Expression of Cyclooxygenase-2 and Ki-67 in Actinic Keratosis and Cutaneous Squamous Cell Carcinoma in Dogs

Abstract

Actinic keratosis is a common disease in humans, which also affects dogs. Lesions occur in chronically sun exposed areas, such as flank, ventral and lateral abdomen. It has been reported that actinic keratosis is a pre-neoplastic disease which may evolve into squamous cell carcinoma (SCC), which is one of the most frequent malignant neoplasm in dogs. The aim of this research was to investigate the relationship between COX-2 and cell proliferation on the outcome of dogs with actinic keratosis and cutaneous squamous cell carcinoma. This study included 10 skin sections of actinic keratosis (G1) and 10 cutaneous SCC (G2). Data including age, breed, gender and histopathological findings were documented. Paraffin-embedded tissues were retrieved for COX-2 and Ki-67 staining. American Pit Bull Terrier dogs were the most affected ones in both G1 and G2, the mean age was 4.3 (±0.8) years and 5.6 (±1.7) years, respectively. Mean score of COX-2 immunostaining in G1 and G2 was 8.16 (±3.51) and 8.56 (±1.03), respectively. Mean percentage of immunopositive cells for Ki-67 in G1 and G2 was 15.77 (±8.81) and 17.71 (±12.21), respectively. There was no association between COX-2 expression and Ki-67, recurrence, survival and metastasis rate (p > 0.05). These findings highlight the role of COX-2 and Ki-67 in carcinogenesis, but do not confirm the relationship between COX-2 expression and increased cell proliferation in dogs. COX-2 may play a role in carcinogenesis, but this pathway is not responsible for cellular proliferation in actinic keratosis and cutaneous SCC in dogs. Both markers were not useful tools to differentiate the outcome of affected dogs.

Electrochemotherapy with bleomycin associated with doxorubicin induces tumor regression and decreases the proliferative index in canine cutaneous squamous cell carcinomas

“…Because ECT is a recent technique in Veterinary Medicine, a limited number of studies have demonstrated the ECT antitumoral effect in cSCC. In general, the high expression level of Ki67 observed in SCC, especially in poorly differentiated SCC, is related to an aggressive potential [9,34,37,49]. However, in the lesions studied, the proliferation index could also be considered high despite the predominance of well-differentiated SCC (83.3%), suggesting the aggressive potential, despite the degree of differentiation.…”

“…cSCC is the second most common cutaneous tumor in dogs [5], with an incidence between 3-20% [6,7]; however, the incidence of cSCC depends on the geographic area [5]. In humans and dogs, actinic keratosis is an SCC precursor lesion with more than 80% of the SCC cases in humans being derived from previous actinic keratosis [8, 9].…”

Clinical outcome and cyclo‐oxygenase‐2 expression in five dogs with solar dermatitis/actinic keratosis treated with firocoxib

“…Poor owner compliance with respect to the use of protective sun solar suits before and during the study period would encourage the use of firocoxib as a chemopreventive in solar dermatitis. The rationale for the use of firocoxib in this study is related to the recent demonstration of COX‐2 expression in dogs and cats with squamous cell carcinoma and actinic keratosis . Skin biopsies pretreatment in all five dogs showed COX‐2 immunostaining in the keratinocytes and served as comparison for the assessment of immunostaining in the same dogs during and after firocoxib treatment.…”

“…The conversion of arachidonic acid into prostaglandin is catalysed by the cyclo‐oxygenases (COX); human and laboratory animal studies indicate that COX‐2 is overexpressed in actinic keratosis and squamous cell carcinoma . More recently, COX‐2 expression has been shown in canine and feline actinic keratosis and squamous cell carcinoma …”

Estudo comparativo dos aspectos clínicos, morfológicos e moleculares da ceratose actínica e do carcinoma de células escamosas na pele da região ventral abdominal de caninos domésticos

“…Em nosso estudo, a raça mais acometida foi a American PitBull Terrier, condizendo com a literatura (North;Banks, 2009;Costa, 2009;Vail;Withrow, 2007;Poggiani et al, 2012). As regiões anatômicas mais acometidas pela doença são locais com menor cobertura de pelos, como face interna de membros, plano nasal, pina de orelhas e abdome como descrito em nosso estudo (Almeida et al, 2001, Carvalho, 2008Milanta et al, 2016).…”