Survivin expression in oral squamous cell carcinoma

Muzio, Lorenzo Lo; Pannone, Giuseppe; Staibano, Stefania; Mignogna, Michele Davide; Rubini, Corrado; Mariggiò, Maria A.; Procaccini, Maurizio; Ferrari, Francesca; Rosa, Gaetano De; Altieri, Dario C.

doi:10.1038/sj.bjc.6601402

Cited by 134 publications

(140 citation statements)

References 24 publications

(21 reference statements)

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“…Some reports have revealed reduced expression of both cadherins and catenins in certain tumours, for example, oral squamous cell carcinoma. 34 In the current study, there appeared to be no correlation between reduced expression of E-cadherin and b-catenin.…”

Section: B-catenin Expression In Paget's Disease Of the Breastcontrasting

confidence: 66%

Reduced E-cadherin expression correlates with disease progression in Paget's disease of the vulva but not Paget's disease of the breast

et al. 2008

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Section: B-catenin Expression In Paget's Disease Of the Breastcontrasting

confidence: 66%

Reduced E-cadherin expression correlates with disease progression in Paget's disease of the vulva but not Paget's disease of the breast

et al. 2008

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“…37 In addition, high expression levels of inhibitors of apoptosis, such as BclX L and survivin, have been reported in head-and-neck squamous cell carcinomas. [38][39][40][41] Expression of pRb was detected in 81% of the tumors. Approximately half of all tumors showed strong nuclear expression in the tumor cells, with expression levels equal to or higher than the adjacent normal squamous epithelium, whereas pRb downregulation was observed in the remaining cases.…”

Section: Discussionmentioning

confidence: 99%

P21Cip1/WAF1 expression is strongly associated with HPV-positive tonsillar carcinoma and a favorable prognosis

et al. 2009

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Human papillomavirus is involved in the carcinogenesis of tonsillar squamous cell carcinomas. Here, we investigated the expression and the prognostic value of key cell cycle proteins in the pRb and p53 pathways in both human papillomavirus type 16-positive and -negative tonsillar squamous cell carcinomas. Using immunohistochemistry, 77 tonsillar squamous cell carcinomas with known human papillomavirus type 16 status and clinical outcome were analyzed for expression of Ki67, p16 INK4A, cyclin D1, pRb, p14 ARF , MDM2, p53, p21 Cip1/WAF1 , and p27 KIP1 . Results were correlated with each other and with clinical and demographic patient data. A total of 35% of tonsillar carcinomas harbored integrated human papillomavirus type 16 DNA and p16 INK4A overexpression, both being considered essential features for human papillomavirus association. These tumors also showed the overexpression of p14 ARF (Po0.0001) and p21 Cip1/WAF1 (P ¼ 0.001), and downregulation of pRb (Po0.0001) and cyclin D1 (P ¼ 0.027) compared with the human papillomavirus-negative cases. Univariate Cox regression analyses revealed a favorable survival rate for non-smokers (P ¼ 0.006), as well as for patients with T1-2 tumors (Po0.0001) or tumors showing low expression of cyclin D1 (P ¼ 0.028), presence of human papillomavirus and overexpression of p16 INK4A (P ¼ 0.01), p14 ARF (P ¼ 0.02) or p21 Cip1/WAF1 (P ¼ 0.004). In multivariate regression analyses, smoking and tumor size, as well as expression of cyclin D1 and p21 Cip1/WAF1 , were found to be independent prognostic markers. We conclude that human papillomavirus positivity in tonsillar squamous cell carcinomas strongly correlates with p21 Cip1/WAF1 and p14 ARF overexpression and downregulation of pRb and cyclin D1. In particular p21 Cip1/WAF1 overexpression is an excellent favorable prognosticator in tonsillar squamous cell carcinomas. Modern Pathology ( Head-and-neck squamous cell carcinoma is the sixth most prevalent malignancy in the world, contributing 6% of new cancer cases annually worldwide. 1,2 These tumors have a 5-year survival rate of approximately 50%, which has not improved in the last two decades. 3 Well-recognized risk factors in the etiology of head-and-neck squamous cell carcinomas are extensive tobacco and alcohol consumption in B90% of cases, as well as oncogenic human papillomaviruses (HPVs), predominantly HPV type 16. 3,4 Interestingly, the association of HPV is strongest for tonsillar squamous cell carcinoma with a prevalence up to 50%. [5][6][7][8]

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“…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%

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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Survivin expression in oral squamous cell carcinoma

Cited by 134 publications

References 24 publications

Reduced E-cadherin expression correlates with disease progression in Paget's disease of the vulva but not Paget's disease of the breast

Reduced E-cadherin expression correlates with disease progression in Paget's disease of the vulva but not Paget's disease of the breast

P21Cip1/WAF1 expression is strongly associated with HPV-positive tonsillar carcinoma and a favorable prognosis

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

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