Cell Carcinoma In Dog Research Articles

P63 and E-cadherin Expression in Canine Oral Squamous Cell Carcinoma.

The expression of p63 and E-cadherin was studied in 22 oral squamous cell carcinomas in the dog according to immunohistochemical techniques. The association between these markers and clinicopathologic parameters was assessed. All tumor cells studied showed enhanced p63 expression. Regarding E-cadherin expression, 17 of 22 cases (77.3%) showed decreased immunoreactivity, and in 13 of 22 cases (59.1%), its expression was cytoplasmic. Neither p63 nor E-cadherin expression patterns were associated with tumor size, bone invasion, or lymph node metastasis. p63 score was related to proliferating cell nuclear antigen proliferative index (P = .020). A statistically significant correlation between the expression patterns of these 2 markers was noted (P = .026). Furthermore, they were related with tumor grade. An atypical p63 labeling and a cytoplasmic E-cadherin staining were statistically related with a higher tumor grade (P = .022 and P = .017, respectively). These findings suggest that changes in p63 and E-cadherin expression are frequent events in oral squamous cell carcinoma in dogs.

Early stage of cutaneous squamous cell carcinoma in dog

A four year old Labrador dog with small grayish white rapidly growing mass was presented. Biopsy of growth yielded anaplastic squamous cells. Microscopic examination of excised tumor tissue revealed anaplastic, proliferating squamous cells invading dermis and forming numerous epithelial nests and keratin depositions in the centre. The profile of growth was confirmative of early stage of squamous cell carcinoma (SCC).

Digital Squamous Cell Carcinoma in Dogs

Squamous cell carcinoma represents 47.4% of all malignant canine digital lesions, but despite its frequency, there are few published studies available. Pathology submission records of 154 cases and follow-up of 49 animals were analyzed. On the 49 cases, histological evaluation was performed of the differentiation degree, mitotic index, presence of emboli, and immunohistochemical expression of vimentin and E-cadherin. The mean (SD) age of affected animals was 10.2 (2.3) years; no sex predisposition was recorded. Beauceron and Briard were 2 new overrepresented breeds. Dark-haired animals comprised 97 of 105 (92%); 94 dogs of 125 (75.2%) belonged to large and giant breeds. The forelimb was affected twice more than the hind limb. Probable metastases were observed in 4 dogs; new tumor development was recorded in 11 of 49 (22.4%). Epidemiologic factors, histological grade, mitotic index, and expression of immunohistochemical markers seemed not to be related to the clinical outcome.

Clinical, Histologic, and Computed Tomographic Features of Oral Papillary Squamous Cell Carcinoma in Dogs: 9 Cases (2008–2011)

Medical records of dogs diagnosed with oral papillary squamous cell carcinoma between December 2008 and April 2011 were reviewed. Information abstracted included signalment, tumor location, tumor size, computed tomographic (CT) features, evidence of metastatic disease based on cytologic examination of lymph node aspirates and thoracic radiography, treatment, surgical margins, histologic features, and treatment outcome. Dogs included in the study were all sexually altered, predominantly large breed dogs with a mean age of 3.9-years (range, 0.5 to 9.0-years). The most common location was the rostral maxilla. Invasion of underlying bone and lymphadenopathy were evident on CT imaging in most dogs. No evidence of metastasis was found on mandibular lymph node cytology and thoracic radiography. Histologic analysis revealed similar morphologic findings for all surgically resected tumors. Surgical excision with 1-2 cm margins was complete in all cases, with a mean tumor-free interval of 12.1-months.

Retrospective evaluation of doxorubicin–piroxicam combination for the treatment of transitional cell carcinoma in dogs

To determine whether doxorubicin-piroxicam combination is safe and has activity against transitional cell carcinoma in dogs. Data was collected retrospectively from 34 dogs from two institutions over a 6-year period. Signalment, clinical presentation, treatment specifics, adverse events, response, progression-free survival and overall survival time were evaluated. Dogs received doxorubicin every 3 weeks and daily piroxicam; 17 dogs (50%) had surgery. Clinical presentations were those typically reported for transitional cell carcinoma. Mean number of doses administered was 3·5. Of the 23 dogs with measurable disease, 14 (60·5%) had stable disease, 7 (30·5%) had progressive disease and 2 (9%) a partial response. Adverse events were generally manageable, and gastrointestinal in origin; one dog died of treatment-related complications. Overall median progression-free survival and overall survival were 103 and 168 days, respectively. Cytoreductive surgery did not result in prolongation of progression-free survival, but significantly prolonged overall survival. All dogs but one died as a result of disease progression. Doxorubicin-piroxicam combination therapy is well-tolerated in dogs with transitional cell carcinoma although progression-free survival, overall survival and biological response rates appear modest. Combination with surgery appears to offer a survival advantage; however, this may reflect tumour location and volume. Prospective studies are necessary to compare activity of combination doxorubicin-piroxicam to currently applied therapies.

Outcome of urethral stent placement for management of urethral obstruction secondary to transitional cell carcinoma in dogs: 19 cases (2007–2010)

To determine the outcome in dogs undergoing urethral stent placement for management of urethral obstruction secondary to transitional cell carcinoma (TCC). Retrospective case series. 19 dogs with histopathologically confirmed TCC. Information regarding urethral stent placement and follow-up treatment was obtained from review of medical records. Quality of life assessment was performed with an owner questionnaire. Self-expanding nitinol stents were successfully placed in 17 of 19 dogs; stent placement was not possible in one dog, and another dog was euthanatized 2 days after stent placement, but before discharge from the hospital. Median survival time in 17 dogs following successful long-term stent placement was 78 days (range, 2 to 366 days). Complications following stent placement in 18 dogs included incontinence (n = 7), reobstruction from continued growth of urethral TCC (3), acute reobstruction shortly after the procedure (1), and stent migration (2). Of the 17 owners surveyed, 16 were satisfied with the outcome and would recommend urethral stent placement. The placement of self-expanding nitinol urethral stents was successful in alleviating TCC-induced urethral obstruction and providing good quality of life for most dogs.

Histological Subtypes of Oral Non-tonsillar Squamous Cell Carcinoma in Dogs

Several histological subtypes and grades of oral squamous cell carcinoma (SCC) are described in human literature and these subtypes have distinct morphological features and biological behaviour. This retrospective study (1990-2010) included 84 dogs diagnosed with SCC of the oral cavity and oropharynx, excluding the tonsils. Sixty-nine of the SCCs (82.1%) were further diagnosed as conventional SCC (CSCC) (33 [47.8%] well-differentiated, 31 [44.9%] moderately-differentiated and five [7.3%] poorly-differentiated), five (5.95%) each as papillary SCC and basaloid SCC, three (3.6%) as adenosquamous carcinoma and two (2.4%) as spindle cell carcinoma. Compared with the general hospital population, neutered female dogs, dogs aged 10 to <15 years, English springer spaniels and Shetland sheepdogs were overrepresented. The majority (78.1%) of SCCs were proliferative with or without associated ulceration, although no significant association was observed between the gross appearance and different SCC subtypes. 71.4% of SCCs were located in dentate jaws; however, well-differentiated CSCC more often affected the tongue and other non-dentate mucosal surfaces (P=0.0022). No significant association was found between any of the SCC subtypes and tumour-associated inflammation (TAI), perineural and lymphovascular invasion (PNI, LVI), or between gross appearance of the tumour and tumour location, PNI, LVI or TAI or PNI, LVI, TAI and tumour location.

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

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.

Cyclooxygenase-2 Expression in Animal Cancers

Cyclooxygenase (COX; also known as prostaglandin endoperoxide synthase) is a key enzyme in the biochemical pathway leading to the synthesis of prostaglandins. A large amount of epidemiological and experimental evidence supports a role for COX-2, the inducible form of the enzyme, in human tumorigenesis, notably in colorectal cancer. COX-2 mediates this role through the production of PGE(2) that acts to inhibit apoptosis, promote cell proliferation, stimulate angiogenesis, and decrease immunity. Similarly, COX-2 is believed to be involved in the oncogenesis of some cancers in domestic animals. Here, the author reviews the current knowledge on COX-2 expression and role in cancers of dogs, cats, and horses. Data indicate that COX-2 upregulation is present in many animal cancers, but there is presently not enough information to clearly define the prognostic significance of COX-2 expression. To date, only few reports document an association between COX-2 expression and survival, notably in canine mammary cancers and osteosarcomas. Some evidence suggests that COX inhibitors could be useful in the prevention and/or treatment of certain cancers in domestic animals, the best example being urinary transitional cell carcinomas in dogs. However, determination of the levels of COX-2 in a tumor does not appear to be a good prognostic factor or a good indicator for the response to nonsteroidal anti-inflammatory drug therapy. Clearly, additional research, including the development of in vitro cell systems, is needed to determine if COX-2 expression can be used as a reliable prognostic factor and as a definite therapeutic target in animal cancers.

Assessment of changes in vascularity and blood volume in canine sarcomas and squamous cell carcinomas during fractionated radiation therapy using quantified contrast-enhanced power Doppler ultrasonography: A preliminary study

Radiation therapy does not only target tumour cells but also affects tumour vascularity. In the present study, changes in tumour vascularity and blood volume were investigated in five grade 1 oral fibrosarcomas, eight other sarcomas (non-oral soft tissue and bone sarcomas) and 12 squamous cell carcinomas in dogs during fractionated radiation therapy (total dose, 45-56 Gy). Contrast-enhanced power Doppler ultrasound was performed before fraction 1, 3, 6, 8, 10, 12, 14 and 15 or 16 (sarcomas) or 17 (squamous cell carcinomas). Prior to treatment, median vascularity and blood volume were significantly higher in squamous cell carcinomas (P=0.0005 and 0.001), whereas measurements did not differ between oral fibrosarcomas and other sarcomas (P=0.88 and 0.999). During the course of radiation therapy, only small, non-significant changes in vascularity and blood volume were observed in all three tumour histology groups (P=0.08 and P=0.213), whereas median tumour volume significantly decreased until the end of treatment (P=0.04 for fibrosarcomas and other sarcomas, P=0.008 for squamous cell carcinomas). It appeared that there was a proportional decrease in tumour volume, vascularity and blood volume. Doppler measurements did not predict progression free interval or survival in any of the three tumour groups (P=0.06-0.86). However, the number of tumours investigated was small and therefore, the results can only be considered preliminary.

Superficial keratectomy and topical mitomycin C as therapy for a corneal squamous cell carcinoma in a dog

A 10-year-old female West Highland white terrier was presented with refractory hyperplastic keratitis of the left cornea of one month's duration. At this time, a vascularised and rough lesion 5 mm in diameter was observed on the left cornea. No other abnormality was recognised on the affected eye. The corneal neoplasm was surgically removed and histologically diagnosed as a squamous cell carcinoma. For two months after the surgery, 0.04 percent mitomycin C (MMC) eye drops were applied as adjuvant chemotherapy. Primary corneal squamous cell carcinoma with no history of keratoconjunctivitis sicca is rare in dogs. In the present report, surgical removal of the neoplasm was combined with the topical administration of the anticancer drug mitomycin C and a good prognosis was obtained. The result indicates that the combination treatment used in this case may be an appropriate therapeutic choice for corneal squamous cell carcinoma in dogs.

Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs.

To determine the maximum tolerated dose (MTD) of cisplatin administered with piroxicam, the antitumor activity and toxicity of cisplatin combined with piroxicam in dogs with oral malignant melanoma (OMM) and oral squamous cell carcinoma (SCC), and the effects of piroxicam on the pharmacokinetics of cisplatin in dogs with tumors. Prospective nonrandomized clinical trial. 25 dogs. Dogs were treated with a combination of cisplatin (escalating dose with 6 hours of diuresis with saline [0.9% NaCI] solution) and piroxicam (0.3 mg/kg 10.14 mg/lb], PO, q 24 h). The initial cisplatin dose (50 mg/m2) was increased by 5 mg/m2 until the MTD was reached. Tumor stage and size were determined at 6-week intervals during treatment. The pharmacokinetics of cisplatin were determined in dogs receiving a combination of cisplatin and piroxicam during the clinical trial and dogs that were treated with cisplatin alone. 11 dogs with OMM and 9 dogs with SCC were included in the clinical trial. The MTD of cisplatin when administered in combination with piroxicam was 50 mg/m2. Tumor remission occurred in 5 of 9 dogs with SCC and 2 of 11 dogs with OMM. The most common abnormality observed was renal toxicosis. Clearance of cisplatin in dogs that were treated with cisplatin alone was not significantly different from that in dogs treated with a combination of cisplatin and piroxicam. Cisplatin administered in combination with piroxicam had antitumor activity against OMM and SCC. The level of toxicity was acceptable, although renal function must be monitored carefully.

Expression of cyclo-oxygenase-2 in naturally occurring squamous cell carcinomas in dogs.

Squamous cell carcinoma is one of the most common cancers in humans and is also a frequently diagnosed neoplasm in dogs. Induction of cyclo-oxygenase-2 (COX-2), a key rate-limiting enzyme in prostaglandin biosynthesis, has been implicated in the oncogenesis of various cancers in humans, including squamous cell carcinomas. However, expression of COX-2 has not been reported in spontaneous squamous cell carcinomas of non-human species. Canine squamous cell carcinomas share several similarities with the human disease. Therefore, the objective of this study was to determine whether COX isoenzymes were expressed in naturally occurring cases of squamous cell carcinomas in dogs. Canine normal skin (n=4) and squamous cell carcinomas (n=40) were studied by immunohistochemistry and immunoblotting analysis using polyclonal antibodies selective for COX-1 or COX-2. COX-2 was strongly expressed by neoplastic keratinocytes in all cases of squamous cell carcinomas, whereas no COX-2 was detected in normal skin and in the non-neoplastic skin and oral mucosa included in the tumor tissue samples (p<0.01). Immunoblotting analysis confirmed the restricted expression of COX-2 (72,000--74,000 molecular weight doublet) in squamous cell carcinomas only. In contrast, faint COX-1 staining was found in normal skin and in squamous cell carcinomas. This study demonstrates for the first time that COX-2 is induced in canine squamous cell carcinomas, and provides a new model to investigate the role and regulation of COX-2 gene expression in naturally occurring squamous cell carcinomas. (J Histochem Cytochem 49:867-875, 2001)

Evaluation of piroxicam for the treatment of oral squamous cell carcinoma in dogs.

To evaluate the use of piroxicam for the treatment of oral squamous cell carcinoma in dogs. Prospective case series. 17 dogs with measurable oral squamous cell carcinoma. Dogs were treated with piroxicam at a dosage of 0.3 mg/kg (0.14 mg/lb) of body weight, PO, every 24 hours until progressive disease or unacceptable signs of toxicosis developed or the dog died. One dog had a complete remission (maxillary tumor), and 2 dogs had partial remissions (lingual tumor and tonsillar tumor). An additional 5 dogs had stable disease, including 1 with a maxillary tumor, 2 with mandibular tumors, and 2 with tonsillar tumors. Variables associated with tumor response were not identified. Median and mean times to failure for the 3 dogs that had a remission were 180 and 223 days, respectively. Median and mean times to failure for the 5 dogs with stable disease were 102 and 223 days, respectively. Time to failure was positively associated with tumor response and negatively associated with tumor size. One dog had mild adverse gastrointestinal tract effects that resolved with the addition of misoprostol to the treatment regimen. Results suggest that piroxicam may be useful in the treatment of dogs with oral squamous cell carcinoma; response rate was similar to that reported for other cytotoxic treatments. Larger-scale studies are warranted to determine what role piroxicam may have, alone or in combination with other treatments, for the treatment of dogs with oral squamous cell carcinoma.

Cisplatin treatment of transitional cell carcinoma of the urinary bladder in dogs: 18 cases (1983–1993)

Objective To determine whether cisplatin administered at a dosage of 60 mg/m2 of body surface area, IV, every 21 days, would induce remission of transitional cell carcinoma of the urinary bladder in dogs. Design Retrospective analysis of medical records. Animals 18 dogs with histologically confirmed transitional cell carcinoma of the urinary bladder. Procedure Clinical staging was performed by means of physical examination, contrast cystography or ultrasonography, and thoracic radiography prior to and 42 days after the initiation of cisplatin treatment. Dogs with clinical signs of tumor progression were reevaluated earlier than 42 days in some instances. Complete remission (CR) was defined as complete resolution of measurable tumor. Partial remission (PR) was defined as a ≥ 50% reduction in tumor volume without development of new tumors. Stable disease was defined as &lt; 50% change in tumor volume at 42 days without development of new lesions. Progressive disease (PD) was defined as ≥ 50% increase in tumor volume or development of new tumors at any time. Dogs were reevaluated at 42-day intervals until they had a CR, developed PD, or developed unacceptable adverse effects. Results Three dogs had a PR, 4 had stable disease, and 9 had PD. Tumor response could not be assessed in 2 dogs: 1 dog developed grand mal seizures 3 hours after the first dose of cisplatin was given and was euthanatized; the other dog continued to have clinical signs of urinary tract obstruction and was euthanatized 8 days after the first dose of cisplatin. Four dogs developed renal azotemia that was suspected to be secondary to cisplatin nephrotoxicity. Clinical Implications The cisplatin dosage was higher than that reported in studies of dogs with transitional cell carcinoma of the bladder. Even with this higher dosage, none of the dogs had a CR, and only 3 of 18 had a PR. A more effective, less toxic treatment for transitional cell carcinoma in dogs is needed. (J Am Vet Med Assoc 1996;209:1588–1591)

Spontaneous squamous cell carcinomas of the oral region in domestic animals: a review and consideration of their relevance to human research.

Spontaneous squamous cell carcinomas of the oral region in domestic animals have the potential of providing additional information about the pathology of oral cancer and may be useful in therapeutic research. Moreover, they exhibit definite advantages over chemically induced tumors in rodents. This article provides background information on spontaneous oral squamous cell carcinomas in dogs, cats, cattle, horses and sheep and then discusses the use in research of such tumors in dogs and cats. These two species are potentially the most useful because they are numerous, suffer quite commonly from squamous cell carcinoma of the oral cavity and oropharynx, and are usually allowed to live approximately normal life spans. Moreover, they are being treated routinely in veterinary hospitals.

RADIOTHERAPY OF CANINE NON‐TONSILLAR SQUAMOUS CELL CARCINOMA

The records of 14 dogs treated with megavoltage radiation for non‐tonsillar oral squamous cell carcinoma were reviewed to determine the efficacy of this treatment modality. Total radiation dose was either 48 or 57 Gray (Gy), while dose per fraction was either 3.0 or 4.0 Gy. Median disease free interval and survival were 365 and 450 days, respectively. Median disease free interval was shorter in dogs older than nine years (210 days) as compared with dogs less than or equal to nine years old (470 days), (p &lt; .005). Median survival was shorter in dogs older than nine years (315 days) as compared with dogs less than or equal to nine years old (1080 days), (p &lt; 0.02). Weight, stage, anatomic subsite, intraoral location, duration of disease, prior surgery, and number of radiation fractions did not appear to influence disease free interval or survival. Data presented herein suggest that survival in dogs with non‐tonsillar squamous cell carcinoma receiving megavoltage radiation may be longer than that achieved with orthovoltage radiation or surgery. Megavoltage radiation appears to be an effective treatment for non‐tonsillar oral squamous cell carcinoma in dogs. Further study is needed to determine the optimal time‐dose sched‐ule.

Treatment by digital amputation of subungual squamous cell carcinoma in dogs: 21 cases (1987-1988)

Summary Malignant digital tumors were diagnosed in 62 dogs during a 1-year period. Twenty-one (33.9%) of the dogs had subungual squamous cell carcinoma. Each of these dogs had involvement of single digits. Sixteen (76.2%) of the dogs with squamous cell carcinoma were large-breed dogs, and 15 (71.4%) had predominantly black coats. Labrador Retrievers (n = 5,23.8%) and Standard Poodles (n = 3,14.3%) were the most commonly represented purebreeds. None of the dogs had evidence of metastases prior to treatment. All 21 tumors were treated by amputation of the involved digit. Histologic evidence of neoplastic bone invasion was found in 15 of the 21 amputated digits (71.4%). Local tumor recurrences were not observed. Only 1 dog developed documented metastatic disease; this dog was euthanatized because of pulmonary metastases 5 months after surgery. At the time of this report, 9 dogs (42.9%) were alive with no evidence of disease (median, 26 months after surgery), and 11 dogs (52.4%) had died or were euthanatized (median, 20 months after surgery). The cause of death in 7 dogs was known to be unrelated to squamous cell carcinoma, and the cause of death in 4 dogs was unknown. The 1-year and 2-year survival rates were 76.2% and 42.9%, respectively.

Ultraviolet Radiation, Solar Dermatosis, and Cutaneous Neoplasia in Beagle Dogs

Beagle dogs that were part of a life span study of the effects of low-level ionizing radiation during development were evaluated for the incidence of skin neoplasia and solar dermatosis. A total of 991 dogs up to 14 years of age were examined. The dogs were housed in gravel-based, outdoor pens with doghouses in a high-altitude, high-sunshine level environment. Solar dermatosis was restricted to the sparsely haired, nonpigmented abdominal skin. Skin neoplasms were either removed surgically or found at necropsy. Solar dermatosis was diagnosed in 363 of the 991 dogs, an incidence of 36.6%. There were 175 hemangiomas, hemangiosarcomas, or squamous cell carcinomas of the skin in the 991 dogs. Of these, 129 tumors occurred in dogs with, and only 46 in dogs without, solar dermatosis. Of the dogs with solar dermatosis, 93 (26%) had at least one of the three tumor types, compared to only 44 (7%) of dogs without solar dermatosis. Thirty-two dogs had multiple tumor types and solar dermatosis, compared to only two dogs with multiple tumor types and no solar dermatosis. There was a highly significant correlation (P less than 0.001) between the occurrence of these tumor types and solar dermatosis in the unpigmented abdominal skin. This correlation was strongest for the malignant neoplasms. Whole-body gamma-radiation exposures were delivered at one of three prenatal or three postnatal ages up to 1 year of age. There appeared to be an increased risk for hemangiosarcomas and squamous cell carcinomas in dogs with solar dermatosis and given gamma-ray exposures at 1 year of age. This suggests an interaction between exposures to ionizing and ultraviolet radiation.

Chemotherapy versus chemotherapy plus radiotherapy in the treatment of tonsillar squamous cell carcinoma in the dog.

The effect of adjuvant chemotherapy and combined chemotherapy and radiotherapy in 22 dogs with advanced canine tonsillar carcinoma (World Health Organization [WHO], T2-3 primary tumor with infiltration into surrounding tissues) was evaluated. There were four treatment groups of at least five dogs each. Combinations of chemotherapeutic drugs reported to have activity against squamous cell carcinoma in humans and dogs (doxorubicin, cisplatin, vinblastine, and cyclophosphamide) were administered after tonsillectomy. Radiation therapy (orthovoltage type, external beam) was combined with chemotherapy in one treatment group. The dogs that had combination radiation therapy and chemotherapy had higher response rates and significantly longer survival times. However, most dogs died of progression of disease.