High Nuclear Survivin Research Articles

Survivin, β-catenin, and ki-67 immunohistochemical expression in canine perivascular wall tumors: Preliminary assessment of prognostic significance.

High survivin expression has been correlated with poor outcomes in several canine tumors but not in soft tissue tumors (STTs). Survivin is a target gene of the Wnt/β-catenin pathway, which is involved in human STT oncogenesis. Immunohistochemistry for survivin, β-catenin, and Ki-67 was performed on 41 canine perivascular wall tumors (cPWTs), and statistical associations of protein expression and histopathologic and clinical variables with clinical outcomes were investigated. Immunohistochemically, there was nuclear positivity (0.9%-12.2% of tumor cells) for survivin in 41/41 (100%), cytoplasmic positivity (0 to > 75% of tumor cells) for survivin in 31/41 (76%), nuclear positivity (2.9%-67.2% of tumor cells) for β-catenin in 24/41 (59%), and cytoplasmic positivity (0% to > 75% of tumor cells) for β-catenin in 23/41 (56%) of cPWTs. All tumors expressed nuclear Ki-67 (2.2%-23.5%). In univariate analysis and multivariate analysis (UA and MA, respectively), every 1% increase of nuclear survivin was associated with an increase of the instantaneous death risk by a factor of 1.15 [hazard ratio (HR) = 1.15; P = .007]. Higher nuclear survivin was associated with grade II/III neoplasms (P = .043). Expression of cytoplasmic survivin, nuclear and cytoplasmic β-catenin, and nuclear Ki-67 were not significantly associated with prognosis in UA nor MA. Tumor size was a significant prognostic factor for local recurrence in UA [subdistribution HR (SDHR) = 1.19; P = .02] and for reduced overall survival time in MA. According to UA and MA, a unitary increase of mitotic count was associated with an increase of the instantaneous death risk by a factor of 1.05 (HR = 1.05; P = .014). Nuclear survivin, mitotic count, and tumor size seem to be potential prognostic factors for cPWTs. In addition, survivin and β-catenin may represent promising therapeutic targets for cPWTs.

Clinicopathological and Prognostic Value of Survivin Expression in Surgically Resected Pancreatic Ductal Adenocarcinoma.

Simple SummaryIn spite of recent optimisation of surgical therapy and multimodal treatment options, late diagnosis and devastating overall prognosis continue to characterise pancreatic cancer. The inhibitor of apoptosis protein survivin has been established as a relevant if not unambiguously understood factor in the formation and progression of pancreatic ductal adenocarcinoma (PDAC) being upregulated already in the early stages of tumourigenesis. Therefore, we analysed the expression of survivin in primary PDAC and lymph node metastases in an ample collective of 236 patients and demonstrated that cytoplasmic as nuclear overexpression of the protein correlated significantly with clinicopathological indicators of disease progression and, accordingly, showed prognostic relevance. The findings support the use of survivin as a biomarker to further explore the aggressiveness of PDAC subtypes and encourage its therapeutic approach as a molecular target to expand current chances for disease survival and potential cure.Background: Survival after surgery for pancreatic ductal adenocarcinoma (PDAC) remains poor. Thus, novel therapeutic concepts focus on the development of targeted therapies. In this context, inhibitor of apoptosis protein (IAP) survivin is regarded as a promising oncotherapeutic target. However, its expression and prognostic value in different tumour compartments of PDAC have not been studied. Methods: Immunohistochemical analysis of survivin in different PDAC tumour compartments from 236 consecutive patients was correlated with clinicopathological variables and survival. Results: In comparison to healthy pancreatic tissue high nuclear (p < 0.001) and high cytoplasmic (p < 0.01) survivin expression became evident in the tumour centre, along the invasion front and in lymph node metastases. Cytoplasmic overexpression of survivin in tumour centres was related to the presence of distant metastasis (p = 0.016) and UICC III/IV stages (p = 0.009), while high cytoplasmic expression at the invasion front grouped with venous infiltration (p = 0.022). Increased nuclear survivin along the invasion front correlated with perineural invasion (p = 0.035). High nuclear survivin in tumour centres represented an independent prognostic factor for overall survival of pancreatic tail carcinomas (HR 13.5 95%CI (1.4–129.7)) and correlated with a limited disease-free survival in PDAC (HR 1.80 95%CI (1.04–3.12)). Conclusion: Survivin is associated with advanced disease stages and poor prognosis. Therefore, survivin will help to identify patients with aggressive tumour phenotypes that could benefit from the inclusion in clinical trials incorporating survivin inhibitors in PDAC.

Survivin expression and impact on head and neck cancer outcomes.

Survivin is an inhibitor of apoptosis that is proposed as a target for anti-cancer therapy because of its high expression in cancer cells. It has potential as a prognostic and predictive biomarker of response to radiation and systemic therapies. We report its expression in head and neck squamous cell carcinoma (HNSCC) and its correlation with treatment response and survival. We measured survivin protein expression in tumor specimens from 96 patients with HNSCC treated at Fox Chase Cancer Center, of whom 21 were p16+. Quantitative automated immunofluorescence was employed to score nuclear and cytoplasmic survivin in 5 tissue microarrays (TMAs) consisting of 316 H&N tumor cores and 107 control tissue cores. Survivin levels were then correlated to therapy response and survival outcomes. Using the median score as the cutoff, overall survival (OS) was significantly shorter for the group expressing higher survivin in nuclear (p=0.013), cytoplasmic (p=0.018) and total compartments (p=0.006). No correlation was seen between survivin expression and patient sex or grade of tumor, T or N stage, or p16 status. Survivin expression in metastases did not significantly differ from that in primary tumors. Levels of p53 expression showed a significant positive correlation with higher survivin expression in the cytoplasm (p=0.0264) and total compartments (p=0.0264), but not in the nucleus (p=0.0729). Survivin expression above the median is associated with shorter overall survival in HNSCC, including for patients treated with chemotherapy or radiation. p16 expression did not correlate with survivin levels.

P53 expression and subcellular survivin localization improve the diagnosis and prognosis of patients with diffuse astrocytic tumors.

Diffuse astrocytic tumors are the most frequently occurring primary central nervous system (CNS) tumors. Their histological sub-classification into diffuse astrocytoma (DA), anaplastic astrocytoma (AA) and glioblastoma (GB) is challenging and the available prognostic factors are limited to age and tumor subtype. Biomarkers that may improve the histological sub-classification and/or serve as prognostic factors are, therefore, urgently needed. The relationship between survivin and p53 in diffuse astrocytic tumor progression and survival is currently unclear. Here, we aimed to assess the relevance of these proteins in the accuracy of the histological sub-classification of these tumors and their respective treatment responses. One hundred and thirty-three formalin-fixed paraffin-embedded diffuse astrocytic tumor samples were included. The tumor samples were histologically reviewed and subsequently assessed for p53 and survivin expression and the presence of the IDH R132H mutation by immunohistochemistry. p53 expression levels and survivin subcellular localization patterns were correlated with histological classification and clinical outcome. We found that age and histological subtype were the only features with a prognostic impact. In addition, we found that high p53 expression levels and a nuclear survivin localization correlated with the AA subtype, whereas cytoplasmic survivin localization correlated with the GB subtype. We also found that patients carrying tumors with a high cytoplasmic survivin expression, a high nuclear survivin expression or a high p53 expression, and who did not receive radiotherapy, exhibited poorer short-term and long-term overall survival rates. Our data suggest that subcellular survivin localization and p53 expression may be employed as valuable tools to improve the accuracy of the histological sub-classification of diffuse astrocytic tumors. Patients whose tumors overexpress these proteins may benefit from radiotherapy, irrespective age and/or histological classification.

Abstract B66: P53 expression and survivin subcellular localization contribute to the diagnosis and prognosis of patients with astrocytomas

Abstract Astrocytomas are the most frequent subtype of primary central nervous system (CNS) tumors. Diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III) and glioblastoma (GB–grade IV) are diffuse infiltrating astrocytomas derived from glial cells or precursors. Despite continuous efforts from the scientific community, these tumors still have a poor prognosis. Histologic grading is still challenging, and prognostic factors are still limited to age and tumor grade. Biomarkers that could improve histologic grading, especially that could help differentiate grade III from the other subtypes, and/or serve as prognostic factors are much needed. Furthermore, the relationship between survivin and p53 in astrocytoma progression and survival is still controversial. The present study aims to investigate the role of these proteins in the accuracy of histologic grading of diffuse astrocytic tumors and treatment response. One hundred thirty-five formalin-fixed, paraffin-embedded astrocytoma samples were obtained from patients. Tumor samples were reviewed and stained for survivin and p53 by immunohistochemistry, and the staining levels and survivin subcellular localization were correlated with histologic grading and patient outcomes. Age and histologic grade were the only clinical features that had a prognostic impact. High nuclear survivin and p53 correlated with grade III astrocytomas. High cytoplasmic survivin correlated with GB. Furthermore, patients whose tumors expressed high cytoplasmic survivin, high nuclear surviving, or high p53 and did not receive radiotherapy had worse short-term and long-term survival. Our results suggest that survivin subcellular localization and p53 expression improve the accuracy of histologic grading. Patients whose tumors overexpress these proteins benefit from radiotherapy regardless of age and histologic grade. Furthermore, patients whose tumors overexpress survivin may benefit from novel targeted antisurvivin treatment. Citation Format: Roberta Soares Faccion*, Paula Sabbo Bernardo*, Giselle Pinto de Faria Lopes*, Leonardo Soares Bastos, Cristina Lordello Teixeira, José Antonio de Oliveira, Priscila Valverde Fernades, Luiz Gustavo Dubois, Leila Maria Chimelli, Raquel Ciuvalschi Maia. P53 expression and survivin subcellular localization contribute to the diagnosis and prognosis of patients with astrocytomas [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B66.

Low Merlin expression and high Survivin labeling index are indicators for poor prognosis in patients with malignant pleural mesothelioma

IntroductionAlterations of the tumor suppressor Neurofibromatosis type II (NF2) have been reported in about 40% of Malignant pleural mesothelioma (MPM) patients. NF2 (Merlin) deficiency leads to alterations of the Hippo pathway; resulting in activation of the oncogenic Yes Associated Protein-1 (YAP1). Our aim was to investigate the association between these alterations and clinical outcomes. Material and methodsTissue microarrays composed of MPM tumors derived from 2 independent MPM cohorts were employed for this study. Immunohistochemical expression of Merlin, YAP1 and its target genes, Survivin and connective tissue growth factor (CTGF) were assessed in nuclear and cytoplasmic fractions. Cohort 1 was comprised of 145 patients intended to be treated with chemotherapy (CTX) followed by extrapleural pneumonectomy (EPP), thus both pre- and post-CTX tissues were available. Cohort 2 was comprised of 59 patients treated with EPP followed by intraoperative hyperthermic cisplatin and/or adjuvant CTX and/or radiotherapy. Marker expression was quantified by means of labeling index (%) for nuclear Survivin and by H-score for the other markers. The dichotomized marker expression was tested for the association with overall survival (OS) and freedom from recurrence (FFR). ResultsKaplan–Meier survival curves revealed a significant association between low cytoplasmic Merlin expression in pre-induction CTX tissues of cohort 1 with shorter FFR (p = 0.02) and OS (p = 0.03). The same tendency was observed in the chemotherapy naïve tissues obtained during EPP of cohort 2. Low nuclear Merlin expression in post-CTX tissues (available from cohort 1 only) was associated with shorter FFR (p = 0.04) and OS (p = 0.05). High nuclear Survivin labeling indices in both pre- and post-CTX tissues of cohort 1 was associated with shorter FFR (p = 0.02). In cohort 2, this was associated with both FFR and OS (p = 0.046 and p = 0.002, respectively). In multivariate analysis, low expression of cytoplasmic Merlin remained an independent prognosticator for shorter FFR of cohort 1 [hazard ratio (HR) = 0.5, 95% confidence interval (CI) = 0.3–0.9, p = 0.001] and OS [HR = 0.5, 95% CI = 0.3–1, p = 0.04]. High Survivin labeling index was an independent prognostic factor for shorter FFR in patients from cohort 1 [HR = 3.4, 95% CI = 1.7–6.8, p = 0.006] and shorter OS in patients from cohort 2 [HR = 2.35, 95% CI = 1.27–4.33, p = 0.006]. ConclusionsOur findings uncover the significance of Merlin protein expression and Survivin labeling index as prognosticators for poor clinical outcome in two independent MPM cohorts. If confirmed, these markers may be used to identify subgroups of patients benefitting from additional treatment.

Adenoid cystic carcinoma of the lacrimal gland: role of nuclear survivin (BIRC5) as a prognostic marker

This study aimed to evaluate the expression of nuclear survivin in adenoid cystic carcinoma (ACC) of the lacrimal gland and to determine if this expression is associated with histopathological features, markers of apoptosis and proliferation or clinical outcomes. Immunohistochemical staining for survivin, p53, Ki-67 and Bcl-2 was analyzed in 55 cases of ACC of lacrimal gland. Thirty-one cases (56.3%) expressed nuclear survivin. All cases expressed p53, Ki-67 and Bcl-2. Eleven cases (35.5%) had a high nuclear survivin score (NS-SCORE) and 20 cases (64.5%) had a low NS-SCORE. Cases with a high NS-SCORE had a shorter progression-free survival (PFS) (P < 0.0001), higher expression of Ki-67 (P < 0.005) and a solid tumour pattern >30% (P < 0.005). Nuclear expression of survivin impacts prognosis significantly and is thus a promising prognostic marker in ACC of the lacrimal gland.

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.

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

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.

Tumor survivin expression in locally advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemoradiation followed by surgical resection

7595 Background: Recently tumor molecular markers have shown promise as prognostic and predictive indicators for survival in early and advanced stage NSCLC patients (pts.) treated with chemotherapy. The objective of this study was to correlate immunohistochemistry (IHC) markers of pre-treatment biopsies in locally advanced NSCLC patients treated with concurrent platinum based chemoradiation followed by surgical resection. Methods: This is a retrospective study that included stage III NSCLC pts who had adequate pre-treatment tumor specimens and were treated with platinum based chemotherapy regimens and concurrent thoracic radiation (40 Gy). Thirty three pts had sufficient pre-treatment tissue for IHC and were identified from a surgical database. Cells were stained by IHC for frequency (0–4) and intensity (0–4) of ERCC1, PTEN, and survivin and analyzed by log-rank and multivariate Cox PH regression for potential relationships to pathologic complete response (pCR), time to recurrence (TTR), and overall survival (OS). Results: Characteristics of 33 pts: 15 females; median age 61; 17 adenocarcinoma, 10 squamous(sq), 5 undifferentiated, 1 adeno-sq. Median OS was 23 months (mo) (5.9–140), and median TTR was 14.7 mo (3.5–121). Following chemoradiation, 9 patients had pCR. pCR was associated with improved TTR, p &lt; .027. ERCC1 and PTEN were not significantly related to OS, TTR, or pCR. High nuclear survivin frequency (&gt;2) was associated with worse OS, HR 0.4, p&lt; .045 and lower nuclear survivin intensity (&lt;4) was marginally associated with pCR, p&lt; .10. Conclusions: In this exploratory analysis, higher survivin expression was associated with worse prognosis in locally advanced NSCLC patients treated with chemoradiation followed by surgery. These results suggest that additional studies of survivin are warranted in NSCLC and that adding survivin inhibitors to chemoradiation is a reasonable strategy for locally advanced NSCLC with high survivin expression. No significant financial relationships to disclose.

The Prognostic Significance of Survivin Expression in Breast Cancer

Purpose: Survivin is a member of the inhibitors of apoptosis family. It has recently comes into the limelight as a promising tumor marker, but many previous reports have shown controversial results regarding the significance and prognostic value of a survivin expression. In this study we determined the correlation between the survivin expression and the conventional prognostic markers and we also investigated the outcomes according to the localization of the survivin expression. Methods: Tissue microarray (TMA) blocks were made with formalin-fixed paraffin-embedded tissues from 185 breast cancer patients and the immunohistochemical staining was done using an anti-survivin antibody. Among these, 157 patients were available for a survivin expression. The conventional clinicopathologic features and overall survival were correlated with the localization of the survivin expression. Results: Survivin was expressed in 101 breast cancers (64.3%). A higher cytoplasmic survivin expression were noted in the older group (p=0.003), in the node-negative cancers (p= 0.012), in the earlier tumor stages (p=0.012) and in the cancers that had not been treated with adjuvant chemotherapy (p=0.014). On the contrary, a higher nuclear survivin expression was inversely correlated with an estrogen expression (p=0.006) and a progesterone receptor (p=0.043) expression. In terms of survival, a cytoplasmic expression was associated with improved overall survival (p=0.01) but a nuclear survivin expression was correlated with unfavorable overall survival (p=0.002). A high cytoplasmic to nuclear ratio of survivin was associated with improved overall survival (p=0.001) conversely, increased nuclear to cytoplasmic survivin ratio was correlated with unfavorable overall survival (p<0.0001). Multivariate analysis revealed that nuclear survivin expression (p= 0.001) and high nuclear to cytoplasmic survivin ratio (p=0.012) were independent predictor of overall survival. Conclusion: Survivin is frequently expressed in primary breast cancer. A cytoplasmic survivin expression is a good prognostic predictor for patients with axillary node negative early breast cancers and a nuclear survivin expression is a worse independent predictor of overall survival for patients with axillary node positive breast cancers.

Prognostic Significance of the Epstein-Barr Virus, p53, Bcl-2, and Survivin in Nasopharyngeal Cancer

Nasopharyngeal cancer (NPC) is a malignant epithelial carcinoma which is intimately associated with EBV. The latent presence of EBV affects the function of p53, Bcl-2, and survivin. We thus investigated the relationship between EBV status, p53, Bcl-2, and survivin in biopsy specimens from patients with primary NPC. Archival formalin-fixed, paraffin-embedded NPC biopsies were evaluated in 80 patients treated with curative radiation from a single institution. The presence of EBV was determined using EBER in situ hybridization, whereas p53, Bcl-2, and survivin were assessed using immunohistochemistry. The majority of NPC specimens in this patient cohort were EBER-positive (64 of 78, or 82%), which in turn, was significantly associated with ethnicity (P = 0.0007), and WHO subtype 2A/2B (P = 0.04). EBER-positive tumors were also associated with p53 (P = 0.002), Bcl-2 (P = 0.04), and nuclear survivin (P = 0.03) expression. Patients with EBER-positive NPC fared better, with a 10-year overall survival of 68% versus 48% for EBER-negative patients (P = 0.03). For nuclear survivin, patients with either low or high nuclear survivin fared worse than patients with intermediate survivin expression (P = 0.05), suggesting that there is an optimal proportion of survivin-expressing cells for best function and clinical outcome. With an extended median follow-up time of 11.4 years, EBV status remains a strong predictor for overall survival in NPC. EBV-positive NPC has strong molecular associations with p53, Bcl-2, and survivin expression. Furthermore, we provide clinical data revealing the potentially dual nature of survivin in predicting clinical outcome.

Nuclear and cytoplasmic expression of survivin in 67 surgically resected pancreatic cancer patients

Pancreatic cancer is one of the most aggressive gastrointestinal cancer with less than 10% long-term survivors. The apoptotic pathway deregulation is a postulated mechanism of carcinogenesis of this tumour. The present study investigated the prognostic role of apoptosis and apoptosis-involved proteins in a series of surgically resected pancreatic cancer patients. All patients affected by pancreatic adenocarcinoma and treated with surgical resection from 1988 to 2003 were considered for the study. Patients' clinical data and pathological tumour features were recorded. Survivin and Cox-2 expression were evaluated by immunohistochemical staining. Apoptotic cells were identified using the TUNEL method. Tumour specimen of 67 resected patients was included in the study. By univariate analysis, survival was influenced by Survivin overexpression. The nuclear Survivin overexpression was associated with better prognosis (P=0.0009), while its cytoplasmic overexpression resulted a negative prognostic factor (P=0.0127). Also, the apoptotic index was a statistically significant prognostic factor in a univariate model (P=0.0142). By a multivariate Cox regression analysis, both the nuclear (P=0.002) and cytoplasmic (P=0.040) Survivin overexpression maintained the prognostic statistical value. This is the first study reporting a statistical significant prognostic relevance of nuclear and cytoplasmic Survivin overexpression in pancreatic cancer. In particular, patients with high nuclear Survivin staining showed a longer survival, whereas patients with high cytoplasmic Survivin staining had a shorter overall survival.