Molecular biology of squamous cell carcinoma of the head and neck

Perez-Ordoñez, Bayardo; Beauchemin, M.; Jordan, Richard C.

doi:10.1136/jcp.2003.007641

Cited by 261 publications

(213 citation statements)

References 93 publications

Supporting

Mentioning

196

Contrasting

Unclassified

Order By: Relevance

“…Study of the natural history of oral cancer and precancer should identify critical stages that can be used to develop preventive strategies or for early detection that may improve the survival rate associated with oral cancer. We attempted to study the role of FHIT in a multistep malignant transformation model of oral carcinogenesis (42). Our results showed that FHIT downregulation is an early frequent event in oral carcinogenesis and may provide a predictor marker for disease progression and outcome alongside other conventional clinicopathologic and molecular markers that are in use.…”

Section: Discussionmentioning

confidence: 99%

Fragile Histidine Triad Expression in Oral Squamous Cell Carcinoma and Precursor Lesions

Kujan

Oliver

Roz

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

Pupose: Fragile histidine triad (FHIT) expression in precursor oral lesions (POL) and oral squamous cell carcinomas (OSCC) was studied with regard to (a) the frequency of loss of FHIT expression, (b) whether loss of FHITexpression correlates with degree of dysplasia in POLs, (c) whether FHIT loss predicts high-risk POLs that are more likely to transform, and (d) whether FHIT loss in OSCCs correlates with survival. Experimental Design: Ninety-four POLs and 86 OSCCs were immunostained for FHIT. Survival analysis was done for cases with validated clinical outcomes. Results: By optimizing the immunostaining protocol, we found that FHIT is expressed in a distinctive strong nuclear and weak cytoplasmic pattern in oral tissues. Loss of FHIT expression was found in 42 of 94 (45%) POLs and in 66 of 86 (77%) OSCCs. We observed a statistically significant positive correlation between frequency of FHIT loss and increasing grade of dysplasia (m 2 = 13.8; degrees of freedom = 4; P = 0.008). Loss of FHITexpression in POLs that progressed to malignancy was more frequent than in those that did not [17 of 25 (68%) versus 12 of 29 (41.4%), respectively]. This difference was statistically significant (m 2 = 3.8; degrees of freedom = 1; P = 0.046). In OSCCs, loss of FHIT staining indicated a worse prognosis (survival rate, 36.2%) than when positive FHIT staining was observed (survival rate, 50%), but the difference was not statistically significant (P = 0.546, Kaplan-Meier, log-rank). Conclusions: FHITseems to localize to both nuclear and cytoplasmic domains. FHIT inactivation occurs early in oral carcinogenesis and may be useful molecular marker for progressive dysplastic oral lesions.

show abstract

Section: Discussionmentioning

confidence: 99%

Fragile Histidine Triad Expression in Oral Squamous Cell Carcinoma and Precursor Lesions

Kujan

Oliver

Roz

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…A number of studies have suggested that genetic variation modulates cancer risk associated with environmental risk factors and that genetic variation may serve as a biomarker to identify individuals at risk of developing cancer [2]. Cumulative genetic alterations have been shown to be associated with phenotypic progression of SCCHN, resulting in inactivation of multiple tumor suppressor genes and activation of proto-oncogenes [3]. Among them, p16INK4A at chromosome 9p and RASSF1A at chromosome 3p are two major tumor suppressor genes epigenetically inactivated at the early stage from normal mucosa to dysplasia [4,5].…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms of the DNMT3B gene and risk of squamous cell carcinoma of the head and neck: A case–control study

et al. 2008

View full text Add to dashboard Cite

DNA-methyltransferase-3B (DNMT3B) may play an oncogenic role during tumorigenesis, and its genetic variants have been reportedly to be associated with risk of several cancers, but few studies have investigated their roles in head and neck cancer. Here we report a hospital-based case-control study with 832 SCCHN patients and 843 cancer-free controls of non-Hispanic whites that evaluated the association between two DNMT3B single nucleotide polymorphisms (SNPs) DNMT3B-149C>T (rs2424913) and DNMT3B-579G>T (rs2424909) in the promoter region and risk of squamous cell carcinoma of the head and neck (SCCHN). We found that compared with C-allele carriers, the DNMT3B-149 TT genotype was statistically significantly associated with increased risk of SCCHN (adjusted OR, 1.35, 95% CI, 1.01-1.80, P = 0.043), whereas the DNMT3B-579 TT genotype showed only a non-statistically significant risk compared with G-allele carriers. Further analysis of the effects of combined genotypes suggested that subjects with either DNMT3B-149 TT or DNMT3B-579 TT homozygous genotypes had statistically significantly increased risk of SCCHN (adjusted OR = 1.36, 95% CI = 1.07-1.73, P = 0.013). Stratification analysis showed a more profound risk in the subgroups of the young (≤57 years, the median age of the controls), males, current smokers, current drinkers, and patients with primary tumor sites of pharynx and larynx. This large study provides reliable risk estimates for associations between DNMT3B variants and SCCHN risk in non-Hispanic whites, and our findings are consistent with that of previously reported cancer case-control studies of other cancers. Further mechanistic studies are needed to unravel the underlying molecular mechanisms.

show abstract

“…All of these treatment modalities have undergone improvements over the last several decades and have led to improvements in outcomes for some types of HNSCC (for example, advanced laryngeal and pharyngeal carcinoma; ref. 3). Despite these advances, the 5-year survival rate for HNSCC as a whole remains at ∼50% (2).…”

Section: Introductionmentioning

confidence: 99%

Cisplatin Treatment Induces a Transient Increase in Tumorigenic Potential Associated with High Interleukin-6 Expression in Head and Neck Squamous Cell Carcinoma

Poth

Guminski

Thomas

et al. 2010

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Head and neck squamous cell carcinoma (HNSCC) is characterized by the 5-year survival rate of ∼50%. Despite aggressive surgical, radiation, and chemotherapeutic interventions, 30% to 40% of patients die from the development of recurrent or disseminated disease that is resistant to chemotherapy. As a model of recurrence, we examined the effects of cisplatin on the ability of head and neck cancer cells to initiate tumors in a xenotransplant model. HNSCC cells were treated in vitro with cisplatin at a concentration that elicited >99% cytotoxicity and assessed for tumorigenic potential in nonobese diabetic/severe combined immunodeficient mice. HNSCC cells that survived cisplatin treatment formed tumors in nonobese diabetic/severe combined immunodeficient mice more efficiently than nontreated cells. Cisplatin-resistant cells were characterized using clonal analysis, in vivo imaging, and transcriptomic profiling. Preliminary functional assessment of a gene, interleukin-6 (IL-6), highly upregulated in cisplatin-treated cells was carried out using clonogenicity and tumorigenicity assays. We show that cisplatin-induced IL-6 expression can contribute to the increase in tumorigenic potential of head and neck cancer cells but does not contribute to cisplatin resistance. Finally, through clonal analysis, we show that cisplatin-induced IL-6 expression and cisplatin-induced tumorigenicity are stochastically derived. We report that cisplatin treatment of head and neck cancer cells results in a transient accumulation of cisplatin-resistant, small, and IL-6-positive cells that are highly tumorigenic. These data also suggest that therapies that reduce IL-6 action may reduce recurrence rates and/or increase disease-free survival times in head and neck cancer patients, and thus, IL-6 represents a promising new target in HNSCC treatment. Mol Cancer Ther; 9(8); 2430-9. ©2010 AACR.

show abstract

Molecular biology of squamous cell carcinoma of the head and neck

Cited by 261 publications

References 93 publications

Fragile Histidine Triad Expression in Oral Squamous Cell Carcinoma and Precursor Lesions

Fragile Histidine Triad Expression in Oral Squamous Cell Carcinoma and Precursor Lesions

Polymorphisms of the DNMT3B gene and risk of squamous cell carcinoma of the head and neck: A case–control study

Cisplatin Treatment Induces a Transient Increase in Tumorigenic Potential Associated with High Interleukin-6 Expression in Head and Neck Squamous Cell Carcinoma

Contact Info

Product

Resources

About