Prognostic Factors for Treated Canine Malignant Lymphoma

Abstract

Abstract. The aim of this study was to investigate the prognostic importance of different clinical, immunohistologic and tumorproliferation characteristics in dogs with malignant lymphoma treated with chemotherapy. From 74 dogs with malignant lymphoma at least one enlarged peripheral lymph node was taken for biopsy before chemotherapy following a standardized protocol (vincristine, cyclophosphamide, prednisolone, doxorubicin, and L-asparaginase). The variables evaluated as prognostic factors were age, sex, and tumor stage, as well as histomorphologic grade (Kiel classification, Working Formulation), immunophenotype (using markers for CD3 and CD79a), and cell proliferation (Ki-67, proliferation cell nuclear antigen, mitotic index, and argyrophil nucleolar organizer regions [AgNORs]) in extirpated lymph nodes. All markers were used on routinely formalin-fixed, paraffin-embedded tissues. The AgNORs were assessed qualitatively, based on the AgNOR pattern distribution, and quantitatively using image analysis and routine counting. In both univariate and multivariate survival analyses, AgNORs were a valuable prognostic marker for the treatment of canine malignant lymphomas. Based on the results of the multivariate analysis longer survival time correlated with a B-cell type, a larger mean AgNOR area, a larger total AgNOR area, a shorter distance between two AgNORs, and a smaller AgNOR area to nucleus ratio. Longer disease-free survival time correlated with a smaller number of AgNORs per nucleus, a larger mean AgNOR area, a larger maximal AgNOR area, and a larger total AgNOR area. This study clearly demonstrates the additional benefit of the use of AgNORs in predicting treatment outcome in dogs with malignant lymphoma.

Argyrophilic Nucleolar Organizing Regions and Ki67 Equally Reflect Proliferation in Fine Needle Aspirates of Normal, Hyperplastic, Inflamed, and Neoplastic Canine Lymph Nodes (n = 101)

“…Although digital image analysis was used in the study from Kiupel et al, 1 the AgNOR count was performed manually by Vail et al 4 and Vajdovich et al 5 A previous investigation, however, failed to demonstrate a correlation between visual and computer-assisted AgNOR quantification in tissue sections of 20 patients with non-Hodgkin's lymphoma. 25 The number of cells evaluated in our study was with a median number of 113, comparable with that assessed by Kiupel et al 1 React.h., reactive hyperplasia; L.ad., lymphadenitis; lympho., lymphoma.…”

“…However, the assessment of AgNORs in lymph-node biopsy specimens of dogs with lymphoma is superior to the Ki67 count regarding its significance as a prognostic marker for predicting treatment response. 1 Only a few studies exist that evaluated the influence of the immunophenotype of the lymphoma on proliferation markers in dogs. 38 In the dogs evaluated here, higher AgNOR count/cell, AgNOR area/cell, and percentage of Ki67 positive cells were evident in B-cell lymphoma compared with dogs with T-cell lymphoma, indicating both a higher percentage of proliferating cells and a higher speed of cellular proliferation in B-cell lymphomas.…”

“…[1][2][3] However, there are only few studies that report the use of AgNOR staining in fine needle aspirates (FNA) of canine lymph nodes. The concurrent investigation of lymph-node biopsy specimens and FNAs taken from 51 dogs with lymphoma revealed a good correlation between the results obtained from biopsy specimens and those obtained from a cytologic specimen (r 5 0.98).…”

Chromosome aberrations in canine multicentric lymphomas detected with comparative genomic hybridisation and a panel of single locus probes

“…Greenlee et al, 1990;Kuipel et al, 1999;Dobson et al, 2001), but it is evident that additional such aids are required in order to generate more refined modes of subclassification. Coupled with their physiological comparability, extensive genome homology, shared environment and the similarity in their clinical presentation of the disease, the domestic dog (Canis familiaris, CFA) represents an ideal system in which to study human multicentric lymphoma.…”

Association of nucleolar organizing regions and Ki-67 expression with recurrence rate of hair follicle tumor in dogs

“…Several neoplastic characteristics associated with recurrence and survival rate of patients have been studied in order to verify their relationship with prognosis in the cases of canine transmissible venereal tumor, canine mammary tumor, canine malign melanoma, canine lymphosarcoma, and canine mastocytomas. These characteristics are: clinical staging system (Bozlu et al, 2002), histological evaluation of clean surgical margins, number of mitoses/field (Greattu et al, 2004), nuclear diameter (Lohr et al, 1997), quantification of nucleolar organizing regions (NORs) (Orell et al, 1991;Bostock et al, 1992;Kiupel et al, 1999;Ceccarelli et al, 2000;Silva et al, 2006), and the immunohistochemical expression of cell proliferation, (Scase et al, 2006;Seguin et al, 2006) among others. The histochemical method to identify and quantify NORs has been used in several types of neoplasms, isolated or in association with Ki-67 expression (Lohr et al, 1997).…”