Expression of the antiapoptosis gene, Survivin, predicts death from recurrent colorectal carcinoma

Sarela, Abeezar; Macadam, Robert; Farmery, Susan M.; Markham, Alex F.; Guillou, P. J.

doi:10.1136/gut.46.5.645

Cited by 297 publications

(201 citation statements)

References 21 publications

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“…In this study, we demonstrated that survivin was not detected in the gastric mucosa from normal control subjects whereas the adjacent non-tumour gastric mucosa of survivin-positive tumours occasionally expressed survivin. This finding is in keeping with those found in colorectal and oesophageal cancer where survivin expression was demonstrated in adjacent normal tissues (Sarela et al, 2000;Kato et al, 2001). Past epidemiological studies revealed that first-degree relatives have an approximately three-fold increase in risk of developing gastric carcinoma, suggesting the existence of a genetic susceptibility to cancer (Zanghieri et al, 1990;La Vecchia et al, 1992).…”

Section: Discussionsupporting

confidence: 88%

Increased expression of survivin in gastric cancer patients and in first degree relatives

Leung

Ebert

et al. 2002

Br J Cancer

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Survivin was recently described as an apoptosis inhibitor. Its pathogenic role in gastric cancer is largely unknown. Expression of survivin in gastric cancer and non-cancer first-degree relatives, and its association with apoptosis and cyclo-oxygenase-2 expression was investigated. Fifty gastric cancer, 30 non-cancer first-degree relatives, 20 normal controls and five gastric cancer cell lines were studied. Survivin and cyclo-oxygenase-2 were evaluated by reverse transcriptase-polymerase chain reaction, immunohistochemistry and Western blot. Survivin expression was absent from normal gastric mucosa. All five cancer cell lines and 34 out of 50 (68%) human gastric cancer tissues expressed survivin mRNA. Survivin expression was less frequent (22%; P50.001) in adjacent non-tumour gastric tissues. Immunohistochemistry and Western blot obtained similar findings. Gastric cancers with survivin expression displayed significantly reduced apoptosis (P=0.02), and associated with cyclo-oxygenase-2 overexpression at both mRNA (P=0.001) and protein levels (P=0.041). Moreover, survivin mRNA was detected in the gastric mucosa of eight (27%) non-cancer relatives. Expression in non-cancer patients showed positive correlation with H. pylori infection (P=0.004). This demonstrates the frequent expression of survivin in gastric cancer and in first-degree relatives. Coexpression of survivin and cyclo-oxygenase-2 may suggest multiple pathways contributing to the inhibition of apoptosis in gastric cancer.

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Section: Discussionsupporting

confidence: 88%

Increased expression of survivin in gastric cancer patients and in first degree relatives

Leung

Ebert

et al. 2002

Br J Cancer

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“…This is in agreement with previously reported links between high levels of survivin expression and worse prognosis of the neoplastic lesions along with better prognosis in HPV-positive OSCC. 57 In retrospective trials, survivin expression has been correlated with reduced overall survival in several solid tumors, [58][59][60][61][62][63] especially in OSCC; 27,64,65 similarly, HPV infection could influence oral carcinogenesis, consistently with results suggesting that HPV-positive patients have significantly reduced overall and disease-specific mortality. 22,66 Besides Gillison et al, 57 Herrero et al 34 suggested HPV-positive OSCC as a distinct small subgroup of tumors with different biomolecular and clinical behaviors.…”

Section: Discussionmentioning

confidence: 96%

Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: Use of fuzzy neural networks

Muzio

D’Angelo

Procaccini

et al. 2005

Intl Journal of Cancer

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Our aim was to evaluate in oral squamous cell carcinoma (OSCC) the relationship between some cell cycle markers and HPV infection, conditionally to age, gender and certain habits of patients, and to assess the ability of fuzzy neural networks (FNNs) in building up an adequate predictive model based on logic inference rules. Eighteen cases of OSCC were examined by immunohistochemistry for MIB-1, PCNA and survivin expression; presence of HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR (nPCR, MY09-MY11/GP5-GP6), and HPV genotype was determined by direct DNA sequencing. Data were analyzed by traditional statistics (TS) and FNNs. HPV DNA was found in 9/18 OSCCs (50.0 %) without any significant higher risk of HPV infection with respect to the sociodemographic variables considered ( p > 0.2), apart from tobacco smoking, reported in 44.4% of OSCC HPV-positive vs. 100% HPV-negative subjects ( p = 0.029). Regarding cell cycle markers, TS and FNN revealed that survivin was expressed significantly more in HPV-negative than in HPVpositive OSCC [root mean-square error (RMSE) = 5.89 3 10 -6 , % predicted 100.0]; furthermore, smoking played a protective role for survivin expression in HPV-positive cases (OR = 0.019, 95%CI 0.001-0.723, RMSE = 0.20, % of prevision 94.4). FNN, although on a small sample size, allowed us to confirm data by TS and to hypothesize a different cell cycle pattern for HPV-positive vs. HPV-negative OSCC. In the latter cases, the relevance of apoptotic vs. proliferative markers suggested that they may be related to the different supposed outcome of HPV-negative OSCC and that HPV may have a protective role in the expression level of survivin, especially in tobacco smokers. ' 2005 Wiley-Liss, Inc.Key words: human papillomavirus; survivin; oral squamous cell carcinoma; fuzzy neural network; carcinogenesis OSCC is rapidly increasing in incidence and represents the most frequent malignant oral tumor. The incidence of metastasis depends on the degree of cellular differentiation, deep invasion and site of the primary tumor; however, outcome is difficult to predict if only standard clinicopathologic parameters are taken into account. Biologic markers that can help to identify lesions with an aggressive phenotype and worse prognosis need to be identified.Since the majority of human neoplasms are characterized by an imbalance of the regulatory cell cycle control processes, the study of OSCC using the expression of proteins involved in the critical checkpoints of cell apoptosis and growth starts by elucidating the processes of carcinogenesis and appears to have good prognostic value. 1 Indeed, we know that apoptosis, or programmed cell death, and its suppression are involved in the carcinogenesis of several tumors; this process, mediated by caspases and cysteine proteinases present as proenzymes, is inhibited by several proteins, such as those of the Bcl-2 and IAP families. Survivin is an IAP protein, which is abundantly expressed in most solid and hematologic malignancies but undetectable in ...

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“…Interference with survivin function induces pleiotropic celldivision defects and apoptosis (Li et al, 1999), suggesting a potential role at the interface between cell division and apoptosis control. In retrospective trials, survivin expression correlated with unfavourable neuroblastoma (Adida et al, 1998a), reduced overall survival in primitive colorectal (Kawasaki et al, 1998) and recurrent colorectal cancer (Sarela et al, 2000), non-small-cell lung cancer (Monzo et al, 1999), breast cancer (Tanaka et al, 2000), and increased rates of recurrences in bladder cancer (Swana et al, 1999). Consistent with a critical role of apoptosis inhibition in tumour progression, overexpression of survivin in model cancer cell types provided a broad cytoprotective mechanism, counteracting apoptosis induced by FAS/TNF legation, proapoptotic Bax, effector caspases, and various chemotherapeutic drugs (Tamm et al, 1998).…”

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confidence: 99%

Survivin expression in oral squamous cell carcinoma

et al. 2003

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A series of 110 cases of oral squamous cell carcinoma (SCC) together with six lymph node and one distant metastatic lesions was analysed for expression of survivin, a recent apoptosis inhibitor, by immunohistochemistry and Western blotting. In total, 91 cases (82.7%) of carcinoma and all metastasis (seven cases, 100%) were positive for survivin expression, with weighted survivin scores ranging from 1 to 4. In contrast, normal oral epithelium did not express survivin. There was no significant correlation between survivin expression and age, sex, tumour size, the presence of lymph node and distant metastases. Survivin expression was increased in poorly differentiated tumours, even if differences were not statistically significant. In contrast, when analysed for prognostic significance, patients with low survivin expression had statistically significant better survival rates than the group with high survivin expression (Po0.05). These data suggest that survivin expression may identify cases of oral SCC with more aggressive and invasive phenotype.

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Expression of the antiapoptosis gene, Survivin, predicts death from recurrent colorectal carcinoma

Abstract: (Gut 2000;46:645-650)

Cited by 297 publications

References 21 publications

Increased expression of survivin in gastric cancer patients and in first degree relatives

Increased expression of survivin in gastric cancer patients and in first degree relatives

Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: Use of fuzzy neural networks

Survivin expression in oral squamous cell carcinoma

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