THE ANATOMICAL RECORD 300:1009–1010 (2017)
LETTER TO THE EDITOR
Canine Transmissible Venereal
Tumor: Is Its Biological Behavior
Changing?
Canine transmissible venereal tumor (CTVT) is a
sexually transmitted tumor clone that has proliferat-
ed continuously for thousands of years in canine pop-
ulations (Strakova and Murchison, 2014); over the
years, CTVT has been the subject of numerous inves-
tigations. However, many questions regarding its bio-
logical behavior remain unresolved. It is known that
some CTVTs present with varying degrees of aggres-
siveness (Amaral et al., 2011) and resistance to che-
motherapy (Florez et al., 2016). Usually, the more
severe cases result in metastasis and dissemination
of the tumor. This demonstrates the need for specific
treatments for different tumor types, thereby mini-
mizing cost and side effects by avoiding excessive use
of chemotherapy (Gaspar et al., 2010; Florez et al.,
2016). This tumoral behavior has led a group of vet-
erinarian pathologist researchers from the S~ ao Paulo
State University, Brazil (UNESP-Botucatu) to con-
duct several studies, which evidenced the following
common fact: as CTVT becomes more aggressive, the
tumor begins to exhibit changes in its biological
profile. Initially, a cytopathological analysis of the
tumors revealed that CTVT presents different cyto-
morphological types, which are currently classified as
plasmacytoid and lymphocytoid; we hypothesized that
there is a correlation between these cytomorphologi-
cal types and the degree of tumor aggressiveness
(Amaral et al., 2007; Montoya et al., 2012). Subse-
quently, it was established and supported by several
studies that CTVT cases with a higher level of
aggressiveness had tumors consisting of predomi-
nantly plasmacytoid cells (Bassani-Silva et al., 2007;
Gaspar et al., 2010; Amaral et al., 2011). Moreover,
single-cell gel electrophoresis, a visual technique to
analyze and measure DNA breaks in mammalian
cells that is also known as the “comet test”, demon-
strated that CTVT cases with a plasmacytoid mor-
phology exhibited fewer DNA breaks, which is
probably an evasive mechanism for the elimination of
tumor cells (Amaral et al., 2011). Likewise, immuno-
histochemical studies (IHC) performed in CTVT cases
revealed that the plasmacytoid morphology is associ-
ated with both high Ki-67 reactivity (Bassani-Silva
et al., 2015) and an increased expression of P-
Glycoprotein, indicating a higher mitotic potential
C 2016 WILEY PERIODICALS, INC.
V
and resistance to chemotherapy, respectively (Gaspar
et al., 2010; Montoya et al., 2012). In our in vivo
studies, we assessed the expression of P-glycoprotein
in 102 CTVT cases; of these samples, 50% presented
plasmacytoid morphology, 18.63% presented lympho-
cytoid morphology and 31.37% presented mixed mor-
phology. Furthermore, 46 (45%) expressed P-
glycoprotein and 56 (55%) were negative. In addition,
the plasmacytoid group displayed a significantly
greater level of immunoreactivity to the anti-P-
glycoprotein antibody (P < 0.05) compared to the lym-
phocytoid group (Gaspar et al., 2010). In the current
investigations, CTVT cells subjected to vincristine
displayed a high expression level of the (Pgp) MDR-1
gene (Florez et al., 2016), with these tumors requir-
ing more chemotherapeutic applications for regres-
sion or even a modified therapy in some cases
(Gaspar et al., 2010; Florez et al., 2016). In other in
vitro studies, the plasmacytoid pattern of CTVT
showed a higher resistance against propolis action
(Bassani-Silva et al., 2007). Furthermore, these stud-
ies have established that a large percentage of meta-
static CTVTs exhibits a predominantly plasmacytoid
morphology (Gaspar et al., 2010). Therefore, our
study suggests that the plasmacytoid form is a pro-
gressive stage of the lymphocytoid pattern, which
indicates the possibility of progressive modifications
in the biological profile of tumoral cells. Therefore,
the adaptive and continuing evolution of CTVT cells
from a less aggressive lymphocytoid form to a more
aggressive plasmacytoid one is very likely. Despite
this, the question of whether resistance to vincristine
is related to the plasmacytoid cytological phenotype
in CTVT is controversial because research conducted
by other groups found no such association (Lima
et al., 2013; Paranzini et al., 2015). This controversy
may be a function of the need for a better under-
standing of and a detailed utilization of the classifica-
tion system, which does not occur in all cases;
however, both factors, the resistance and aggressive-
ness of CTVT, still require a greater clarification
from a multi-causal perspective, taking into account
the cytological, histopathological, and molecular
aspects, with the aim of determining the degree of
association between the cytological pattern of the
1010 LETTER TO THE EDITOR
tumor and its biological behavior. In conclusion, this
tumoral behavior highlights the need for further
research to contribute not only to the discovery of more
suitable clinical and therapeutic forms to treat patients
with this condition but also the understanding of simi-
lar phenomena affecting animals and humans.
A. P. Duzanski
Laboratory of Investigative and
Comparative Pathology
FMVZ–UNESP
Botucatu, Brazil
Department of Pathology Botucatu Medical School
Universidade Estadual Paulista – UNESP
Botucatu, Brazil
H. B. F^eo
Laboratory of investigative and
Comparative Pathology
FMVZ-UNESP
Veterinary Pathology Research Group
College of Agricultural Sciences
Universidad de Caldas Manizales
Colombia
L. M. Florez*
Laboratory of Investigative and Comparative
Pathology FMVZ–UNESP
Botucatu, Brazil
Veterinary Pathology Research Group
College of Agricultural Sciences
Universidad de Caldas
Manizales, Colombia
C. V. Seullner
Department of Veterinary Surgery
School of Veterinary Medicine and Animal Sciences
Universidade do Estado de S~ao Paulo
Botucatu, Brazil
N. S. Rocha
Laboratory of Investigative and Comparative
Pathology FMVZ–UNESP
Botucatu, Brazil
Veterinary Pathology Research Group
College of Agricultural Sciences
Universidad de Caldas
Manizales, Colombia
LITERATURE CITED
Amaral AS, Bassani-Silva S, Ferreira I, Fonseca LS, Andrade
FHE, Gaspar LFJ, Rocha NS. 2007. Cytomorphological charac-
terization of transmissible canine venereal tumor. Rev Port
Ci^enc Vet 102:253–260.
Amaral AS, Ferreira I, Colodel MM, Salvadore DMF, Rocha NS.
2011. DNA damage in canine transmissible venereal tumour.
Rev Lus ofona Ci^en Med Vet 4:1–5.
Bassani-Silva S, Fl orez LM, Ballestero HF, Rocha NS. 2015.
Imuno-express~ ao de Cox-2, Caspase 3, Ki67 e Survivin em
tumor ven ereo transmissıvel canino. Rev Vet Zootec 22:275–
287.
Bassani-Silva S, Sforcin JM, Amaral AS, Gaspar LFJ, Rocha
NS. 2007. Propolis effect in vitro on canine transmissible vene-
real tumor cells. Rev Port Ci^enc Vet 102:261–265.
Florez MM, Feo H, Yamatogi R, Pessoa J, Da Silva G, Araujo J,
Rocha N. 2016. Cell cycle kinetics, apoptosis rates and gene
expressions of MDR-1, TP53, Bcl-2 and BAX in transmissible
venereal tumor cells and their association with therapy
response. Vet Comp Oncol 14:1–15.
Gaspar LF, Ferreira I, Colodel MM, Brand~ ao CVS, Rocha NS.
2010. Spontaneous canine transmissible venereal tumour: cell
morphology and influence on p-glycoprotein expression. Turk
J Vet Anim Sci 34:447–454.
Lima CRO, Rabelo RE, Vulcani VAS, FAP, Helrigel PA, Brito
LAB, Moura VMBD. 2013. Morphological patterns and malig-
nancy criteria of transmissible venereal tumor in cytopatho-
logical and histopathological exams. Braz J Vet Res Anim Sci
50:238–246.
Montoya MF, Pedraza FJ, Grandi F, Rocha NS. 2012. Cytologic
subtypes of canine transmissible venereal tumor. Vet Clin
Pathol 41:4–5.
Paranzini CS, Sant’anna MC, Di Santis GW, Martins MIM.
2015. Prevalence of different cytomorphological types of trans-
missible venereal tumours and the association with prognosis
in dogs treated with vincristine sulphate—retrospective study.
Semina: Ci^ enc Agr 36:3795–3800.
Strakova A, Murchison EP. 2014. The changing global distribu-
tion and prevalence of canine transmissible venereal tumour.
BMC Vet Res 10:168.
Conflict of interest: The authors declared that they have
no potential conflicts of interest with respect to the author-
ship and/or publication of this article.
*Correspondence to: L. M. Montoya, Laboratory of Investi-
gative and Comparative Pathology, FMVZ–UNESP, Botu-
catu, Brazil. E-mail: maomontoya53@yahoo.es
Received 16 May 2016 Accepted: 5 October 2016.
DOI 10.1002/ar.23527
Published online 16 December 2016 in Wiley Online Library
(wileyonlinelibrary. com).