Expression Pattern Of Survivin Research Articles

Survivin as a potential biomarker for early diagnosis of the progression of precancerous lesions to gastric cancer.

Gastric cancer is a common cancer developed in a carcinogenesis process from precancerous lesions including chronic gastritis, intestinal metaplasia, and dysplasia. Survivin, an inhibitor-of-apoptosis protein, is associated with the initiation and progression of gastric cancer. The present study aimed to evaluate the immunohistochemical expression patterns of survivin and its relationship with early diagnosis of gastric cancer in Iranian patients. In this retrospective case-control study, immunoexpression of survivin was investigated on sections obtained from formalin-fixed paraffin-embedded tissue blocks of 38 chronic gastritis, 32 intestinal metaplasia, 20 dysplasia, 28 gastric adenocarcinoma, and 22 controls. Survivin immunoexpression in chronic gastritis was higher than controls, but this difference was not statistically significant (P > 0.05). However, survivin immunoexpression had a steady significant increase from control and chronic gastritis to intestinal metaplasia to dysplasia to gastric adenocarcinoma (P < 0.05). Sensitivity, specificity, and area under the curve of survivin immunohistochemical test for the diagnosis of gastric cancer were 87.5%, 74.4%, and 0.85, respectively. Males had a significantly higher survivin expression than females (P < 0.001). Also, survivin expression was significantly higher in older patients than in younger ones (P < 0.001). It seems that the steady increase in survivin expression from different precancerous lesions to gastric adenocarcinoma suggests that survivin can be used as a potential biomarker for the prevention and early diagnosis of gastric cancer.

Expression of anti - Apoptotic survivin in odontogenic keratocyst, adenomatoid odontogenic tumor and ameloblastoma.

The process of odontogenesis is complex involving epithelial-mesenchymal interactions, along with the molecular signalling pathways triggering the initiating process. The triggering factors and cells precisely involved in the pathogenesis of odontogenic cysts and tumors are unknown. There is a vast array of biomarkers used to stain different sites, thereby helpful in diagnosing and evaluating the prognosis of these cysts and tumors. In the following study, Anti Apoptotic survivin expression patterns were assessed quantitatively in 48 samples (12 each) of Reduced Enamel Epithelium, Adenomatoid Odontogenic Tumor, Odontogenic Keratocyst and Ameloblastoma. The Aim of this study is to assess the anti-apoptotic survivin expression in Reduced Enamel Epithelium, Adenomatoid odontogenic tumour, Odontogenic Keratocyst and Ameloblastoma. The present study is carried out with 12 samples in each group. Routine hematoxylin and eosin staining was performed for confirmatory diagnosis. Later Immunohistochemistry was performed using survivin antibody. Survivin protein expression was analyzed using the parameters like location, intensity, percentage of cells positivity with survivin protein and extent of staining. With the help of Olympus BX 43 microscope, with ProgRes microscope camera, the 48 slides obtained were examined. The region of interest was selected in each slide and number of cells positively stained was counted. Data was analyzed using SPSS software version 23. Descriptive for scale data, results were analysed by using ANOVA with Chi-square test for intergroup comparison. The results showed significant P value <0.05. Expression of survivin was highest in Ameloblastoma, followed by Odontogenic keratocyst, Adenomatoid odontogenic tumor, and Reduced Enamel Epithelium. Survivin was involved in the inhibition of apoptosis as well as the detailed understanding of the biological behaviour of odontogenic cysts and tumours, thereby increasing therapeutic approaches.

Clinical Features and Expression Patterns for Burn Patients Developed Marjolin Ulcer.

Marjolin's ulcer is a type of skin cancer that generated from chronic nonhealing trauma. For years, its pathogenesis mechanisms remain unclear. Regarding this situation, the authors retrospectively analyze the patients admitted to their department from 2005 to 2019 to present several representative cases and examine the expression patterns of survivin and its role in this process. Among these patients, the latent period ranges from 2 to 25 years, with 8.43 years in average. There is no notable relationship between the latent period and age (P = .643 > .05). Therefore, Marjolijn's ulcer arises from extremities and joints more often compared with other parts (P < .05). The expression ratio of survivin in Marjolin's ulcer is significantly higher than that in skin ulcer (P < 0.05). And the expression ratio of survivin in patients diagnosed with Marjolin's ulcer is also correlated with lymphatic metastasis (P < .05). Frequent follow-ups and prompt diagnosis and management are necessary as the prognosis is poor for patients with metastasis. Survivin may be a potential target for future development of target therapy in order to maximize the efficacy and improve the quality of life for patients suffering from Marjolin's ulcer.

Survivin expression pattern in the intestine of normoxic and ischemic rats

BackgroundSurvivin, a member of the inhibitor of apoptosis protein (IAP) family, regulates mitosis and chromosome segregation. The expression of survivin proceeds during embryonic development and in addition has already been demonstrated in cancer cells. However, there is also evidence of survivin expression in differentiated tissues, including the gastro-intestinal tract of adult rats. A study with human colon specimens exhibited survivin in most basal crypt epithelial cells of normal mucosa. There is rather limited information on survivin expression in the small intestine. In order to paint a more detailed and thus complete picture of survivin expression patterns in the gastrointestinal tract, we used an immunohistochemical approach in normal adult rat small intestinal and ascending colonic tissue. Moreover, to get deeper insights in the regulation of survivin expression after tissue damage, we also studied its expression in mesenteric ischemia-reperfusion (I/R) injury.MethodsMesenteric ischemia-reperfusion injury was induced in male Wistar rats (six animals/group) by occlusion of the superior mesenteric artery for 90 min and subsequent reperfusion for 120 min. Paraffin sections of untreated or ischemically treated tissue were assessed immunohistochemically by survivin and Ki-67 staining.ResultsSurvivin could be detected in the small intestine and ascending colon of the normoxia group. It was expressed mainly in the epithelial cells of the crypts and only marginally in the villi. The individual small intestinal segments studied revealed comparable staining intensities. Likewise, expression of survivin was detected in the ischemically damaged small intestine and ascending colon. The expression pattern corresponded to the normoxic animals, as far as verifiable due to the existing tissue damage. Comparison of the expression pattern of Ki-67, a protein that acts as a cellular marker for proliferation, and survivin demonstrated a coincidental localization of the two proteins in the small intestinal and ascending colonic tissue.ConclusionsSurvivin was expressed strongly in epithelial cells of small intestinal as well as ascending colonic tissue. Its expression was located in cells with a high proliferation rate and regenerative capacity. This further supports the decisive role of survivin in cell division. Surprisingly, the ischemically damaged small intestinal and ascending colonic tissue showed a comparably high expression level. These results suggest that there is already a maximal survivin expression under normal conditions. However, the intestine is able to maintain the regenerative capacity even in spite of an ischemic injury. These findings reflect the important relevance of an intact intestinal barrier.

Survivin: a unique target for tumor therapy.

Survivin is the smallest member of the Inhibitor of apoptosis (IAP) family of proteins, involved in inhibition of apoptosis and regulation of cell cycle. These functional attributes make Survivin a unique protein exhibiting divergent functions i.e. regulating cell proliferation and cell death. Expression pattern of Survivin is also distinctive; it is prominently expressed during embryonal development, absent in most normal, terminally differentiated tissues but upregulated in a variety of human cancers. Expression of Survivin in tumours correlates with not only inhibition of apoptosis and a decreased rate of cell death, but also resistance to chemotherapy and aggressiveness of tumours. Therefore, Survivin is an important target for cancer vaccines and therapeutics. Survivin has also been found to be prominently expressed on both human and embryonic stem cells and many somatic stem cell types indicating its yet unexplored role in stem cell generation and maintenance. Overall, Survivin emerges as a molecule with much wider role in cellular homeostasis. This review will discuss various aspects of Survivin biology and its role in regulation of apoptosis, cell division, chemo-resistance and tumour progression. Various molecular and immunotherapeutic approaches targeting Survivin will also be discussed.

Sodium phenylbutyrate antagonizes prostate cancer through the induction of apoptosis and attenuation of cell viability and migration.

BackgroundProstate cancer (PCa) is a leading cause of cancer-related death in men. Sodium phenylbutyrate (SPB) has shown its potential as an anticancer therapy in numerous cancer types. In the present study, we attempted to assess the effect of SPB against PCa and whether this treatment was associated with the regulation of survivin.MethodsTwo human PCa cancer cell lines, DU145 and PC3, were used in the present study. Cell Counting Kit-8 (CCK-8) assay was conducted to measure the proliferation of PCa cells incubated with SPB. The effect of SPB on the cell apoptosis, cell colony formation ability, and cell morphological change was also assessed. Transwell experiment and Western blotting assay were performed to determine the effect of SPB on the migration and invasion ability of both cell types. Moreover, the expression pattern of survivin and MAPK members in both cell types after the treatment of SPB was also detected. Additionally, an in vivo tumor formation assay was performed to evaluate the treatment potential of SPB against PCa.ResultsWe found that the viability of PCa cells was significantly inhibited by SPB treatment. As illustrated by flow cytometry, for DU145 cell line the average apoptotic rate of SPB-treated cells was significantly lower than that of the control group (P<0.05); similar results were also seen for PC3 (P<0.05). SPB administration also attenuated the colony formation and migration abilities in both cell lines. The expression level of survivin in SPB-treated cells was significantly downregulated, while the phosphorylation of p-38 and ERK was enhanced. Furthermore, in vivo tumor formation of both cell lines was suppressed by SPB as well.ConclusionThe above results confirmed the potential of SPB as an effective therapeutic agent for the prevention or treatment of PCa. This amelioration might be due to the blockade of the survivin pathway.

Targeting Survivin Enhances Chemosensitivity in Retinoblastoma Cells and Orthotopic Tumors.

Treatments for retinoblastoma (Rb) vary depending on the size and location of the intraocular lesions and include chemotherapy and radiation therapy. We examined whether agents used to treat Rb induce a pro-survival phenotype associated with increased expression of survivin, a member of the inhibitor of apoptosis family of proteins. We document that exposure to carboplatin, topotecan or radiation resulted in elevated expression of survivin in two human Rb cell lines but not in normal retinal pigmented epithelial (RPE) cells. Cellular levels of survivin were attenuated in Rb cells exposed to an imidazolium-based survivin suppressant, Sepantronium bromide (YM155). Protein expression patterns of survivin in RPE cells were not altered following treatment protocols involving exposure to YM155. Including YM155 with chemotherapy or radiation increased levels of apoptosis in Rb cells but not in RPE cells. Intraocular luciferase expressing Rb tumors were generated from the Rb cell lines and used to evaluate the effects of carboplatin and YM155 on in-vivo survivin expression and tumor growth. Carboplatin induced expression of survivin while carboplatin combined with YM155 reduced survivin expression in tumor bearing eyes. The combination protocol was also most effective in reducing the rate of tumor regrowth. These results indicate that targeted inhibition of the anti-apoptotic protein survivin provides a therapeutic advantage for Rb cells and tumors treated with chemotherapy.

Expression and clinicopathological significance of antiapoptotis protein survivin in gallbladder cancer

Clinical significance of survivin (antiapoptosis protein) in gallbladder cancer is not yet established. This study was performed to assess the expression pattern of survivin in benign and malignant gallbladder lesions using immunohistochemistry (IHC), and to assess its clinicopathological significance. Prospective study from July 2012 to July 2014 was performed as a part of intramural research project. Tissue samples from resected gallbladder for cholelithiasis (n = 27) and carcinoma gallbladder (n= 24) were evaluated for survivin expression by IHC using a scoring system. Their expression was correlated with different clinicopathological parameters. Fisher's exact test, Student's t-test, and Chi-square test were used as appropriate for data analysis. Kaplan-Meier methods were used to calculate overall and disease-free survival rates among different groups. Two-sided P< 0.05 was considered as significant. Benign group (19 females, age [mean ± standard deviation [SD] 45 ± 14 years) and malignant group (20 females, age [mean ± SD] 48.9 ± 13.4 years) were comparable with respect to menopausal status, presence, size and types of stones. However, survivin expression was significantly higher (66.7%, 95% confidence interval [CI] 24-75) in gallbladder cancer than in cholelithiasis group (33%, CI 46-83), P= 0.025). Its expression did not correlate with gender, age, menopausal status, presence of gallstones or their size, number and type, tumor differentiation, and tumor stage. Significantly higher expression of survivin protein in gallbladder cancer as compared to cholelithiasis group suggests its role in gallbladder carcinogenesis though it may not have prognostic value.

Epidermal growth factor enhances the developmental competence of yak (Bos grunniens) preimplantation embryos by modulating the expression of survivin and HSP70

Culture conditions can affect cleavage, zygotic genome activation, embryonic development, and blastocyst quality. Epidermal growth factor (EGF) has important autocrine and/or paracrine effects during early embryonic development. However, few studies of the effect of EGF on yak embryos have been reported. The aim of this study was to determine the effects of exogenous EGF on yak embryonic development in vitro, as well as the correlation between HSP70 and survivin expression patterns, blastocyst quality and EGF concentration. The in vitro matured cumulus–oocyte complexes (COCs) were fertilized with frozen–thawed semen, and the zygotes were incubated in culture media supplemented with different concentrations of EGF. During in vitro culture, the embryos were analyzed for development to the 4-cell, 8-cell, 16-cell, and blastocyst stages. The variation in total blastocyst cell numbers and their allocation to the inner cell mass (ICM) and trophectoderm (TE) lineages were determined by differential CDX2 staining. Relative HSP70 and survivin mRNA expression was examined by qPCR at the blastocyst stage. Compared to the control, EGF treatment (100ng/mL) significantly increased the blastocyst formation rate but had no significant effect at other stages. The total number of cells per blastocyst increased with 100ng/mL of EGF. HSP70 and survivin expression was higher in the EGF treatment groups than in the control group and highest with 100ng/mL EGF. From the present study, we conclude that EGF significantly enhances yak blastocyst formation and cell numbers, which might be associated with the increased expression of HSP70 and survivin after EGF treatment.

Expression Analysis of Aurora-C and Survivin, Two Testis-Specific Genes, in Patients with Colorectal Cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. The high frequency of positive families shows the importance of public awareness and screening strategies in those families. Cancer/testis (CT) antigens such as Aurora-C and Survivin are a group of antigens expressed in various tumor types of human cancers. Therefore, the aim of this study was to investigate the expression of Aurora-C and Survivin genes in malignant and normal tissues and their correlation to clinicopathological characteristics. Tumor samples were obtained from 33 patients and adjacent non-tumorous tissues from 7 patients were also used as control. Patients were diagnosed with various stages of colorectal cancer. The level of Aurora-C and Survivin genes were evaluated by using real-time quantitative Polymerase Chain Reaction. The expression pattern of Survivin and Aurora-C revealed significant changes in tumor tissues when compared with normal tissues (p < 0.05). Also, these expressions were associated with the grade of disease and tumor size. There was no significant relationship between the expression of Survivin and Aurora-C genes (p > 0.05). In conclusion, the overexpression of Aurora-C and Survivin genes may play an important role in the development of colorectal cancer and may play a potential role in cancer therapy.

Non-Invasive Exploration of Neonatal Gastric Epithelium by Using Exfoliated Epithelial Cells

Background & AimsIn preterm infants, exfoliated gastric epithelial cells can be retrieved from aspirates sampled through the naso-gastric feeding tube. Our aims were to determine (1) whether the recovery of exfoliated cells is feasible at any time from birth through the removal of the nasogastric tube, (2) whether they can be grown in culture in vitro, and (3) whether the physiological state of exfoliated cells expressing H+/K+ -ATPases reflects that of their counterparts remaining in situ at the surface of the gastric epithelium in neonatal rat pups.MethodsIn infants, gastric fluid aspirates were collected weekly after birth or every 3 hours over 24-h periods, and related to clinical parameters (Biocollection PROG/09/18). In rat pups submitted to a single fasting/refeeding cycle, we explored circadian exfoliation with the cellular counter-parts in the gland. All samples were analyzed by confocal imaging and Enzyme-Linked Immunosorbent Assay.ResultsEpithelial cells were identified by microscopy using membrane-bound anti-H+/K+ ATPases antibody, assessed for nucleus integrity, and the expression of selected proteins (autophagy, circadian clock). On 34 infants, the H+/K+ -ATPase-positive cells were consistently found quiescent, regardless of gestational age and feeding schedule from day-5 of life to the day of removal of the naso-gastric tube. By logistic regression analysis, we did find a positive correlation between the intensity of exfoliation (cellular loss per sample) and the postnatal age (p<0.001). The H+/K+ ATPase-positive cells established in culture retained the expression of a biomarker of progenitor status (Pouf5F1-Oct4). In rat pups, the expression pattern of Survivin in H+/K+ ATPase-positive exfoliated cells paralleled that observed in cells remaining at the surface of the gastric gland.ConclusionsTracking parietal cells can improve clinical monitoring and understanding of the autophagic death via the phosphatidylinositol 3-kinase/Akt/survivin pathway.

Survivin expression patterns could reflect different roles in hepatocarcinogenesis, especially in non‐alcoholic fatty liver disease‐related hepatocellular carcinoma

Survivin expression patterns could reflect different roles in hepatocarcinogenesis, especially in non‐alcoholic fatty liver disease‐related hepatocellular carcinoma

Survivin mediates prostate cell protection by HIF‐1α against zinc toxicity

The prostate contains extremely high concentrations of zinc, but survives and grows without apparent injury. This begs the question as to how prostate cells avoid the toxic effects of zinc. In a previous study, the authors found that; HIF-1alpha is expressed concomitantly with the accumulation of zinc in the epithelial cells of normal rat prostates, the zinc ion stabilizes HIF-1alpha in prostate cells, and that HIF-1alpha protects prostate cells from zinc toxicity. In the present study, the authors addressed the mechanism responsible for the protective effect of HIF-1alpha in a high zinc environment. Immunofluorescent staining, immunoblotting, reverse transcription-polymerase chain reaction, reporter assay, and cell cycle analysis. Survivin was induced by ZnCl(2) in a HIF-1 dependent manner in both DU-145 and PNT2 prostate cells. Furthermore, HIF-1 induced survivin expression at the transcriptional level and the induction of survivin was abolished by HIF-1alpha knock-down. In addition, HIF-1-dependent survivin overexpression promoted prostrate cell survival and prevented cell arrest in the presence of high zinc concentrations, and si-survivin transfected cells under zinc rich conditions contained markedly higher levels of cleaved caspase-9 and PARP than si-con transfected cells. Finally, survivin expression patterns well matched rat prostate proliferation statuses. Under zinc rich conditions, prostate epithelial cells HIF-1-dependently express survivin, which promotes prostate cell proliferation, and prevents apoptosis and cell cycle arrest. Accordingly, the HIF-1alpha-survivin pathway appears to facilitate prostate cell survival and growth in zinc rich environments, and this pathway could be a therapeutic target for the treatment of prostate hyperplasia.

Expression patterns of survivin and cuspuse-3 in dissymmetric enlarged prostate

Objective To compare the different expression patterns of survivin and caspase-3 between the larger part and the smaller part of the dissymmetric enlarged prostates in BPH patients, and to clarify the role of apoptosis in BPH etiology. Methods BPH tissues from 25 patients were embedded in paraffin. The specimens constituted of two prostate parts from each patient. One part was from the larger enlarged gland and the other was from the smaller enlarged counterpart. 50 paraf-fin blocks were cut into sections and stained with survivin and caspase-3 polyclonal antibodies against human. All the data was analyzed by SPSS13.0 software. Results Survivin immunoreactivity was localized in prostatic cell nuclei. Survivin expression in larger enlarged parts (22.08±16. 33)0% was significantly higher than the smaller parts (7. 645±5. 45)%(P 0. 05). Conclusions Survivin and caspase-3 expression patterns are different in the two parts of the dissymmetric enlarged prostates. These different patterns indicate apoptosis playing an important role in BPH development. Key words: Benign prostatic hyperplasia (BPH); Apoptosis; Survivin; Caspase-3

Expression of survivin and its spliced variants in bladder tumors as a potential prognostic marker.

Survivin, a novel inhibitor of apoptosis, is re-expressed in a vast majority of human cancers and is widely considered as a diagnostic marker of cancers. Survivin protein regulates both cell division and apoptosis. There are at least 5 spliced variants of the gene with different subcellular localization and anti-apoptotic property. We examined the expression pattern of survivin and its 2 spliced variants, survivin-deltaEx3 and survivin-2B, and their prognostic values in archival collections of formalin-fixed paraffin-embedded samples of bladder tumors. Total RNA from formalin-fixed paraffin-embedded samples (51 samples from 30 patients with bladder cancer and 5-year follow-up) were extracted and analyzed by semiquantitative reverse transcriptase polymerase chain reaction technique. Tissue distribution and subcellular localization of survivin protein in tumor tissues was also examined by immunohistochemistry. The expression of survivin, survivin-deltaEx3, and survivin-2B were detected in 66.6%, 47.8%, and 54.7% of the specimens, respectively. The expression of survivin and survivin-deltaEx3 were preferentially elevated in tumors with higher grades, whereas survivin-2B expression was lower in high-grade tumors (P = .04). A reverse correlation was observed between survivin-2B expression and high-grade tumors. Immunohistochemistry results also confirmed the nuclear localization of survivin protein within tumoral cells. We were successful in detecting the expression of survivin and its variants in formalin-fixed paraffin-embedded bladder samples. Furthermore, our results showed that overexpression of survivin and survivin-deltaEx3 in bladder tumors correlates with poor prognosis of bladder cancer. We suggest that survivin and its variants are suitable prognostic markers of bladder tumors.

Differential expression of survivin and its splice variants, survivin-ΔEx3 and survivin-2B, in bladder cancer

Background: Survivin, an inhibitor of apoptosis protein (IAP), has been regarded as a valuable tumor marker for diagnosis and prognosis of bladder cancer. Recently, three splice variants of the gene with different anti-apoptotic activities have been reported. However, there is no data on the expression and potential causative roles of these transcripts in bladder cancer. Here, we have investigated the expression pattern of survivin and two of its splice variants, survivin-ΔEx3 and survivin-2B, in malignant versus non-malignant bladder tissues. Methods: We used semi-quantitative RT-PCR analysis to examine the expression of survivin variants in 30 transitional cell carcinoma, 19 matched non-tumor, and 9 apparently healthy control tissue samples of the bladder. DNA sequencing was used to confirm the identity of amplified fragments. Results: For all examined samples, survivin was the predominant transcript, being present in 83% of tumor and 25% of non-tumor bladder tissue samples, and survivin-2B was the least detected isoform. The expression levels of survivin and survivin-ΔEx3 was significantly higher in neoplastic compared to non-neoplastic tissues ( P < 0.001) and both the sensitivity and specificity of survivin were superior to survivin-ΔEx3 (83% and 75% for survivin and 76% and 64% for survivin-ΔEx3, respectively). Also, the expression levels of survivin and survivin-ΔEx3 showed a significant correlation ( P = 0.02) with tumor invasiveness (pT1/pTa). Conclusion: Our data revealed for the first time a differential expression pattern of survivin splice variants in bladder tissues, which potentially could have a practical usefulness in diagnosis and/or therapy of the tumor.

Survivin: Potential role in diagnosis, prognosis and targeted therapy of gastric cancer

Survivin is a protein that is highly expressed in a vast number of malignancies, but is minimally expressed in normal tissues. It plays a role as an inhibitor of cell death in cancer cells, thus facilitating the growth of these cells. In the case of gastric cancer, survivin is over-expressed in tumor cells and plays a role in the carcinogenesis process. Several studies on gastric cancer have indicated that there is a relationship between survivin expression and the ultimate behavior of the carcinoma. Since the expression pattern of survivin is selective to cancer cells, it has been described as an "ideal target" for cancer therapy. Currently, several pre-clinical and clinical trials are on-going to investigate the effects of interfering with survivin function in cancer cells as a biologic therapy. Survivin is a potentially significant protein in the diagnosis, prognosis and treatment of gastric tumors.

Expression of survivin and clinical correlation in patients with breast cancer

Survivin is a member of the inhibitor of apoptosis (IAP) family, which is also involved in the regulation of cell division and is also overexpressed and associated with parameters of poor prognosis in most human cancers, including carcinomas of the lung, breast, colon, stomach, esophagus and pancreas. This study examined the expression patterns of survivin in normal breast tissue, atypical hyperplasia, primary breast cancer and lymph node tissues involved in breast cancer and determined whether the expression of survivin is associated with the characteristics and prognosis of breast cancer. Formalin-fixed paraffin-embedded samples from 80 breast cancer, 20 atypical hyperplasia and 20 malignant lymph node tissue cases were immunostained using polyclonal survivin (Novus Biologicals, CO, USA). The degree of immunostaining was recorded on a scale of 0–3 according to the percentages of staining and distributions within the cytoplasm and nucleus. Survivin was expressed in 52, 14 and 17 of the 80 breast cancer (65%), atypical hyperplasia (70%) and breast cancer lymphoid (85%) specimens, respectively. Among those expressing cancer, 11.3%, 31.3% and 22.5% demonstrated only nuclear staining, only cytoplasmic staining and both nuclear and cytoplasmic staining, respectively. A statistical analysis revealed that cytoplasmic survivin expression was correlated with the stage, histological grade and L/N metastasis. In a Cox proportional hazard model analysis, the expression of survivin was not identified as a significant independent predictor of overall survival ( P = 0.168), although the decrease in the survival rate of survivin-positive patients did reach statistical significance ( P = 0.048). Conclusion: our results show that survivin is frequently overexpressed in primary breast cancer and its expression gradually increased from normal breast tissue to malignant lymph nodes. The expression of cytoplasmic survivin was common in breast cancer and could be both a useful diagnostic marker and an important source of prognostic information.

Evaluation of Survivin Reverse Transcriptase-Polymerase Chain Reaction for Noninvasive Detection of Bladder Cancer

Survivin, a member of the inhibitor of apoptosis gene family, is expressed in most common cancers. We investigated the expression pattern of survivin in the tumors of patients with bladder cancer and assessed the diagnostic potential of RT-PCR detection of survivin mRNA in urine. RT-PCR was used to analyze mRNA expression of survivin in 161 cases of bladder cancer, including TCC in 97, SCC in 53 and adenocarcinoma in 11, and their matched nontumor tissues. Urine specimens (50 ml) were collected from 84 patients in whom bladder cancer was documented by transurethral resection or biopsy, 41 with nonbladder cancer urological diseases and 42 healthy volunteers. Total RNA was extracted from urine sediments and RT-PCR was performed for survivin. Survivin expression was detected in all bladder cancer tissues. In contrast, survivin was not detectable in normal urothelium specimens. Urinary survivin was detected in urine samples from 51 of 53 patients with TCC, 22 of 25 with SCC and 6 of 6 with adenocarcinoma. Overall sensitivity was 94%. Survivin mRNA was not detected in any healthy volunteers. Positive results were obtained in 2 patients with renal cell carcinoma, 1 with hematuria and 1 with a contracted bladder but in none with other urological diseases. Overall specificity was 95%. Survivin mRNA detection in urine sediment using RT-PCR shows high sensitivity and specificity for bladder cancer. It may prove useful for the routine screening and monitoring of patients.

In vivo expression of survivin and its splice variant survivin‐2B: Impact on clinical outcome in acute myeloid leukemia

Survivin, a member of the inhibitor of apoptosis protein family, is expressed in most human cancers, but undetectable in normal differentiated adult tissue in vivo. Because of this cancer-related expression, survivin is a promising target for cancer therapy. To determine the expression and prognostic role of survivin in acute myeloid leukemia (AML), we investigated the mRNA expression pattern of survivin and of the splice variants survivin-2B and survivin-DeltaEx3 in adult (n = 74) and children (n = 31) with de novo AML using RT-PCR. Survivin was the predominant transcript variant in AML cells, whereas significantly lower levels of survivin-2B and survivin-DeltaEx3 were observed (p < or = 0.0001). Neither expression of survivin nor of any splice variant correlated with maturation stage (FAB subtypes, immunophenotype) or cytogenetic risk groups. For AML cases treated according to AMLCG92 (adult) and AML-BFM93 (children) protocols, respectively, expression patterns were correlated with clinical data: in adult AML (n = 51), low expression of survivin-2B correlated with a better overall survival (p = 0.05; mean survival time 19 months vs. 9 months) and a better eventfree survival (p < or = 0.01; 27 months vs. 10 months). In childhood AML (n = 31), high survivin-DeltaEx3 expression was associated with a shorter overall survival (p < or = 0.05; 24 months vs. 43 months). We conclude that certain survivin splice variants have potential prognostic impact for long-term therapy outcome in adult as well as childhood de novo AML.