Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1

Ryan, Bríd M.; Konecny, G.; Kahlert, Steffen; Wang, H.-J.; Untch, Michael; Meng, Gloria; Pegram, Mark D.; Podratz, Karl C.; Crown, John; Slamon, Dennis J.; Duffy, M. J.

doi:10.1093/annonc/mdj121

Cited by 135 publications

(115 citation statements)

References 40 publications

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“…Span et al (2004) found similar relationships between survivin, grade III and lack of ER. A recent report in which enzyme-linked immunosorbent assay was used to measure survivin found high levels to relate to poorer outcome, which was independent of other factors (Ryan et al, 2006). However, two immunohistochemical studies report different findings to the present one.…”

Section: Discussioncontrasting

confidence: 62%

Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients

2007

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Established clinico -pathological factors can place patients with breast cancer into good and poor prognostic categories, but even within these groups behaviour and response to treatment can differ. This study examined the value of cell cycle and apoptotic regulatory proteins in predicting behaviour in a poor prognostic group. A total of 165 patients, all of whom had died of breast cancer with duration of survival 12 -127 months, median 38 months, were examined using immunohistochemistry for proliferation, apoptosis, p53, phosphorylated p53, p21, checkpoint kinase 2 (Chk2), bcl-2, bax, survivin and XIAP. All had received chemotherapy and/or hormonal therapy and were predominantly T2, node positive, grade III with only half oestrogen-receptor (ER) positive. High proliferation, phosphorylated p53, Chk2 and survivin expression correlated with grade III and lack of ER, whereas low proliferation, p21 and bcl-2 related to better grade and presence of ER. On univariate analysis grade, proliferation, phosphorylated p53, bcl-2, ER and survivin related to duration of survival. In multivariate analysis, grade (P ¼ 0.001) and survivin (P ¼ 0.005) were independent prognostic factors, grade III and presence of survivin relating to shorter survival. The latter was particularly for those patients receiving neoadjuvant therapy and adjuvant chemo-and hormonal therapy. The presence of the inhibitor of apoptosis protein survivin is a highly significant independent predictor of shorter duration of survival of patients with poor prognostic features, and merits investigation as a marker in other prognostic groups.

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Section: Discussioncontrasting

confidence: 62%

Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients

2007

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“…Recently many had showed survivin could be a biomarker of tumor (Waligórska-Stachura et al, 2012;Fraunholz et al, 2012). Ryan et al have found that increased survivin in breast cancer tissue indicating worse treatment response and prognosis (Ryan et al, 2006). Another report showed the elevated survivin in the bronchial aspirates could be the marker of lung cancer (Li et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Expression of Survivin and Caspase 3 in Oral Squamous Cell Carcinoma and Peritumoral Tissue

Li¹,

Chai²,

Cai³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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This study was conducted to investigate the expression of survivin and caspase 3 in oral squamous cell carcinoma and peritumoral tissue, and possible pathogenesis mechanisms. We used ELISA and western blotting to detect the protein expression levels of survivin and caspase 3 in tissue. In situ hybridization and real-time PCR were applied to assess mRNA expression levels. In this study, 13 tumor samples and 13 peritumoral tissue samples were collected from oral squamous cell carcinoma patients and 10 normal tissue samples obtained from patients without tumor. The result showed that the protein and mRNA expression of survivin in carcinoma was the highest among three types of tissue; following was that in peritumoral tissue. No difference in caspase 3 zymogen between peritumoral tissue and normal tissue could be found, while it was evidently decreased in carcinoma tissue. Activated caspase 3 was detected in normal tissue but could not be identified in peritumoral or carcinoma tissue. Our results indicate that the expression of survivin is apparently elevated in tumoral and peritumoral tissue. Expression of activated caspase 3 was not detected in tumoral tissue and the expression of caspase 3 zymogen was decreased in tumoral tissue. Our findings suggest that survivin may inhibit both synthesis and activation of caspase 3, hence inhibiting cell apoptosis and facililitating eventual development of oral squamous cell carcinoma.

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“…The increase in XIAP protein levels that we see after treatment of cells with trastuzumab may be in part due to a cellular stress response increasing translation of XIAP from the internal ribosomal entry sequence, although this needs to be tested in our experimental model. Similar to XIAP, the role of another key IAP/BIRC member, survivin, has been identified as a potential prognostic marker in breast cancer (48). An inverse correlation of survivin expression and sensitivity to lapatinib and trastuzumab has been observed in non-IBC ErbB2-overexpressing BT474 and SKBR3 cells, respectively (25,29).…”

Section: Discussionmentioning

confidence: 99%

Trastuzumab signaling in ErbB2-overexpressing inflammatory breast cancer correlates with X-linked inhibitor of apoptosis protein expression

Aird

Ding

Baras

et al. 2008

Molecular Cancer Therapeutics

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Inflammatory breast cancer (IBC) patients show poor survival and a significant incidence of epidermal growth factor receptor-2 (ErbB2) overexpression. A distinct mechanism involving increased expression of X-linked inhibitor of apoptosis protein (XIAP) and survivin, key members of the inhibitor of apoptosis protein (IAP) family, was observed post-trastuzumab (an ErbB2 monoclonal antibody) treatment in an ErbB2-overexpressing, estrogen receptor negative, IBC cellular model, SUM190PT, isolated from a primary IBC tumor. In contrast, a decrease in the IAP expression was observed in the non-IBC, ErbB2-overexpressing SKBR3 cells in which trastuzumab treatment also decreased p-AKT and cell viability. Further, in SUM190PT cells, therapeutic sensitivity to GW583340 (a dual epidermal growth factor receptor/ErbB2 kinase inhibitor) corresponded with XIAP down-regulation and abrogation of XIAP inhibition on active caspase-9 release. Specific small interfering RNA -mediated XIAP inhibition in combination with trastuzumab caused decrease in inactive procaspase-9 and inhibition of p-AKT corresponding with 45% to 50% decrease in cell viability in the SUM190PT cells, which have high steady-state p-AKT levels. Further, embelin, a small-molecule inhibitor that abrogates binding of XIAP to procaspase-9, caused significant decrease in SUM190PT viability. However, embelin in combination with trastuzumab failed to affect SUM190PT viability because it has no direct effect on XIAP, which is induced by trastuzumab treatment. These data have identified a novel functional link between ErbB2 signaling and antiapoptotic pathway mediated by XIAP. Blockade of the IAP antiapoptotic pathway alone or in combination would be an attractive strategy in IBC therapy.

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Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1

Abstract: The independent prognostic relevance of survivin, when combined with previous data from model systems implicating survivin in the inhibition of apoptosis, suggests that survivin may be a suitable target for future therapeutic strategies.

Cited by 135 publications

References 40 publications

Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients

Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients

Expression of Survivin and Caspase 3 in Oral Squamous Cell Carcinoma and Peritumoral Tissue

Trastuzumab signaling in ErbB2-overexpressing inflammatory breast cancer correlates with X-linked inhibitor of apoptosis protein expression

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