Abstract
Tg.rasH2 mice are predisposed to hemangiosarcomas. Following the spleen, the uterus is the second most commonly affected organ in the female mice. Female mice are also predisposed to spontaneous vascular proliferative lesions on the serosal surface of the uterus, in which there is proliferation of normal vessels that are lined by well-differentiated endothelial cells. The hemangiosarcomas and vascular proliferative lesions can occur independently. In our facility, we have recorded a total of 47 uterine hemangiosarcomas in 3,985 female Tg.rasH2 mice assigned to various groups in 38 studies. Of these 47 cases, we have seen 22 (46.8%) cases where there was a clear progression of the serosal uterine vascular proliferative lesion into a hemangiosarcoma. In the remaining 25 (53.2%) cases, the uterine hemangiosarcomas involved myometrium and endometrium, but there was no serosal vascular proliferation. Based on the retrospective analysis of our data, we demonstrate that the vascular proliferative lesions noted on the serosal surfaces can progress to hemangiosarcomas and therefore these vascular proliferative lesions should be considered as preneoplastic lesions.
Highlights
The 2-year rodent carcinogenicity assays involving conventional rats and mice have been conducted for over 3 decades
The lesions were considered to be vascular proliferative lesions as long as they were restricted to the serosal surfaces and that there was no evidence of invasion of the myometrium and/or endometrium
The tumor data statistics performed on each study did not show a statistically significant increase in any of the studies for uterine hemangiosarcomas
Summary
The 2-year rodent carcinogenicity assays involving conventional rats and mice have been conducted for over 3 decades. The proliferations of vessels on the serosal surface of the uterus are normal and are lined by normal vascular endothelium These proliferative lesions can be seen on the uterine serosal surface as reddish foci, reddish discoloration, or raised nodules, whereas hemangiosarcomas noted in the uterus are usually seen as masses that occupy most of the circumference of the uterus. These so-called vascular proliferative lesions have been recorded by us and other authors in various tissues of Tg.rasH2 mice such as brain, kidneys, nasal cavity, spinal cords, urinary bladder, cervix, ovary, oviduct, and uterus.[4,5,6,7,8,9] per our records, the uterus was the most commonly affected organ with serosal vascular proliferative lesions.[8] In addition, the uterus was the second most
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