Abstract

Wild California sea lions (Zalophus californianus) ranging along the west coast of the United States have the highest prevalence of cancer amongst all marine mammal species.^1,2,3 Urogenital carcinoma has been identified in approximately 20% of adult sea lions necropsied at California rehabilitation centers and animals in managed care facilities.^1,2,3 Early lesions (carcinoma in situ) have also been found in 20–70% of sea lions removed from Columbia River for management purposes (pers comm J. Burco). This cancer originates in the genital tract and metastasizes aggressively resulting in stranding or death. Blood biomarkers are a tool commonly used in human medicine for the detection of early-stage metastatic cancers and provide a minimally invasive staging and monitoring method to facilitate prognosis.^4,5 Otarine Herpesvirus 1 (OtHV1) is a sexually transmitted herpesvirus that plays a causal role in development of urogenital carcinoma and is highly expressed in tumor cells.^6,7 Histologic evaluation of the primary tumor site in sea lions with metastatic disease often have rafts of metastatic cells in nearby blood vessels. The objective of this study was to determine if OtHV1 in blood can be used as a biomarker to predict whether a sea lion has metastatic urogenital carcinoma.

Blood (serum, plasma, or buffy coat) and genital tissue (penis or cervix) were collected from sea lions and tested for OtHV1 using quantitative polymerase chain reaction.⁵ All cases received necropsies and histologic examination to classify cases as cancer (n=16) or non-cancer (control; n=18). Cancer cases were further designated as non-invasive (carcinoma in situ; n=9) or metastatic (n=7). Detection of OtHV1 in blood of control, carcinoma in situ and cancer cases were compared to see if circulating herpesvirus was predictive of a patient having metastatic urogenital carcinoma.

OtHV1 was identified in the genital tract of 56% (10/18) controls, 100% (9/9) carcinoma in situ and 100% (7/7) metastatic cases. OtHV1 was detected in blood of 86% (6/7) of metastatic carcinoma cases, 22% (2/9) of carcinoma in situ cases and 11% (2/18) of non-cancerous cases. There was no significant difference between presence of OtHV1 in the blood samples of control and carcinoma in situ cases (Fisher’s exact test p=0.582). There was a significant difference in the detection of OtHV1 in blood samples from metastatic cases compared to carcinoma in situ (Fisher’s exact test p=0.041) and control cases (Fisher’s exact test p=0.001).

These results indicate that detection of OtHV1 in blood samples may be indicative of metastatic urogenital carcinoma in California sea lions. There were 4/27 (15%) carcinoma in situ and control cases that also tested positive for OtHV1 in blood; however, this method is not definitive for staging metastatic disease. Of the two control and two carcinoma in situ cases that tested positive, three had evidence of generalized immune suppression or severe underlying disease, which may explain why herpesvirus was identified in the blood of these patients. These results support that OtHV1 may be a potential blood biomarker for metastatic disease in sea lions with urogenital carcinoma, and also may be suggestive of immune suppression.

Acknowledgements

The authors wish to thank the staff and volunteers at Pacific Marine Mammal Center, The Marine Mammal Center, and the Oregon Department of Fish and Wildlife for their contributions to this study. Rescue and rehabilitation activities were conducted under a stranding agreement with NOAA. This work could not have been complete without the financial support of the International Association of Aquatic Animal Medicine’s Medway Scholarship program and the Pacific Marine Mammal Center’s Ocean Club.

Literature Cited

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