Expression of the Apoptosis Inhibitor Survivin in Aggressive Squamous Cell Carcinoma

Muzio, Lorenzo Lo; Staibano, S.; Pannone, Giuseppe; Mignogna, Michele Davide; Mariggio, Ada; Salvatore, G; Chieffi, Paolo; Tramontano, Donatella; Rosa, Gaetano De; Altieri, Dario C.

doi:10.1006/exmp.2001.2367

Cited by 103 publications

(91 citation statements)

References 22 publications

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“…Normal oral mucosa specimens showed positivity only in sporadic cells of basal and parabasal layers and were considered negative for survivin expression by immunohistochemistry (score ¼ 0), in agreement with previous observations (Lo Muzio et al, 2001) Survivin expression in oral SCC Immunohistochemical staining for survivin was observed in 20 -100% of cancer cells. The immunostaining was prevalently cytoplasmic in poorly differentiated cases with sporadic prominent nuclear staining in well-differentiated areas, as already reported in cervical mucosa (Frost et al, 2002).…”

Section: Survivin Expression In Normal Oral Mucosasupporting

confidence: 89%

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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Section: Survivin Expression In Normal Oral Mucosasupporting

confidence: 89%

Survivin expression in oral squamous cell carcinoma

et al. 2003

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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: 97%

“…HPV-negative OSCC characterized by high levels of survivin expression could have a poor clinical response compared to HPVpositive OSCC characterized by lower levels of survivin expression since in retrospective trials survivin expression correlated with reduced overall survival in OSCC. 27,67 Conversely, survivin expression in HPV-positive OSCC may be useful to detect lesions with unfavorable behavior, similar to that of HPV-negative oral cancers, which almost always have high survivin expression. HPV-positive OSCC lesions with higher levels of survivin expression could have a worse clinical outcome: survivin could stop apoptosis and promote cell transformation.…”

Section: Discussionmentioning

confidence: 99%

“…27 Negative control slides without primary antibody were included for each staining. Survivin expression was quantified by the following scoring method: mean percentage of positive tumor cells was determined examining 300 cells in at least 5 areas at Â400 magnification and assigned to one of the following categories: 0, <5%; 1, 5-25%; 2, 26-50%; 3, >51%.…”

Section: Immunohistochemical Analysismentioning

confidence: 99%

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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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“…Lack of caspase 3 resulted in increased proliferation and decreased differentiation of embryonic keratinocytes 36. However, the possible involvement of this pathway in CSCC remains to be clarified, although increased expression of survivin, an apoptosis inhibitor targeting caspase 3 and caspase 7, was observed in CSCC tumors 37, 38, 39.…”

Section: Notch Signaling In Cutaneous Squamous Cell Carcinoma (Cscc)mentioning

confidence: 99%

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

et al. 2016

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The role of Notch pathway in tumorigenesis is highly variable. It can be tumor suppressive or pro‐oncogenic, typically depending on the cellular context. Squamous cell carcinoma (SCC) is a cancer of the squamous cell, which can occur in diverse human tissues. SCCs are one of the most frequent human malignancies for which the pathologic mechanisms remain elusive. Recent genomic analysis of diverse SCCs identified marked levels of mutations in NOTCH1, implicating Notch signaling pathways in the pathogenesis of SCCs. In this review, evidences highlighting NOTCH's role in different types of SCCs are summarized. Moreover, based on accumulating structural information of the NOTCH receptor, the functional consequences of NOTCH1 gene mutations identified from diverse SCCs are analyzed, emphasizing loss of function of Notch in these cancers. Finally, we discuss the convergent view on an intriguing possibility that Notch may function as tumor suppressor in SCCs across different tissues. These mechanistic insights into Notch signaling pathways will help to guide the research of SCCs and development of therapeutic strategies for these cancers.

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Expression of the Apoptosis Inhibitor Survivin in Aggressive Squamous Cell Carcinoma

Cited by 103 publications

References 22 publications

Survivin expression in oral squamous cell carcinoma

Survivin expression in oral squamous cell carcinoma

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

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

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