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Localization of Felis catus Papillomavirus Type 2 E6 and E7 RNA in Feline Cutaneous Squamous Cell Carcinoma.

ABSTRACT: Findings from polymerase chain reaction-based methods have suggested a role of Felis catus papillomavirus 2 (FcaPV-2) in the development of feline cutaneous squamous cell carcinoma (SCC). However, because polymerase chain reaction cannot localize deoxyribonucleic acid or ribonucleic acid within the lesion, it is difficult to differentiate a coincidental FcaPV-2 infection and a causative association. Given that a key event in the pathogenesis of human papillomavirus-induced cancer is the expression of viral E6 and E7 oncogenes, localization of FcaPV-2 E6 and E7 transcription within neoplastic cells in feline SCCs would support a causative role for this papillomavirus. Therefore, RNAscope in situ hybridization was used to localize FcaPV-2 E6 and E7 transcripts in 18 formalin-fixed paraffin-embedded samples of cutaneous SCC. Positive signals were present within 5 of 9 samples (56%) from ultraviolet-protected sites and 0 of 9 samples from ultraviolet-exposed sites. In the 4 in situ hybridization-positive samples that contained adjacent hyperplastic skin, hybridization patterns in these regions were characterized by intense nuclear signals within the superficial epidermis and punctate signals within the basal epithelial layers. However, within the 5 SCCs, punctate signals were present within all layers of the epidermis, with progressive loss of intense nuclear signals within the superficial epidermis. This hybridization pattern is consistent with unregulated E6 and E7 transcription and decreased viral replication and is similar to the pattern observed in human papillomavirus-induced cancers as they progress from hyperplastic lesions containing productive infections to nonproductive neoplasms. These findings support a causative role for FcaPV-2 in the pathogenesis of feline SCC.

SUBMITTER: Hoggard N

PROVIDER: S-EPMC6445259 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Localization of Felis catus Papillomavirus Type 2 E6 and E7 RNA in Feline Cutaneous Squamous Cell Carcinoma.

Hoggard Nathan N Munday John S JS Luff Jennifer J

Veterinary pathology 20180117 3

Findings from polymerase chain reaction-based methods have suggested a role of Felis catus papillomavirus 2 (FcaPV-2) in the development of feline cutaneous squamous cell carcinoma (SCC). However, because polymerase chain reaction cannot localize deoxyribonucleic acid or ribonucleic acid within the lesion, it is difficult to differentiate a coincidental FcaPV-2 infection and a causative association. Given that a key event in the pathogenesis of human papillomavirus-induced cancer is the expressi ...[more]

PMID: 29343198

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Project description:Patients with HPV-positive oropharyngeal cancer show better tumor response to radiation or chemotherapy than patients with HPV-negative cancer. HPV oncoprotein E6 binds and degrades a typically wild-type p53 protein product. However, HPV16 infection and p53 mutation infrequently coexist in a subset of HNSCCs. The purpose of this study was to investigate the mechanisms through which tumor biology and molecular genetic mechanisms change when two HPV-negative, p53-mutated oropharyngeal cell lines (YD8, non-disruptive p53 mutation; YD10B, disruptive p53 mutation) derived from patients with a history of heavy smoking are transfected with HPV E6 and E7 oncogenes in vitro. Transfection with HPV E6 and E7 oncogenes in YD8, reduced the abundance of proteins encoded by tumor suppressor genes, such as p-p53 and p-Rb. Cell proliferative activity was increased in the cells transfected with E6E7 compared to cells transfected with vector alone (P=0.09), whereas the invasiveness of E6E7-transfected cells was significantly reduced (P=0.02). cDNA microarray of the transfected cells with E6E7 showed significant changes in mRNA expression in several signaling pathways, including focal adhesion, JAK-STAT signaling pathway, cell cycle and p53 signaling pathway. Regarding the qPCR array for the p53 signaling pathway, the mRNA expression of STAT1 was remarkably upregulated by 6.47-fold (P<0.05); in contrast, IGF-1R was significantly downregulated by 2.40-fold in the YD8-vector compared toYD8-E6E7 (P<0.01). Finally, data collected from these two array experiments enabled us to select two genes, STAT1 and IGF-1R, for further study. In immunohistochemical study, nuclear STAT1 expression was slightly higher in HPV-positive compared to HPV-negative oropharyngeal tumors (P=0.18); however, cytoplasmic STAT1 was significantly lower in HPV-positive cases (P=0.03). IGF-1R expression levels were remarkably lower in HPV-positive compared to HPV-negative cases (P=0.01). Our data suggest that upregulated STAT1 and interferon signals by HPV16 E6 and E7 genes may play a major role in the relatively favorable prognosis for HPV-positive oropharyngeal squamous cell carcinoma cases with non-disruptive p53 mutations.

Dataset Information

Localization of Felis catus Papillomavirus Type 2 E6 and E7 RNA in Feline Cutaneous Squamous Cell Carcinoma.

Publications

Localization of Felis catus Papillomavirus Type 2 E6 and E7 RNA in Feline Cutaneous Squamous Cell Carcinoma.

Similar Datasets

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