In dogs, ASACA is an aggressive malignancy with reported metastatic rates that range from 46% to 96%.1–4 Generally, metastasis initially develops in the lymph nodes that drain the sublumbar region and then progresses cranially over time to the spleen, liver, lungs, and other organs.1–5 Approximately 25% of dogs with ASACA develop paraneoplastic hypercalcemia, which has a negative effect on prognosis.6 Results of some studies6,7 suggest that dogs in which ASACA is diagnosed during the early stages of the disease have a better prognosis than dogs in which the disease is diagnosed during its later stages; however, those studies included dogs treated with both local and systemic therapies. The metastatic rate and survival time for dogs with early-stage ASACA following surgical treatment alone are unknown, and the value of adjuvant therapy in those dogs is also unclear.
Tumor size is associated with outcome for dogs with ASACA.6,7 In 1 study,6 the median survival time was 584 days for dogs with tumors < 10 cm2, compared with 292 days for dogs with tumors ≥ 10 cm2; however, dogs with metastatic disease at the time of surgery were not excluded from that analysis, and treatment regimens varied among dogs. Investigators of another study7 also reported that tumor size was negatively associated with survival time and advocated use of a staging system in which a cutoff of 2.5 cm in diameter for a primary tumor was a central determinant in a patient management algorithm.
The effect of lymph node metastasis on prognosis for dogs with ASACA is less clear. In 1 study,6 the median survival time did not differ between dogs with and without iliac lymphadenopathy, but those findings were likely confounded by the fact that dogs with lymphadenopathy were more likely to receive chemotherapy than dogs without lymphadenopathy. In another study,7 lymph node metastasis had a significant negative effect on survival time, and the investigators of that study proposed a staging system in which nodal metastasis was categorized as absent, present with lymph nodes < 4.5 cm in diameter, or present with lymph nodes > 4.5 cm in diameter. In that study,7 the median survival time for dogs with primary tumors < 2.5 cm in diameter and no lymph node metastasis was 1,205 days. In yet another study,8 there was a significant negative association between lymph node metastasis and outcome for dogs with ASACA. However, all 3 studies6–8 were limited by the fact that treatment regimens were not standardized and varied among individual dogs.
Histologic and immunohistochemical characteristics have also been evaluated as prognostic indicators of tumor behavior and outcome in dogs with ASACA. In 1 study,9 the risk of ASACA-related death was greater for dogs with tumors with a solid or partly solid histologic pattern than for dogs with tumors with rosette or tubular-type patterns. Ki-67, a nuclear marker of cellular proliferation, was identified in ASACA tumor cells for a proportion of the dogs of that study,9 but its association with clinical or outcome data was not evaluated. In another study,10 abnormally decreased expression of E-cadherin, a transmembrane protein that mediates cell-cell and cell-matrix interactions, was associated with a poor prognosis for dogs with various stages of ASACA that received various treatments. To our knowledge, the relationship between specific cellular proliferation indices and the clinical behavior or outcome for dogs with ASACA has not been evaluated.
Although previous studies6–10 have described outcome and prognostic factors for dogs with ASACA, none have controlled for stage of the disease at the time of diagnosis or treatment. The purpose of the study reported here was to determine the survival time and tumor recurrence and metastatic rates for dogs with early-stage ASACA that were treated with surgery alone and assess whether specific clinical, pathological, or immunohistochemical factors were predictive of outcome for that population.
This study was not supported by a grant. The authors declare that there were no conflicts of interest.
Presented in abstract form at the annual meeting of the Veterinary Cancer Society, St Louis, October 2014.
The authors thank Kurt Takahashi, Christopher Kwong, Felicia DonRussello, and Michael Manzer for technical assistance.
Anal sac adenocarcinoma
Time to progression
Target Retrieval Solution S1699, Dako North America Inc, Carpinteria, Calif.
Ki-67 antigen (clone MB-1), Dako North America Inc, Carpinteria, Calif.
Purified mouse anti–E-cadherin (clone 36), BD Biosciences, San Jose, Calif.
4+ Detection System, Biocare Medical, Concord, Calif.
NovaRED for peroxidase (SK-4800), Vector Laboratories, Burlingame, Calif.
Prism, version 6.0c, GraphPad Software Inc, La Jolla, Calif.
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