Characterization of antigen processing machinery and Survivin expression in tonsillar squamous cell carcinoma

Weinman, Eric C.; Roche, Patrick C.; Kasperbauer, Jan L.; Steve, S.; Sargent, Daniel J.; Cheville, John C.; Murphy, Marina; Chen, Lieping; Wettstein, Peter J.; Gostout, Bobbie S.; Ferrone, Soldano; Strome, Scott E.

doi:10.1002/cncr.11311

Cited by 29 publications

(21 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently, several clinical trials targeting survivin with various approaches ranging from immunotherapy to antagonists are under way and might be broadly applicable to different tumours (Altieri, 2006). High levels of cytoplasmic survivin expression have been reported previously in OSCC (Weinman et al, 2003) with similar staining patterns as shown in our study in which 58% of all tumours prominently expressed survivin in the cytoplasm. Here, we found a significantly inverse correlation between cytoplasmic survivin expression and HPV-associated carcinomas.…”

Section: Discussionsupporting

confidence: 88%

Nuclear survivin expression is associated with HPV-independent carcinogenesis and is an indicator of poor prognosis in oropharyngeal cancer

et al. 2008

View full text Add to dashboard Cite

The relationship between expression of the inhibitor of apoptosis protein survivin and the presence of high-risk human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OSCC) remains unclear. This also accounts for its role as a predictor of survival. Therefore, we conducted a multicentre retrospective study on 106 consecutive oropharyngeal cancer patients. Human papillomavirus sequences were detected by nested PCR protocols. Survivin and p16 expression as a surrogate marker for HPV status were analysed by immunohistochemistry. Sequences of high-risk HPV were detected in 29% of cases. Prominent cytoplasmatic expression of survivin was found in 58% of cases and nuclear expression of survivin was found in 19% of the survivin-positive tumours. Nuclear expression of survivin was significantly correlated with HPV-negative tumours (P ¼ 0.023) and with a poor diseasefree survival rate with an estimated 3-year disease-free survival probability of 35% for tumours with nuclear expression of survivin vs 78% for tumours with non-nuclear expression of survivin (hazard ratio ¼ 8.264; 95% confidence interval (95% CI) ¼ 2.510 -27.210; Po0.001). In multivariate analysis, p16 expression status as well as nuclear expression of survivin were strong independent and opposing prognostic indicators of disease-free survival (hazard ratio ¼ 0.068; 95% CI ¼ 0.005 -0.892; P ¼ 0.041 and hazard ratio ¼ 15.975; 95% CI ¼ 2.377 -107.360; P ¼ 0.004, respectively). Our data show that nuclear accumulation of survivin correlates with HPV-independent carcinogenesis and is an independent predictor of poor survival in patients with OSCC.

show abstract

Section: Discussionsupporting

confidence: 88%

Nuclear survivin expression is associated with HPV-independent carcinogenesis and is an indicator of poor prognosis in oropharyngeal cancer

et al. 2008

View full text Add to dashboard Cite

show abstract

“…In a recent paper about survivin, 37% of TC was highly expressed and was associated with tumor progression. 35 However, the present study revealed a higher frequency (71.2%) of survivin expression and that the overexpression of survivin was not significant by any parameters.…”

Section: Discussioncontrasting

confidence: 79%

HPV integration begins in the tonsillar crypt and leads to the alteration of p16, EGFR and c‐myc during tumor formation

Kim

Koo

Kang

et al. 2007

Intl Journal of Cancer

196

175

View full text Add to dashboard Cite

The prevalence of human papillomavirus (HPV) infection is high in the oropharyngeal mucosal regions, of which the tonsil is the most commonly affected. There may be a link between HPV and the pathogenesis of tonsillar cancer (TC), because of common anatomical characteristics between cervical and tonsillar cancer. We aimed to clarify whether HPV directly affects the oncogenesis and biologic behavior of TC by making a comparison between infection prevalence, physical status and viral loading numbers, and clinicopathologic prognostic factors. To compare HPV-related molecules between TC and tonsillitis (CFT), p16, survivin, HIF-1a, skp-1, cyclin A, cyclin B1, c-myc and EGFR were investigated. We observed a significant difference in HPV prevalence between 52 TCs and 69 CFTs (73.1% vs. 11.6%), and most of the HPVs were type 16 (87.2%) and nonepisomal (94.1%). Most TCs associated with HPV arose from the tonsillar crypts, and tended to be inverted and poorly differentiated. Compared with HPV-negative TC, HPV-positive TC showed a strong association with p16 overexpression (p < 0.0001), and an inverse association with EGFR amplification (p 5 0.0478). HPV-16 integration status was strongly associated with c-myc amplification (p 5 0.034) and HIF-1a overexpression (p 5 0.022). HPV-16 integration could be directly related to tonsillar carcinogenesis initially in tonsillar crypts, followed by cell cycle aberration such as p16 overexpression related to the G1-S phase. ' 2006 Wiley-Liss, Inc.Key words: human papillomavirus; integration; tonsil cancer; p16; epidermal growth factor receptor Human papillomavirus (HPV) may be postulated to play a role in the pathogenesis of palatine tonsillar cancer (TC), not only due to its morphological similarities to cervical cancer but also because the mucosal squamous epithelium, similar to that of the uterine cervix, is easily exposed to viral infection. HPV infection is prevalent in the oropharyngeal mucosal regions, and the tonsil is the most commonly affected anatomical region in the oropharynx.1,2 Furthermore, TC frequently has a verrucous or papillomatous appearance, with tumor cells showing features of HPV infection, namely koilocytotic atypia. However, it remains uncertain whether HPV is directly associated with the malignant transformation of oropharngeal tumors.The molecular biology of viral oncogenesis has been well established. The viral protein E6 promotes the degradation of p53 and E7 inactivates pRb, usually followed by viral integration into the host genome.3,4 For viral integration, disruption occurs most frequently in an E2 open reading frame (ORF), the E1 ORF being disrupted in a minor proportion of patients. Both are important in viral replication and transcription. More specifically, the breakage of E2 allows for the dysregulation of the E6/E7 oncoprotein, which eventually leads to malignant transformation. 5 In the non-integrated episomal state, the transcriptional level of E6/E7 is regulated by a promoter in the long control region in high-risk HPV-infected cells. It is ...

show abstract

“…Lastly, the frequency of tapasin down-regulation in laryngeal SCC lesions is markedly higher than that in maxillary sinus SCC (11) and tonsillar carcinoma lesions (38), and is markedly lower than that in colorectal carcinoma (35) and renal cell carcinoma (36) lesions. Whether the differences we have indicated reflect differences in the extent of genetic instability and selective pressure on tumor cell populations in various types of malignancies, in the clinical characteristics of the patients investigated, in the histopathologic characteristics of the lesions analyzed, and/or in the sensitivity of the immunohistochemical technique used remains to be determined.…”

Section: Discussionmentioning

confidence: 93%

HLA Class I Antigen Down-regulation in Primary Laryngeal Squamous Cell Carcinoma Lesions as a Poor Prognostic Marker

Ogino¹,

Shigyo²,

Ishii³

et al. 2006

Cancer Research

Self Cite

164

124

View full text Add to dashboard Cite

We have investigated the role of antigen-processing machinery (APM) component defects in HLA class I antigen downregulation in laryngeal squamous cell carcinoma (SCC) lesions and assessed the clinical significance of these defects. To this end, 63 formalin-fixed, paraffin-embedded tumor lesions were examined for APM component and HLA class I antigen expression by immunohistochemistry. Calnexin, calreticulin, and ERp57 were down-regulated in f25% of the lesions tested, whereas LMP2, TAP1, tapasin, and HLA class I antigens were down-regulated in at least 70% of the lesions tested. LMP2 and tapasin expression was significantly correlated with HLA class I antigen expression suggesting APM component defects as a mechanism underlying HLA class I antigen downregulation in laryngeal SCC lesions. The expression of most APM components and HLA class I antigens was correlated with the extent of CD8 + T cell infiltration into tumor lesions. Furthermore, LMP2 and HLA class I antigen down-regulation and low CD8 + T cell infiltration were significantly associated with reduced patients' survival. Multivariate analysis identified HLA class I antigen down-regulation as an independent unfavorable prognostic marker. This association is likely to reflect the reduction in the extent of CD8 + T cell infiltration in laryngeal SCC lesions. (Cancer Res 2006; 66(18): 9281-9)

show abstract

Characterization of antigen processing machinery and Survivin expression in tonsillar squamous cell carcinoma

Cited by 29 publications

References 22 publications

Nuclear survivin expression is associated with HPV-independent carcinogenesis and is an indicator of poor prognosis in oropharyngeal cancer

Nuclear survivin expression is associated with HPV-independent carcinogenesis and is an indicator of poor prognosis in oropharyngeal cancer

HPV integration begins in the tonsillar crypt and leads to the alteration of p16, EGFR and c‐myc during tumor formation

HLA Class I Antigen Down-regulation in Primary Laryngeal Squamous Cell Carcinoma Lesions as a Poor Prognostic Marker

Contact Info

Product

Resources

About