Prognostic Significance of Survivin and Caspase-3 Immunohistochemical Expression in Patients with Diffuse Large B-cell Lymphoma Treated with Rituximab and CHOP

Mitrović, Zdravko; Ilić, Ivana; Aurer, Igor; Kinda, Sandra Bašić; Radman, Ivo; Dotlić, Snježana; Ajduković, Radmila; Labar, Boris

doi:10.1007/s12253-010-9304-4

Cited by 13 publications

(16 citation statements)

References 21 publications

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“…Although both groups found three staining patterns in diffuse large B-cell lymphoma, including cytoplasmic, nuclear, and mixed staining, neither group found a significant difference between any type of survivin expression and patient survival. 36,37 Variations reported from different studies may have resulted from low sensitive immunohistochemical method, low concentration of survivin in the cytoplasm, and different surviving antibodies used in the study. In this study, we only observed predominant nuclear staining pattern of survivin that correlated with poorer survival in activated B cell-like diffuse large B-cell lymphoma and in patients with wild-type p53 overexpression.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy

et al. 2015

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Survivin, a member of the inhibitor of apoptosis protein family, is overexpressed in a variety of human neoplasms. The prognostic significance of survivin expression in diffuse large B-cell lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is unclear. We used standard immunohistochemistry methods to quantify survivin expression in 463 patients with de novo diffuse large B-cell lymphoma who received the R-CHOP. Of the 463 patients, 269 (58%) had survivin overexpression with a cutoff of 425%, associated with an International Prognostic Index score of 42 (P = 0.015), disease in ≥ 2 extranodal sites (P = 0.011), and a high Ki-67 index (Po 0.0001). Among patients with activated B cell-like disease, the overall survival rate of survivin-positive patients was significantly lower than that of survivinnegative patients (P = 0.033); multivariate analysis confirmed that in these patients, survivin overexpression was an independent prognostic factor for survival. Among patients with wild-type p53 overexpression, the overall survival and progression-free survival rates of the survivin-positive group were significantly lower than those of the survivin-negative group (P = 0.035 and P = 0.04 respectively). In STAT3-positive patients, survivin overexpression was associated with significantly better survival. Among patients with activated B cell-like disease, survivin-positive compared with survivin-negative groups had significantly different gene expression signatures, including genes involved in mitosis or tumor cell proliferation. Our results indicate that survivin is an

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Section: Discussionmentioning

confidence: 99%

“…35 However, in the R-CHOP era, studies on the prognostic significance of survivin in diffuse large B-cell lymphoma reported in the literature are conflicting. 36,37 In this study, we investigated survivin expression and its prognostic impact in 463 patients with de novo diffuse large B-cell lymphoma who were treated with the standard R-CHOP regimen.…”

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confidence: 99%

Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy

et al. 2015

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“…In human NHLs variable staining pattern of survivin is also observed. In some studies conducted for example on diffuse large B cell lymphomas (DLBCL) the nuclear staining pattern predominated (Martinez et al 2004, Vassallo et al 2010 while in other cytoplasmic reaction (Ambrosini et al 1997, Adida et al 2000 or both patterns (Mitrović et al 2011) have been observed. Similarly, in anaplastic large cell lymphoma different patterns of staining reaction have been found (Vassallo et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…It also seems to have a roles in tumorigenesis, drug resistance and metastases (Dohi et al 2004, Li andLing 2006). Moreover, in many tumors including hematological neoplasms it has been shown as prognostic marker of aggressive and unfavorable form of disease (Adida et al 2000, Altieri 2003, Martinez et al 2004, Urbaniak 2004, Mitrović et al 2011. Survivin is also considered as target for cancer therapy (Altieri 2003, Urbaniak 2004, Li and Ling 2006.…”

Section: Introductionmentioning

confidence: 99%

Survivin expression in canine lymphomas in relation with proliferative markers

Sokołowska¹,

Urbańska²,

Gizinski³

et al. 2015

Polish Journal of Veterinary Sciences

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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.

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“…This means that, although survivin was a negative prognostic factor in the analysis of the abovementioned studies, children with high survivin did not necessarily have a poor outcome, which is in line with our findings. In fact, there are recent reports that show that despite the initial findings pointing survivin as a prognostic factor for several types of cancer, there are also many other types for which survivin is not [39][40][41][42][43].…”

Section: Discussionmentioning

confidence: 99%

Lack of Prognostic Significance of Survivin in Pediatric Medulloblastoma

Faccion

Ferreira

Fonseca

et al. 2011

Pathol. Oncol. Res.

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Medulloblastoma (MDB) is the most common malignant cerebellar tumor in children. Because of the significant rate of mortality and treatment-related morbidity, the identification of prognostic factors could lead to a more accurate selection of patients who can benefit from a less aggressive therapy and improve risk stratification. Survivin is an inhibitor of apoptosis protein (IAP), the expression of which has been associated with worse prognosis in MDB. However, both of its subcellular localizations may contribute to tumor progression, and ultimately, survivin subcellular localization prognostic value depends on tumor type biological features. The goal of this study was to analyze these survivin features in the pediatric MDB tumor samples and its impact on clinical outcome. Survivin expression and subcellular localization were accessed by immunohistochemistry in a series of 41 tumor samples. Kaplan-Meier survival curves were compared using the log-rank test. Survivin expression ranged from completely absent to fully present in a notably higher pattern of nuclear localization than cytoplasmic (19 of 41 versus 4 of 41, respectively). However, survivin expression and subcellular localization were not associated with five-year overall survival or metastasis status at diagnosis, which was the only statistically significant prognostic factor in our series (p = 0.008). Taken together, our results suggest that survivin expression should be further studied in large, multicenter series to determine its accurate impact on prognosis and pathobiology of pediatric MDB.

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Prognostic Significance of Survivin and Caspase-3 Immunohistochemical Expression in Patients with Diffuse Large B-cell Lymphoma Treated with Rituximab and CHOP

Cited by 13 publications

References 21 publications

Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy

Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy

Survivin expression in canine lymphomas in relation with proliferative markers

Lack of Prognostic Significance of Survivin in Pediatric Medulloblastoma

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