BCL2 and MYC are expressed at high levels in canine diffuse large B‐cell lymphoma but are not predictive for outcome in dogs treated with CHOP chemotherapy

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common haematopoietic malignancy in dogs. Recently, MYC and BCL2 expression levels determined with immunohistochemistry (IHC) were found to be prognostic in people with DLBCL. We hypothesized that canine DLBCL can be similarly subdivided into prognostic subtypes based on expression of MYC and BCL2. Cases of canine DLBCL treated with CHOP chemotherapy were retrospectively collected and 43 dogs had available histologic tissue and complete clinical follow-up. Median values of percent immunoreactive versus immunonegative cells were used to determine positive or negative expression status. Completion of CHOP was significantly associated with a positive outcome. Compared with human patients, our canine DLBCL patients had high IHC expression of both MYC and BCL2, and relative expression levels of one or both markers were not associated with clinical outcome.

RNA disruption indicates CHOP therapy efficacy in canine lymphoma

“…Knowledge gained from canine comparative oncology studies including those in canine lymphoma can augment knowledge of human disease; naturally occurring canine tumours have been explored as a better model to assess therapeutic response than xenograft mouse models [32]. Many similarities between human non-Hodgkin’s lymphoma and canine lymphoma have been identified [33, 34]; however, species differences have also been noted in tumour responses [35] and some methods which are prognostic in human disease have been shown not to be effective in dogs [9]. A number of recent studies have been carried out using canine lymphoma as a model system to evaluate novel therapies in Phase I trials [36] and examine chemoresistance [27].…”

“…A number of studies have explored methods to predict outcome in canine lymphoma including refining diagnostic staging methods using cytology and sonography to evaluate the liver and spleen [7], measurement of chemotherapy-induced neutropenia [8], assessment of the relative expression levels of BCL2 and MYC [9], the use of the modified Glasgow Prognostic Score [10]), the immunosignature at diagnosis [11], the assessment of Ki67 and its correlation with mitotic index [12] and flow cytometric characterization of S-phase fraction and ploidy in lymph node aspirates [13]. To date, no useful prognostic indicators have been established that consistently correlate with either the length or lack of remission.…”

Prognostic significance of Ki67 and its correlation with mitotic index in dogs with diffuse large B-cell lymphoma treated with 19-week CHOP-based protocol

“…7 Several prognostic factors have been identified in canine lymphoma 6,7,9 ; however, only 2 studies have specifically analyzed prognostic factors in DLBCL, to our knowledge. 2,8 Cell proliferation has been studied in different tumors, and several markers have been described in veterinary medicine. 6 Ki67 is a protein expressed at every phase of the cell cycle, except at G0, with greater expression during mitosis (M).…”

“…Ki67 and MI have been considered prognostic factors in dogs with mast cell tumor and melanoma. 13,14,17 In the 2 most recent reports discussing prognosis of dogs with DLBCL, 2,8 no relationship was found between Bcl2 and MYC immunoexpression and prognosis, 2 whereas the other study reported that a lymphocyte-to-monocyte ratio <1.2 (flow cytometry) is a prognostic factor in dogs with highgrade B-cell lymphomas. 8 Similarly, other authors quantified Ki67 by flow cytometry and established it to be a prognostic factor in dogs with B-cell lymphomas.…”

Establishment of a bioluminescent canine B-cell lymphoma xenograft model for monitoring tumor progression and treatment response in preclinical studies

“…A multitude of new drugs are entering clinical development for NHL treatment; nevertheless the approval of new therapies remains low due in part to the scarcity of clinically relevant models for validation [5]. Canine DLBCL, one of the most common neoplasia s in dogs, shares genetic, biological, molecular and clinical similarities with its human counterpart, making the dog an excellent animal model to explore novel therapeutic molecules and approaches for human DLBCL [6–10]. Moreover, dogs diagnosed with lymphoma are frequently treated with anthracycline based chemotherapy regimens, similarly to human DLBCL patients, providing realistic opportunities to explore therapeutic protocols that may translate to human clinical trials [8].…”