closely overlap with those from p16INK4A and hTERT in IHC staining for high-grade cervical intraepithelial lesions (H-CIN) and squamous cell carcinoma (SCC).. In SCC, E7 immunostaining matched better to hTERT and ubiquitin profiles. On the contrary, the pattern of E7 and L1 were different in all the squamous lesions. The nuclear staining of E7 significantly discriminates between L-CIN and H-CIN in the basal, parabasal and superficial layers.
The results obtained in the presented pilot study suggest E7 as a valid candidate biomarker for all the stages of the malignant progression of cervical cancer, however more extensive studies are needed to confirm the causal effect of the oncoprotein E7 in the diagnosis of HPV induced diseases. These results also suggest that the diagnostic interpretation of cervical lesions could be increased by the combination of E7 and L1 staining in the evaluation of risk of progression, because related to different phases of viral integration.
