Immunohistochemical Characterization of Canine Transmissible Venereal Tumor

Abstract

Abstract. The collective immunohistochemical expression of human lysozyme, human alpha-1 -antitrypsin, human CD3 antigen, calf vimentin, human keratins, human lambda light chains, canine immunoglobulins IgG, IgM, and bovine protein S-100 has been analyzed on formalin-fixed, paraffin-embedded tissue sections of 25 spontaneous canine transmissible venereal tumors (CTVT) from both genital and extragenital locations using the avidin-biotin-peroxidase complex technique. Lysozyme immunoreactivity was detected in 10/25 CTVT, alpha-1-antitrypsin in 14/25 CTVT, and vimentin in 25/25 CTVT. All CTVT cells were negative to keratins 5 + 8 of the Moll catalogue (RCK-102), S-100 protein, lambda light-chain immunoglobulins, IgG, IgM, and CD3 antigen. The intratumoral T-and B-lymphocyte infiltrate was differentiated using CD3 antigen, lambda light-chain immunoglobulins, IgG, and IgM, and this technique could be useful to evaluate the regressive or progressive growth stage of venereal tumors. Our findings support the hypothesis of a histiocytic immunophenotype for CTVT, and these staining techniques could be used in the differential diagnosis with lymphomas.Key words: Dogs; immunocytochemistry; round cell tumors; transmissible venereal tumors.Canine transmissible venereal tumor (CTVT) is a round cell neoplasm occurring on external genital mucosae and is transmitted by cell implantation during coitus, licking, or other interaction between an affected dog and a susceptible host in endemic regions.44 Although the tumor primarily spreads locally to the external genitalia21 and metastasis is rare, it has also been reported in the inguinal lymph nodes, skin, lips, and buccal and nasal mucosa1, 3,25,26,35,39 and less frequently in the tonsils, liver, pancreas, spleen, lung, kidney, and mesenteric lymph n~d e~.~x~~.~~,~~,~~,~~ Extragenital occurrence of CTVT without genital lesions has been reported in the nasal cavity,17,20,36,37,46 conjunctiva and eye,'^^,^^ kin,^^,^^ tonsils, buccal muco~a,~O and anal mucosa.6 These atypical locations of CTVT can be due either to a previous regression of the primary genital t~m~r~~,~~ or to implantation of tumor cells on external mucous membranes by licking and ~n i f f i n g .~~.~~ In these atypical cases, it is usually difficult to carry out a differential diagnosis with other canine round cell tumors such as lymphomas, histiocytomas, poorly differentiated mast cell tumors, amelanotic melanomas, and poorly differentiated carcinomas. 15,17,36,46 Although round cell tumors have been immunocharacterized using several tumor markers,2,4J4J9,31,32,43 few immunohistochemical studies on the CTVT have been made so far23,43 and the cell origin and immunophenotype remain Spontaneous regression of CTVT may occur, and recovered dogs can acquire humoral and cellular immunity, which prevents subsequent t~m o r s .~,~~ Some authors have found a significant increase of T lymphocytes infiltrating the tumor masses of spontaneous regressive CTVT. 1,29,45 These lymphocytes were identified using anti-thymocyte sera in fr...

Concise Review: Transmissible Animal Tumors as Models of the Cancer Stem-Cell Process

“…While variation between studies, in terms of laboratory technique and scoring criteria can explain certain differences in the percentage of tumors positive for any specific marker, in each study, for many markers, only a subset of tumors expressed the majority of key markers within the tumor population as a whole (Table 1). In CTVT, for example, Mozos et al found that 40% tumors expressed lysozyme and 56% a-1-antitrypsin, while Marchal et al found that 79% of tumors expressed the macrophage marker ACM1 [15,16]. Similar findings are seen for DFTD.…”

“…CTVT is generally recognized to represent a histiocytic sarcoma affecting primarily the external genitalia, being transmitted to both males and females via cell transfer during coitus [1,3,[15][16][17][18][19]. Extragenital primary sites, as a result of licking or sniffing of lesional tissues include skin, nasal, and orofacial tissues.…”

Brain Metastasis In A Case Of Canine Transmissible Venereal Tumor After A Supposed Successful Treatment With Vincristine Sulfate

“…Expression of lysozyme is normally seen, but in some cases it can be variable or even negative, evidencing a variability of its expression [9].…”

“…Histopathology demonstrate sheets, rows and cords of relatively uniform round to ovoid cells with large nuclei, and a moderate amount of clear cytoplasm with a high mitotic index [7]. Immunohistochemical studies are required for differentiation with other round cell tumours, TVT showing constant immunoreactivity to vimentin, variable positivity to lysozyme and alpha-1-antitrypsine and negative results for cytokeratin, S-100 protein, lambda light chain immunoglobulin, IgG, IgM, CD3 and CD79a antigen [8,9]. TVT is singular in its responsiveness to a variety of treatments [10], chemotherapy with vincristine sulphate being the most effective [11].…”

Clonally transmissible cancers in dogs and Tasmanian devils

“…CTVT cells do not have many distinctive ultrastructural features (Murray et al, 1969;HernandezJauregui et al, 1973;Cockrill and Beasley, 1975;Kennedy et al, 1977;Hill et al, 1984). Owing to its expression of lysozyme, a-1-antitrypsin, NSE and vimentin, CTVT has been proposed to be derived from the macrophage lineage (Table 1; Sandusky et al, 1987;Gimeno et al, 1995;Mozos et al, 1996;Marchal et al, 1997;Mukaratirwa et al, 2004). This diagnosis is supported by the observation that CTVT cells themselves may be parasitized by Leishmania infantum, an organism that normally infects macrophages (Albanese et al, 2002;Catone et al, 2003).…”