High Survivin Expression Research Articles

Nuclear survivin expression is associated with a poor prognosis in Caucasian non-small cell lung cancer patients

BackgroundThe role of the nuclear protein survivin in non-small cell lung cancer (NSCLC) remains controversial. To clarify the association of survivin with survival in NSCLC, we performed a meta-analysis of the literature with meta-analysis. MethodsTrials were selected for further analysis if they provided an independent assessment of nuclear survivin in NSCLC and reported the survival data in the context of survivin status. A total of 7 trials, which comprised 823 patients, were included in the meta-analysis. Sensitivity analyses were conducted using the patient's disease stage, IHC cutoff value, and ethnicity. ResultsThe combined hazard ratio (HR) of 1.54 [95% CI, 0.79–3.02; test for heterogeneity p<0.001] suggests that high nuclear survivin expression has no impact on patient survival. However, when the studies were restricted to Caucasian patients, high levels of nuclear survivin expression were correlated with reduced survival (HR 2.38, 95% CI=1.60–3.52; p=0.189 for heterogeneity). In addition, the heterogeneity disappeared when the analysis was restricted to Caucasians. ConclusionNuclear survivin expression is associated with poor prognosis for Caucasian NSCLC patients.

High survivin expression in premalignant and malignant kidney lesions

Results Survivin protein was expressed in 29 of the 40 (72.5%) cases of RCC compared with its expression in nine of 14 (64.3%) cases of RIN; this difference was statistically insignificant. The positive rate of survivin was strongly associated with pathological grades, clinical stages, and lymph metastasis in RCC (P < 0.05). In contrast, normal and pyelonephritic renal tissues did not express survivin.

High survivin expression as a risk factor in patients with anal carcinoma treated with concurrent chemoradiotherapy

PurposeTo investigate the prognostic value of survivin expression in pretreatment specimens from patients with anal cancer treated with concurrent 5-FU and mitomycin C-based chemoradiation (CRT).Material and methodsImmunohistochemical staining for survivin was performed in pretreatment biopsies of 62 patients with anal carcinoma. Survivin expression was correlated with clinical and histopathological characteristics as well as local failure free- (LFFS), distant metastases free- (DMFS), cancer specific- (CSS), and overall survival (OS).ResultsSurvivin staining intensity was weak in 10%, intermediate in 48% and intense in 42% of the patients. No association between survivin expression and clinicopathologic factors (tumor stage, age and HIV status) could be shown. In univariate analysis, the level of survivin staining was significantly correlated with DMFS (low survivin vs. high survivin: 94% vs. 74%, p = 0.04). T-stage, N-stage and the tumor grading were significantly associated with OS and CSS and with DMFS and LFFS, respectively. In multivariate analysis, survivin was confirmed as independent prognostic parameter for DMFS (RR, 0.04; p = 0.02) and for OS (RR, 0.27; p = 0.04).ConclusionOur results demonstrated that the level of pretreatment survivin is correlated with the clinical outcome in patients with anal carcinoma treated with concurrent CRT. Further studies are warranted to elucidate the complex role of survivin for the oncologic treatment and to exploit the protein as a therapeutic target in combined modality treatment of anal cancer.

Abstract 4500: Clinical significance of survivin expression in urothelial carcinoma of the bladder

Abstract Objective: Survivin is one of the inhibitors of apoptosis protein family and plays an important role in carcinogenesis. Survivin also has been reported to be related with poor clinical outcome in various malignancies. The aim of this study is to examine the association between survivin expression and clinical outcome in urothelial carcinoma of the bladder. Materials and methods: A total of 56 histopathologically confirmed urothelial carcinoma of bladder (UCB) patients were recruited from the Department of Urology of Chiayi Christian Hospital and Chi-Mei Medical Center from August 2006 to May 2007. Immunohistochemistry (IHC) analysis was performed to determine the expression level of survivin in tumor and adjacent normal tissues. One normal human urothelial cell: HUC4449 and nine urothelial carcinoma cell lines which are TSGH8301, 5637, BFTC905, BFTC909, HT1376, TCC SUP, J82, T24 and HT1197 for survivin mRNA analysis by quantitative real-time PCR. The –31 C/G polymorphism in survivin gene was determined using PCR-RFLP method. The effects of a higher expression level of survivin on disease-free survival (DFS) and overall survival (OS) were estimated using Cox proportional hazard models. Results: The frequency of low, moderate and higher expression of survivin in tumor tissues of UCB were 16.1%, 39.3% and 44.6%, respectively. The frequency of high expression of survivin was significantly higher in muscle-invasive tumors (66.6%) than in non-muscle invasive tumors (34.2%) (P=0.042). The frequency of high expression of survivin was significantly higher in poor-differentiated (85.7%) than in moderate- differentiated tumors (30.8%) (P= 0.0014). The survivin mRNA expression (Log2 fold change were 3.41∼5.30) in various grade (G2-G4) urothelium carcinoma cell lines were all higher than normal human urothelial cell. Moreover, the higher frequency of risk genotypes (C/C+C/G) was observed in median and high survivn expression groups. In a multivariate analysis, high survivin expression was predictive of inferior OS (HR= 12.3, P=0.02). Conclusion: These findings suggest that the high expression of survivin is not only associated with tumor stage and grade of tumors but also may be predictive of inferior overall survival of urothelail carcinoma of the bladder. Keywords: survivin; bladder; urothelial carcinoma; immunohistochemistry, disease-free survival; overall survival Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4500. doi:1538-7445.AM2012-4500

Abstract 714: Survivin expression in patients with resected pancreatic adenocarcinoma

Abstract Introduction: Pancreatic cancer remains highly refractory to treatment and biomarkers of treatment responsiveness are urgently needed. Survivin is an inhibitor of apoptosis and one such potential marker. Undetectable in most normal differentiated and non-proliferating tissues, it is highly expressed in cancer. We measured pancreatic cancer survivin expression and examined its association with differential treatment response. Methods: We constructed 4 pancreatic cancer tissue microarrays with 1mm duplicate cores using tumor samples from 88 resected pancreatic cancer patients at our center. They were then followed with 60 patients receiving chemotherapy or radiation, both as adjuvant therapy and also for palliative treatment upon recurrence. We measured survivin expression using highly quantitative automated immunofluorescence via AQUA R(HistoRx, Branford CT). Scores were individually reported for the nuclear, cytoplasmic and total cellular compartments, and validated by the pathologist. Results: Median survivin AQUA scores were: nuclear 5838 (range 2126-13728), cytoplasm 4177 (2173-9914) and total 4543 (2120-10344). Survivin expression was significantly higher in nodal specimens compared to primary tumor in nucleus (p=0.02), cytoplasm (p=0.006) and in total (p=0.0095). Higher cytoplasmic survivin correlated with higher grade (p=0.03), and primary tumor location in head compared to body or tail (p=0.03). There was a trend toward higher nuclear survivin in younger (p=0.08) and female patients (p=0.08). Disease-free survival (DFS) was significantly longer in patients with high compared to low nuclear survivin (p=0.048), using median as the cut-off. This effect was greater for patients treated with gemcitabine (p=0.0481) than those treated with 5-FU (p=0.0698) or radiation therapy (p=0.094). Overall survival for all patients was not different in the higher than median group compared to lower group patients (p=0.300). There was a trend toward longer overall survival (OS) for patients whose tumors had high nuclear survivin in those treated with fluorouracil (p=0.0856), gemcitabine (p=0.0868) or radiation therapy (p=0.0862). Discussion: Survivin expression is higher in nodal metastases than primary resected pancreatic cancer tumors and is associated with particular clinical and pathologic characteristics. High nuclear survivin expression is associated with longer DFS in patients with resected pancreatic cancer. This effect is most pronounced in patients treated with gemcitabine. Further examination of survivin in a larger series of pancreatic cancers is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 714. doi:1538-7445.AM2012-714

Survivin expression in human lung cancer and the influence of its downregulation on the biological behavior of human lung cancer cells

The aim of the present study was to detect the expression of survivin in human lung cancer and to investigate the influence of its downregulation on the biological behavior of A549 lung cancer cells. The high expression of survivin in human lung cancer was verified by immunohistochemistry. Survivin small interfering RNA (siRNA) and unrelated sequence were synthesized and the siRNA lentiviral vector was constructed. The vector was transfected into A549 lung cancer cells, in which the clone with stable expression was screened out. We blocked the expression of survivin mRNA and protein by RNA interference (RNAi) technique. The downregulation of survivin mRNA and protein expression was confirmed by real-time quantitative PCR and western blotting. The proliferative activity and growth rate of A549 cells were determined by colony formation assay and mononuclear cell direct cytotoxicity assay (MTT assay). The reconstituted basement membrane (RBM) penetrating capacity was determined by cell invasion assay. The cell movement and migratory capacity were detected by wound-healing repair assay. The results showed that the sequence-specific siRNA significantly downregulated the expression of survivin at both the mRNA and protein levels. Downregulation of survivin expression dramatically decreased the invasive and metastatic capacities of the cells, suppressed the proliferation, decelerated the rate of growth, reduced the number of clones on soft agar and decreased the capacity of RBM penetration and migration. In conclusion, survivin, which plays an important role in carcinogenesis and development of lung cancer, can be effectively downregulated using the RNAi technique.

High expression of nuclear survivin and Aurora B predicts poor overall survival in patients with head and neck squamous cell cancer

Survivin is one of the apoptosis inhibitor proteins. Together with AuroraB, it also plays a role in regulating several aspects of mitosis. High expression of these markers is correlated with malignant behavior of various cancers and resistance to therapy. Our aim was to evaluate the prognostic role of these markers in head and neck cancers. We evaluated the expression of Aurora B and survivin in tissue specimens of 58 patients with head and neck squamous cell carcinoma using immunohistochemistry. Patients who showed high expression of cytoplasmic and nuclear survivin and Aurora B had significantly shorter overall survival (p = 0.036, p < 0.000, p = 0.032, respectively). In multivariate analysis, high expression of nuclear survivin was the only independent negative prognostic factor (p = 0.024). Moreover, it was found that high co-expression of nuclear survivin and Aurora B had a negative effect on survival in univariate (p < 0.000) and multivariate (p < 0.000) analyses. The negative prognostic values of high expression of Aurora B and high co-expression of nuclear survivin and Aurora B on survival were shown. These findings suggest that co-expression of nuclear survivin and Aurora B can be useful diagnostic markers and therapeutic targets for head and neck squamous cell carcinoma. However, further studies with a larger number of patients in a more homogeneous disease group are needed to confirm the conclusion.

Prognostic Relevance of Survivin in Pancreatic Endocrine Tumors

BackgroundBetter prognostic markers are needed for pancreatic endocrine tumors. Survivin is an apoptosis inhibitor that is suggested to have a negative prognostic impact in several tumor types. Contradictory data exist, especially regarding the significance of a nuclear versus cytoplasmic location of survivin. The prognostic relevance of nuclear and cytoplasmic survivin expression in pancreatic endocrine tumors—controlled for the tumor Ki-67 index, World Health Organization classification, and TNM stage—was investigated.MethodsA total of 111 patients treated at a tertiary referral center were retrospectively evaluated. Clinical data were gathered from medical records. Immunohistochemistry for survivin and Ki-67 was performed on paraffin-embedded tissue. Univariate and multivariate Cox analyses were performed.ResultsPatients with tumors that had <5% survivin-positive nuclei had a mean survival of 225 months [95% confidence interval (CI) 168–281]. The corresponding figure for patients with 5 to 50% survivin-positive tumor cell nuclei was 101 months [95% CI 61–140; hazard ratio (HR) 2.4; P < 0.01) and with >50% survivin-positive nuclei 47 months (95% CI 24–71; HR 4.9; P < 0.001). Nuclear survivin expression in >50% of the tumor cells was an independent marker of a poor prognosis (HR 5.7; P < 0.01). Cytoplasmic survivin was not a significant prognostic factor in the multivariate analysis (HR 0.94; P = 0.90).ConclusionsHigh expression of nuclear survivin is a significant marker of a poor prognosis in patients with a pancreatic endocrine tumor.

Nuclear survivin expression is a positive prognostic factor in taxane-platinum-treated ovarian cancer patients

BackgroundSurvivin is an inhibitor of apoptosis and a regulator of mitotic progression. TP53 protein is a negative transcriptional regulator of survivin. The aim of our study was to evaluate the clinical significance of survivin expression in advanced stages ovarian cancer with respect to the TP53 status.MethodsSurvivin and TP53 expression was evaluated immunohistochemically in 435 archival samples of ovarian carcinomas (244 patients were treated with platinum/cyclophosphamide-PC/PAC; 191-with taxane-platinum (TP) agents). Univariate and multivariate statistical analyses were performed in patients groups divided according to the administered chemotherapeutic regimen, and in subgroups with and without TP53 accumulation (TP53+ and TP53-, respectively).ResultsNuclear and cytoplasmic survivin expression was observed in 92% and 74% of the carcinomas, respectively. In patients treated with TP, high nuclear survivin expression decreased the risk of disease recurrence and death, and increased the probability of high platinum sensitivity (p < 0.01), but only in the TP53(+) group, and not in the TP53(-) group.ConclusionsIt appears that TP53 status determines the clinical importance of nuclear survivin expression in taxane-platinum treated ovarian cancer patients.

Overexpression of survivin is correlated with increased invasion and metastasis of colorectal cancer

The aim of this study was to investigate the association of survivin expression with metastasis of colorectal cancer (CRC). RT-PCR and Western blot assays were performed to detect survivin expression in CRC cells and normal intestinal epithelial cell. The expression of survivin gene was also detected in 15 CRC tissues, surrounding and adjacent colon tissues. Moreover, survivin expression in 48 CRC tissues with or without lymph node metastasis was analyzed. Multivariate analysis for lymph node metastasis was performed using logistic regression model. RNA interference was used to inhibit survivin expression in CRC cells and analyze its effect on invasion and metastasis of CRC cells. The expression levels of survivin mRNA and protein were higher in CRC cells than in normal intestinal epithelial cell line. The average levels of survivin mRNA and protein were higher in CRC tissues than surrounding or adjacent colon tissues (P < 0.05). High survivin expression was an independent factor for predicting lymph node metastasis of CRC (P = 0.043). RNAi-mediated survivin knockdown could significantly inhibit in vitro invasion and in vivo metastasis of CRC cells, which might be inactivation of matrix metalloproteinases. Targeting survivin will be a potential strategy to suppress metastasis of CRC.

Total Survivin and acetylated Survivin correlate with distinct molecular subtypes of breast cancer

Global gene expression profiling studies led to the recent classification of breast cancer into 4 distinct molecular subtypes including luminal, human epidermal growth factor receptor 2 enriched, basal like, and unclassified. Here, we used immunohistochemistry to evaluate expression of the antiapoptotic protein Survivin and its recently described acetylated form, Survivin acetyl129, in normal breast tissue and in 226 primary breast tumors of different molecular subtypes. Correlation of Survivin expression with molecular markers and its impact on patient outcomes were analyzed. Eighty-four percent of basal-like tumors expressed high levels of total Survivin, whereas 52% of luminal tumors expressed high levels of acetylated Survivin (P < .001). Overall survival (91%) for tumors expressing low levels of total Survivin was better than that for tumors expressing high levels of total Survivin (72%, P = .02), whereas the reverse was true for tumors expressing acetylated Survivin. In hierarchical cluster analysis, total Survivin clustered with basal marker expression, whereas acetylated Survivin clustered with luminal marker expression. In multivariate analysis, high total Survivin expression was an independent predictor of worse overall survival in patients with breast cancer (relative risk, 11; P < .01). These data indicate that high levels of total Survivin predict poor outcome in patients with grade 3 invasive ductal carcinoma and correlate directly with a basal-like phenotype. In contrast, high expression of the acetylated form of the protein associates with a favorable outcome and preferentially correlates with luminal-type tumors. Survivin likely has different functions in distinct breast cancer subtypes, and diagnostic strategies that incorporate immunohistochemical markers that detect both Survivin forms may help better strategize patient risk and direct therapy.

Inhibitory effect of Survivin promoter-regulated oncolytic adenovirus carrying P53 gene against gallbladder cancer

Gene therapy has become an important strategy for treatment of malignancies, but problems remains concerning the low gene transferring efficiency, poor transgene expression and limited targeting specific tumors, which have greatly hampered the clinical application of tumor gene therapy. Gallbladder cancer is characterized by rapid progress, poor prognosis, and aberrantly high expression of Survivin. In the present study, we used a human tumor-specific Survivin promoter-regulated oncolytic adenovirus vector carrying P53 gene, whose anti-cancer effect has been widely confirmed, to construct a wide spectrum, specific, safe, effective gene-viral therapy system, AdSurp-P53. Examining expression of enhanced green fluorecent protein (EGFP), E1A and the target gene P53 in the oncolytic adenovirus system validated that Survivin promoter-regulated oncolytic adenovirus had high proliferation activity and high P53 expression in Survivin-positive gallbladder cancer cells. Our in vitro cytotoxicity experiment demonstrated that AdSurp-P53 possessed a stronger cytotoxic effect against gallbladder cancer cells and hepatic cancer cells. The survival rate of EH-GB1 cells was lower than 40% after infection of AdSurp-P53 at multiplicity of infection (MOI) = 1 pfu/cell, while the rate was higher than 90% after infection of Ad-P53 at the same MOI, demonstrating that AdSurp-P53 has a potent cytotoxicity against EH-GB1 cells. The tumor growth was greatly inhibited in nude mice bearing EH-GB1 xenografts when the total dose of AdSurp-P53 was 1 × 10 9 pfu, and terminal dUTP nick end-labeling (TUNEL) revealed that the apoptotic rate of cancer cells was (33.4 ± 8.4)%. This oncolytic adenovirus system overcomes the long-standing shortcomings of gene therapy: poor transgene expression and targeting of only specific tumors, with its therapeutic effect better than the traditional Ad-P53 therapy regimen already on market; our system might be used for patients with advanced gallbladder cancer and other cancers, who are not sensitive to chemotherapy, radiotherapy, or who lost their chance for surgical treatment.

Biomarkers and microsatellite instability analysis of curettings can predict the behavior of FIGO stage I endometrial endometrioid adenocarcinoma

The prognostic value of molecular biomarkers, microsatellite instability, DNA ploidy and morphometric mean shortest nuclear axis in endometrial cancer is conflicting, possibly due to the fact that different studies have used mixtures of histotypes, FIGO stages and different non-standardized non-automated methods. We have evaluated the prognostic value of classical prognostic factors, molecular biomarkers, microsatellite instability, DNA ploidy and morphometric mean shortest nuclear axis in a population-based cohort of FIGO stage I endometrial endometrioid adenocarcinomas. Curettings of 224 FIGO stage I endometrial endometrioid adenocarcinoma patients were reviewed. Clinical information, including follow-up, was obtained from the patients' charts. Microsatellite instability and morphometric mean shortest nuclear axis were obtained in whole tissue sections and molecular biomarkers using tissue microarrays. DNA ploidy was analyzed by image cytometry. Univariate (Kaplan–Meier method) and multivariate (Cox model) survival analysis was performed. With median follow-up of 66 months (1–209), 14 (6%) patients developed metastases. Age, microsatellite instability, molecular biomarkers (p16, p21, p27, p53 and survivin) and morphometric mean shortest nuclear axis had prognostic value. With multivariate analysis, combined survivin, p21 and microsatellite instability overshadowed all other variables. Patients in which any of these features had favorable values had an excellent prognosis, in contrast to those with either high survivin or low p21 (97 vs 78% survival, P<0.0001, hazard ratio=7.8). Combined high survivin and low p21 values and microsatellite instability high identified a small subgroup with an especially poor prognosis (survival rate 57%, P=0.01, hazard ratio=5.6). We conclude that low p21 and high survivin expression are poor prognosis indicators in FIGO stage I endometrial endometrioid adenocarcinoma, especially when high microsatellite instability occurs.

Histone Deacetylase Inhibitor Belinostat Represses Survivin Expression through Reactivation of Transforming Growth Factor β (TGFβ) Receptor II Leading to Cancer Cell Death

Survivin is a cancer-associated gene that functions to promote cell survival, cell division, and angiogenesis and is a marker of poor prognosis. Histone deacetylase inhibitors induce apoptosis and re-expression of epigenetically silenced tumor suppressor genes in cancer cells. In association with increased expression of the tumor suppressor gene transforming growth factor β receptor II (TGFβRII) induced by the histone deacetylase inhibitor belinostat, we observed repressed survivin expression. We investigated the molecular mechanisms involved in survivin down-regulation by belinostat downstream of reactivation of TGFβ signaling. We identified two mechanisms. At early time points, survivin protein half-life was decreased with its proteasomal degradation. We observed that belinostat activated protein kinase A at early time points in a TGFβ signaling-dependent mechanism. After longer times (48 h), survivin mRNA was also decreased by belinostat. We made the novel observation that belinostat mediated cell death through the TGFβ/protein kinase A signaling pathway. Induction of TGFβRII with concomitant survivin repression may represent a significant mechanism in the anticancer effects of this drug. Therefore, patient populations exhibiting high survivin expression with epigenetically silenced TGFβRII might potentially benefit from the use of this histone deacetylase inhibitor.

Significant Elevation of Survivin and Livin Expression in Human Colorectal Cancer: Inverse Correlation between Expression and Overall Survival

Background: Survivin and livin are novel members of the inhibitor of apoptosis protein family, which have rarely been studied in human colorectal cancer (CRC). This study aims to examine their expression and association with clinicopathological factors and prognosis in CRC, and evaluate the possibility of their use as biomarkers for CRC. Patients and Methods: We investigated the expression of survivin and livin in 61 CRC samples using immunohistochemical staining (Envision) and correlated it with the survival of these patients using log-rank test and correlation analysis. Results: Among the 61 cases, 60.7 and 54.1% were positive for expression of survivin (p < 0.05) and livin (p < 0.05). No expression of survivin and livin was detected in normal colorectal mucosa. An inverse correlation (r = –0.9916) between the increased survivin and livin levels and overall survival was observed in univariate survival analysis. The expression of both proteins was not correlated with age, gender, degrees of differentiation, and TNM stage (p < 0.05) in malignancies. Conclusions: High expression of both survivin and livin may influence the prognosis of CRC. This finding opens new perspectives for CRC prognosis because survivin and livin can both be used as biomarkers or potential therapeutic targets.

High expression of survivin predicts poor prognosis in esophageal squamous cell carcinoma following radiotherapy

Radiotherapy is one of the main treatments for esophageal squamous cell carcinoma, but there are still no biomarkers to differentiate patients who will benefit from radiation. Although treatment with a combination of radiotherapy with chemotherapy, and/or surgery improves the prognosis of patients, no biomarkers can distinguish between the responses obtained with the combined therapies. Therefore, in this study, we selected patients treated with radiotherapy alone to evaluate survivin as a predictor for radiotherapy. One hundred two biopsy samples collected by endoscopy were immunostained by survivin antibody. Positive staining for survivin was obtained in 60.8% tumor samples. Survivin expression, metastasis, and clinical stage correlated significantly with overall survival. In multivariate analysis, survivin was an independent prognostic factor for predicting overall survival of patients with esophageal cancer. Moreover, in esophageal cancer cell lines, overexpression of survivin reduced the percentage of cell death induced by radiation. Our data indicate that survivin could be a potential predictor to define those patients with esophageal squamous carcinoma who would benefit from radiotherapy.

Differential up-regulation of survivin/BIRC5 in esophageal adenocarcinoma compared with normal squamous epithelium.

e14602 Background: Survivin, also known as BIRC5, inhibits apoptosis by interfering with caspase activation. High expression of survivin is seen in fetal tissues and various cancers. Published lite...

High survivin expression as a predictor of poor response to preoperative chemoradiotherapy in locally advanced rectal cancer

To evaluate seven molecular markers including cyclooxygenase -2, epidermal growth factor receptor, Ki-67, p21, survivin, thymidylate synthase, and vascular endothelial growth factor for prediction of response to preoperative chemoradiotherapy in locally advanced rectal cancer. Fifty-four patients with clinical T3-4 and/or node-positive rectal cancer who underwent preoperative chemoradiotherapy followed by surgical resection were enrolled into this study. Preoperative chemoradiotherapy consisted of 50.4 Gy of pelvic irradiation with concomitant 5-fluorouracil or oral capecitabine. Expression of molecular markers in pretreatment paraffin-embedded tumor biopsy specimens was assessed by immunohistochemical staining on the tissue microarray. Tumor downstaging was used as an endpoint for evaluation of tumor response. Tumor downstaging was observed in 22 patients (41%), and pathologic complete remission in 7 patients (13%). Among seven molecular markers, only survivin expression was significantly related with tumor downstaging: 26% with high survivin expression (>75% in extent) vs. 72% with low survivin expression (p = 0.0011). However, other six molecular markers were found not to have any correlation with tumor downstaging. High survivin expression in pretreatment tumor biopsy was associated with less tumor downstaging after preoperative chemoradiotherapy for locally advanced rectal cancer.

Prognostic value of survivin expression in parotid gland cancer in consideration of different histological subtypes

Background Cancer of the major salivary glands comprises a morphological diverse group of rare tumours of largely unknown cause. Survivin, an inhibitor of apoptosis has shown to be a significant prognostic indicator in various human cancers. The aim of this study was to assess the long-term prognostic value of survivin in a large group of histological different salivary gland cancers. Methods We analysed the survivin expression in 143 patients with parotid gland cancer by means of immunohistochemistry and tissue micro array. Survivin expression was categorised into a low and a high expressing group. The experimental findings were correlated with clinicopathological and survival parameters. The mean follow-up time was 54.8 months. Results A positive cytoplasmic expression of survivin was found in 61.5%, a high expression in 25.9% of all specimens. In the whole group, high cytoplasmic survivin expression significantly indicated a poor 5-year disease-free and overall survival rate ( p < 0.0001, p = 0.003). This applied for all adeno-, adenoid cystic and undifferentiated carcinomas whereas in mucoepidermoid carcinomas an analogical non-significant trend could be observed. A high cytoplasmic survivin expression significantly indicated a poor survival in high grade but not in low grade tumours. A multivariate analysis revealed that high cytoplasmic survivin expression was the only significant negative prognostic indicator for a poor 5-year disease-free survival rate in all patients ( p = 0.042). Conclusion The correlation between cytoplasmic survivin expression and survival probabilities of salivary gland cancer might make this an effective tool in patient follow-up, prognosis and targeted therapy in future.

Association of survivin expression following neoadjuvant radiochemotherapy in rectal cancer with distant metastases and survival.

483 Background: Valid molecular markers need to be implemented in clinical trials to fulfill the demand of a risk-adapted and more individualized multimodal therapy of locally advanced primary rectal cancer. In the present study the expression of the inhibitor-of-apoptosis (IAP) protein Survivin was evaluated in pre-treatment biopsies and corresponding post-treatment resection specimens, and was correlated to histo-pathological tumor characteristics and clinical follow-up. Methods: 116 patients with stage II/III rectal cancer treated with 5-FU-based neoadjuvant radiochemotherapy (RCT) within the German Rectal Cancer Trials were investigated. Survivin expression in pre-treatment biopsies and surgical resection specimens were determined by immunohistochemistry by two independent institutions and correlated with histopathologic parameters, tumor recurrences, disease-free and overall cancer-specific survival. Results: In pre-treatment biopsies, a higher Survivin expression correlated with advanced ypT (p=0.026) and ypUICC (p=0.05) stage as well as decreased disease-free survival (p=0.038) after preoperative RCT. High post-treatment Survivin levels were associated with advanced ypT stage (p=0.03) and residual lymph node metastases (p=0.04). Moreover, neoadjuvant RCT resulted in a significant down-regulation of Survivin expression (p &lt; 0.0001). A failure of RCT-induced down-regulation was associated with development of distant metastases (p=0.0056) and cancer-related death (p=0.026), and was significantly correlated with disease-free (p=0.011*/0.02**) and cancer-specific survival (p=0.0017*/0.01**) in uni*- and multivariate** analyses. Conclusions: Survivin expression displays a marker with prognostic validity in rectal cancers. These results underline the usefulness of Survivin to monitor individual response to RCT in rectal cancer, and encourage anti-Survivin strategies in multimodal rectal cancer therapy within future randomised clinical trials. No significant financial relationships to disclose.