Clinical observations and epidemiologic analyses conducted for more than a decade have established the existence of a strong relationship between vaccination in cats and development of soft tissue sarcomas at the injection sites.1–6 For the cervical and interscapular regions, where vaccines were usually administered in the past, the risk of tumor development is 50% higher for cats receiving a single vaccination, compared with cats not receiving any vaccines.4 This risk further increases to 127% with 2 vaccinations and to 175% with ≥ 3 vaccinations at the site. Although the actual incidence is not known, it is estimated that between 3 to 13 cats develop VAFS for every 10,000 vaccines administered.7,8 Because most of the household cat population in the United States (which is currently > 73 million) receives ≥ 1 vaccination each year, a sizable number of cats are at risk of developing this disease.9
Vaccine-associated feline sarcomas are highly invasive tumors with poorly defined margins.5,6,10–14 The tumors are predominantly fibrosarcomas and malignant fibrous histiocytomas, although other histologic subtypes have occasionally been reported.6,10,11 These aggressive tumors are characterized by severe pleomorphism, high mitotic indices, and central areas of necrosis. The recurrence rate after surgery has been estimated at > 60%, with most such recurrences appearing within 6 months of surgical excision of the primary tumor.5 Distant metastases (primarily to the lung) are also detected in 28% of affected cats within approximately 2 years of diagnosis of the primary tumor.14,15 Not surprisingly, early detection and aggressive excision of tumors at referral hospitals lead to a better outcome, extending the median DFI from just 66 days to well over 300 days.15,16
The purpose of the study reported here was to determine somatic alterations in p53 in cats with VAFS. The p53 tumor suppressor gene plays an important role in cellular homeostasis.17 Upregulation and stabilization of the p53 protein in cells with DNA damage lead to cell cycle arrest in the G1 phase, thereby allowing various repair enzymes to restore the genomic integrity. The protein also serves as a switch, sending cells with excessive or irreparable damage into a process of programmed cell death. Somatic alterations of p53 are frequently found in tumors of human and animals and can lead to an aggressive phenotype.17,18 Because somatic alterations of the p53 tumor suppressor gene are frequently associated with tumor aggressiveness, we have analyzed the most commonly affected regions of the gene by automated DNA sequence analysis in 27 cats with VAFS. We here present strong evidence for LOH at this locus in vaccine-site tumors and further show a significant negative association of such allelic deletion with time to local disease recurrence and overall prognosis.
Vaccine-associated feline sarcoma
Loss of heterozygosity
Single nucleotide polymorphism
Vacutainer blood collection tube, Becton, Dickinson & Co, Franklin Lakes, NJ
QIAamp tissue kit, QIAgen Inc, Valencia, Calif
Novagen, EMD Biosciences, Madison, Wis
AmpliTaq Gold DNA polymerase with GeneAmp 10X PCR gold buffer, PE Applied Biosystems, Foster City, Calif
Microcon YM-100 centrifugal filtration unit, Millipore Corp, Bedford, Mass
AmplitaqFS Dye-terminator kit, PE Applied Biosystems, Foster City, Calif
BigDye terminator cycle sequencing kits, version 3.1, PE Applied Biosystems, Foster City, Calif
ABI model 377 DNA sequencer, PE Applied Biosystems, Foster City, Calif
EditSeq, DNASTAR Inc, Madison, Wis
MegAlign, DNASTAR Inc, Madison, Wis
StatView version 8.2, SAS Institute Inc, Cary, NC
GraphPad Software Inc, San Diego, Calif.
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Cohen M, Wright JC & Brawner WR, et al. Use of surgery and electron beam irradiation, with or without chemotherapy, for treatment of vaccine-associated sarcomas in cats: 78 cases (1996–2000). J Am Vet Med Assoc 2001;219:1582–1589.
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Primers for PCR amplification of feline p53 segments.
|Segments||Primers||Amplicon size (bp)|
|Exon 5 + intron 5 + exon 6||5′-TACTCCCCTCCCCTCAACAA-3′ and||386|
|Exon 7 + intron 7 + exon 8||5′-GTCGGCTCTGACTGTACC-3′ and||519|
|Intron 7 (partial) + exon 8||5′-CTTTGGGACCTTCTCTTACC-3′ and||418|
|+ intron 8 + exon 9 (partial)||5′-ATTCTCCATCCAGTGGCTTC-3′|