Prognostic Value of Ki67 and Other Clinical and Histopathological Factors in Canine Apocrine Gland Anal Sac Adenocarcinoma

Abstract

Apocrine gland anal sac adenocarcinoma (AGASACA) is locally aggressive and highly metastatic to regional lymph nodes. The aim of this study was to evaluate the prognostic significance of Ki67 in surgically excised AGASACA. Prognostic impact of size, regional lymph nodes metastasis, hypercalcemia, histologic pattern, mitotic count, necrosis, inflammatory and lympho-vascular invasion, anisokaryosis and anisocytosis was also evaluated. Thirty-five dogs were included, twenty-four of which also had metastatic lymph nodes. When the entire population was evaluated, only metastatic disease spread to regional lymph nodes, and necrosis and inflammatory infiltration were correlated to prognosis. When only dogs with metastatic disease were evaluated, size, solid histologic pattern, presence of lymphatic and vascular invasion showed influence on prognosis. Ki67 index was not associated with survival time and disease free interval in any case. The results of this study showed that lymph nodes metastasis at diagnosis reduced disease free interval. Moreover, tumor size greater than 5.25 cm, presence of lymphatic and vascular invasion and a solid histologic pattern were associated with a shorter survival time in dogs with metastasis to regional lymph nodes. Ki67 expression was not significantly associated with prognosis, therefore it could not be considered as a prognostic factor in this tumor type, while the role of hypercalcemia remained unclear.

A Retrospective Study of Clinical and Histopathological Features of 81 Cases of Canine Apocrine Gland Adenocarcinoma of the Anal Sac: Independent Clinical and Histopathological Risk Factors Associated with Outcome

“…Confirming our hypothesis, the algorithm was able to stratify cases into two groups with a significantly different MST and hazard ratio. Using the methodology applied here, Ki67% was not found to be useful in predicting overall survival, a finding consistent with studies [ 17 , 30 ]. Furthermore, Ki67% and the mitotic count showed no correlation in our data.…”

“…A solid histological pattern has previously been found to correlate with poor survival on univariate analysis. [ 11 , 16 , 30 ] Our findings support the hypothesis that loss of the original glandular tissue architecture suggests a loss of cellular differentiation and a more aggressive biological behaviour. Previous evidence also supports an association between decreased survival and the presence of necrosis or vascular invasion [ 16 , 30 ].…”

“…[ 11 , 16 , 30 ] Our findings support the hypothesis that loss of the original glandular tissue architecture suggests a loss of cellular differentiation and a more aggressive biological behaviour. Previous evidence also supports an association between decreased survival and the presence of necrosis or vascular invasion [ 16 , 30 ]. We evaluated our hypothesis that two or more of these factors was a more discriminating threshold to differentiate between less favourable and favourable survival times.…”

“…Studies investigating clinical factors as indicators of PFI are less numerous; however, tumour size, lymph node metastasis [ 15 ], sublumbar lymphadenopathy [ 19 ], and hypercalcaemia [ 29 ] have been associated with a decrease in median PFI (MPFI). The histological variables of necrosis, solid tumour pattern, vascular invasion and peripheral infiltration, when considered in isolation, have been associated with decreased overall survival [ 11 , 16 , 30 ]. Previous studies have found no association between mitotic count and survival and/or metastasis at presentation [ 16 , 31 ].…”

“…Previous studies have found no association between mitotic count and survival and/or metastasis at presentation [ 16 , 31 ]. The role of the proliferation marker Ki67 in predicting the progression of AGASAC cases has not been clearly defined; however, studies so far have found no association between per cent of Ki67 immunolabelling within the primary tumour and metastatic lymph nodes with overall median survival time (MST) [ 17 , 30 ].…”