Survivin expression in canine lymphomas in relation with proliferative markers.

Survivin is a member of apoptosis inhibiting proteins family. Apart from its antiapoptotic activity it plays a critical role in regulating the cell cycle and mitosis. It is overexpressed in most human malignancies. While the prognostic significance of survivin expression is widely investigated in human non-Hodgkin's lymphomas, little is known about its expression in canine lymphomas. The aim of the study was to evaluate the expression of survivin in canine lymphomas in relation to proliferation markers (mitotic index and percentage of Ki67-positive cells). Survivin was found in all examined lymphomas belonging to 6 different morphological subtypes with nuclear immunoreactivity. In most of lymphomas (18/25) survivin expression ranged 10%-25% of positive cells. Only single cases had lower (0-10% positive cells, 1/25) or higher (25-50% and > 50% positive cells, 5/25 and 1/25, respectively) index of survivin. Neither mitotic index nor proliferative index correlated with survivin expression when the values quantified randomly in whole specimens were compared. However, when survivin expression were quantified in selected tumor areas of low and high proliferation activity the high correlations between survivin expression and proliferation index were found. The results indicated that survivin is commonly expressed in canine lymphomas. Nuclear labelling together with the relation of its expression and proliferative activity in highly proliferative areas of neoplastic tissue suggest a potential role of survivin in cell cycle activation in canine lymphoma cells. However, further studies of the relation between expression of survivin and other proteins involved in cell cycle regulation are needed. Moreover, the results suggest that survivin may pose the therapeutic target in canine lymphomas.

Immunohistochemical detection of P-glycoprotein in various subtypes of canine lymphomas.

Combination chemiotherapy is the current standard of care for dogs with lymphoma. Multidrug resistance is one of the most important factors contributing to the efficacy of chemiotherapy. The major protein responsible for this phenomenon is P-glycoprotein. Little is known about P-glycoprotein expression in particular subtypes of lymphomas. The aim of the study was evaluation of P-glycoprotein expression in various subtypes of canine lymphomas. Positive reaction with P-glycoprotein was found in 12/25 cases of various morphological subtypes of lymphomas, however, in 3/11 lymphomas the percentage of positively weakly stained cells was < 10% and those tumors were also considered negative. Tumors with 10-50% P-glycoprotein positive cells were found in single cases of centroblastic and centroblastic-centrocytic tumors. In 5 lymphomas P-glycoprotein expression exceeded 50% of tumor cells. Those cases were found among centroblastic, centroblastic-centrocytic, lymphoblastic and Burkitt-like subtypes. Positive reaction was observed mainly in the cell cytoplasm, however, in some cases prominent perinuclear dot-like staining pattern was found. In 2 cases focal staining pattern comprised dominant type of immunolabelling. Among all lymphomas containing P-glycoprotein positive cells intensity of imunolabelling was assessed as weak (6/25), moderate (2/25) and strong (3/25). Our results indicate that P-glycoprotein expression is present in nearly one third of newly diagnosed canine lymphomas of different morphological subtypes including those most commonly occurring, such as cenroblastic lymphomas. Hence, determination of P-glycoprotein expression at the time of diagnosis could provide valuable information for the design of treatment protocols. Moreover, our results have shown that P-glycoprotein expression in canine tumors could be located in Golgi-zone.