Molecular assays are widely used to prognosticate canine cutaneous mast cell tumors (MCT). There is limited information about these prognostic assays used on MCT that arise in the subcutis. The aims of this study were to evaluate the utility of KIT immunohistochemical labeling pattern, c-KIT mutational status (presence of internal tandem duplications in exon 11), and proliferation markers-including mitotic index, Ki67, and argyrophilic nucleolar organizing regions (AgNOR)-as independent prognostic markers for local recurrence and/or metastasis in canine subcutaneous MCT. A case-control design was used to analyze 60 subcutaneous MCT from 60 dogs, consisting of 24 dogs with subsequent local recurrence and 12 dogs with metastasis, as compared to dogs matched by breed, age, and sex with subcutaneous MCT that did not experience these events. Mitotic index, Ki67, the combination of Ki67 and AgNOR, and KIT cellular localization pattern were significantly associated with local recurrence and metastasis, thereby demonstrating their prognostic value for subcutaneous MCT. No internal tandem duplication mutations were detected in exon 11 of c-KIT in any tumors. Because c-KIT mutations have been demonstrated in only 20 to 30% of cutaneous MCT and primarily in tumors of higher grade, the number of subcutaneous MCT analyzed in this study may be insufficient to draw conclusions on the role c-KIT mutations in these tumors. KeywordsAgNOR, canine, case-control study, c-KIT, Ki67, mast cell tumor, mitotic index, prognostic markers Subcutaneous mast cell tumors (MCT) are located in the subcutis, usually surrounded by fat. Until recently, 24,35 this type was not investigated separately from its cutaneous counterpart. Subcutaneous MCT are classified by many as grade II MCT, based on current grading schemes.10,27 Because intermediate (grade II) tumors have a highly variable prognosis 10,25,26 and low interobserver agreement among pathologists, 25,26 accurate prognostic data for the subcutaneous variant of MCT are needed. In a recent retrospective survival analysis of subcutaneous MCT from 306 dogs, 35 we demonstrated that the majority of subcutaneous MCT do not behave aggressively, thus confirming the conclusion of a prior smaller study of subcutaneous MCT.24 Furthermore, our results showed that a strong predictor of survival time, time to local recurrence, and metastasis was mitotic index (MI), assessed as the number of mitotic figures per 10 high-power fields. 35MI is a valuable prognostic test 7,31 and an integral part of grading schemes for cutaneous MCT. 3,10,27 Despite this, there are drawbacks to using MI as a sole determinant for assessment of cellular proliferation. Accurate counting of mitotic figures may be influenced by field selection, plane of section, field diameter, intensity of cytoplasmic granularity (or presence of crush artifact), necrosis, and/or apoptotic cells. All of these variables can contribute to interobserver disagreement. In addition, MI detects only cells in the mitotic phase rather than the enti...

No abstract

Aumento da imunorreatividade da molécula de adesão intercelular-1 na esclera e coroide em modelo experimental de hipercolesterolemia

Olmesartan reduced the MCP-1 expression and the resultant macrophage accumulation in the choroid-sclera complex of hypercholesterolemic rabbits.

OBJECTIVE:To evaluate the effect of blocking the angiotensin II AT-1 receptor by the systemic administration of candesartan on the expression of intercellular adhesion molecule-1 in the sclera and choroid of hypercholesterolemic rabbits.METHODS:New Zealand rabbits were divided into 3 groups, as follows: GI, which was fed a rabbit standard diet; GII, which was fed a hypercholesterolemic diet; and GIII, which received hypercholesterolemic diet plus candesartan. Samples of the rabbits' sclera and choroid were then studied by hematoxylin-eosin staining and histomorphometric and immunohistochemical analyses for intercellular adhesion molecule-1 expression.RESULTS:Histological analysis of hematoxylin- and eosin-stained sclera and choroid revealed that macrophages were rarely present in GI, and GII had significantly increased macrophage numbers compared to GIII. Moreover, in GII, the sclera and choroid morphometry showed a significant increase in thickness in comparison to GI and GIII. GIII presented a significant increase in thickness in relation to GI. Sclera and choroid immunohistochemical analysis for intercellular adhesion molecule-1 expression revealed a significant increase in immunoreactivity in GII in relation to GI and GIII. GIII showed a significant increase in immunoreactivity in relation to GI.CONCLUSION:Candesartan reduced the expression of intercellular adhesion molecule-1 and consequently macrophage accumulation in the sclera and choroid of hypercholesterolemic rabbits.

No abstract

No abstract

No abstract