A Subset of Equine Gastric Squamous Cell Carcinomas Is Associated With Equus Caballus Papillomavirus-2 Infection

Abstract

Squamous cell carcinoma (SCC) is the most common neoplasm of the equine stomach. However, the mechanisms underlying malignant transformation are unknown. As Equus caballus papillomavirus-2 (EcPV-2) is a likely cause of some genital SCCs, we hypothesized that EcPV-2 is associated with a subset of equine gastric SCCs. To this aim, we performed polymerase chain reaction (PCR) and in situ hybridization (ISH) for EcPV-2 E6/ E7 oncogenes on 11 gastric SCCs and on gastric samples from 15 control horses with no SCC. PCR for EcPV-2 was positive in 7/11 (64%) gastric SCCs; non-SCC gastric samples were all negative. Intense hybridization signals for EcPV-2 E6/E7 nucleic acid were detected by ISH within tumor cells in 5/11 (45%) gastric SCCs, including distant metastases. No hybridization signals were detected within any of the non-SCC gastric cases. This study provides support for a potential association between EcPV-2 infection and a subset of equine gastric SCC.

Keywords: Equus caballus papillomavirus; horses; in situ hybridization; oncogenic viruses; squamous cell carcinoma; stomach.

Figures 1–4.

Horse No. 1. Figures 1–3. Mucosal hyperplasia overlying squamous cell carcinoma (SCC); stomach. Figure 1. (a) Hyperplastic gastric squamous epithelium and islands of neoplastic squamous epithelium within the deeper submucosa. Hematoxylin and eosin (HE). (b) Intense hybridization signals (red) are present within the overlying mucosal and deeper islands of neoplastic cells. In situ hybridization (ISH), EcPV-2 E6/E7 probe. Figure 2. (a) Higher magnification of the hyperplastic gastric squamous epithelium. HE. (b) Intense hybridization signals are present within the nuclei of the hyperplastic epithelium. ISH, EcPV2 E6/E7 probe. (c) No hybridization signals are present using the negative control probe. ISH, DapB probe. Figure 3. (a) Higher magnification of invasive islands of neoplastic squamous epithelial cells within the submucosa. Dot-like hybridization signals are present within the nuclei and cytoplasm of neoplastic cells. Intense diffuse hybridization signals are present within the nuclei of some of the neoplastic cells. In situ hybridization (ISH), EcPV-2 E6/E7 probe. (b) No hybridization signals are present using the negative control probe. ISH, DapB probe. Figure 4. Metastatic SCC; spleen. (a) Island of neoplastic squamous epithelium within the spleen. HE. (b) Strong dot-like hybridization signals are present within the nuclei and cytoplasm of neoplastic cells. Intense diffuse hybridization signals are present within the nuclei of some of the neoplastic cells. In situ hybridization (ISH), EcPV-2 E6/E7 probe. (c) No hybridization signals are present using the negative control probe. ISH, DapB probe.