<scp>FADD</scp> expression is associated with regional and distant metastasis in squamous cell carcinoma of the head and neck

Pattje, Wouter J.; Melchers, Lieuwe J.; Slagter‐Menkema, Lorian; Mastik, Mirjam F.; Schrijvers, Michiel L; Gibcus, Johan H.; Kluin, Philippus; Hoegen-Chouvalova, O; Laan, van der Bernard; Roodenburg, Jan; Wal, Jacqueline E. van der; Schuuring, Ed; Langendijk, Johannes A.

doi:10.1111/his.12174

Cited by 40 publications

(49 citation statements)

References 31 publications

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“…Amplification of chromosomal region 11q13, observed in four of the six cell lines, is a frequent event in sinonasal SCC35 as it is in head and neck SCC3738 and other tumors39. Apart from reports on the prognostic significance of this alteration373839, recent studies have indicated a role for amplification of CTTN and overexpression of cortactin (coded by CTTN ) in the progression from premalignant lesions to invasive carcinoma40. The gene CTTN lies just downstream of the smallest region of overlap of the four cell lines, however, three of the four amplifications include CTTN (SCCNC2, 6 and 7).…”

Section: Discussionmentioning

confidence: 90%

“…Focal aberrations are important because usually they concern very few genes and may indicate aberrant cellular pathways that could be useful targets for new anticancer drugs36. Amplification of chromosomal region 11q13, observed in four of the six cell lines, is a frequent event in sinonasal SCC35 as it is in head and neck SCC3738 and other tumors39. Apart from reports on the prognostic significance of this alteration373839, recent studies have indicated a role for amplification of CTTN and overexpression of cortactin (coded by CTTN ) in the progression from premalignant lesions to invasive carcinoma40.…”

Section: Discussionmentioning

confidence: 99%

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Establishment and genetic characterization of six unique tumor cell lines as preclinical models for sinonasal squamous cell carcinoma

García‐Inclán

López-Hernández

Alonso-Guervós

et al. 2014

Sci Rep

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Sinonasal squamous cell carcinomas (SCC) are rare tumors, etiologically related to occupational exposure to wood and leather dust. In spite of surgical and radiotherapeutic advances, the 5 year survival is still 30–50%. Therefore, alternative treatment options are needed. We report the establishment and characterization of six unique human sinonasal SCC cell lines, named SCCNC1, 2, 4, 5, 6 and 7. In vitro growth and invasion characteristics were evaluated and genetic profiles were compared to those of the original primary tumors. The population doubling times ranged from 21 to 34 hours. Cell lines SCCNC2 and 7 were highly invasive in matrigel. Five cell lines carried a high number of copy number alterations, including amplifications and homozygous deletions, while one showed only three abnormalities. Sequence analysis revealed three cell lines with TP53 mutation and none with KRAS or BRAF. Overexpression of p53 was observed in five, and of EGFR in four cell lines. None of the cell lines showed strong immunopositivity of p16 or presence of human papilloma virus. In conclusion, we have created six new cell lines that are clinically and genetically representative of sinonasal SCC and that will be a useful tool for the preclinical testing of new therapeutic agents.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Establishment and genetic characterization of six unique tumor cell lines as preclinical models for sinonasal squamous cell carcinoma

García‐Inclán

López-Hernández

Alonso-Guervós

et al. 2014

Sci Rep

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“…According to the previous reports, high expression of FADD was associated with factors indicating poor prognosis in squamous cell carcinoma of the head and neck [14,27] and oral squamous cell carcinoma [28]. However, contradictory clinical associations of FADD expression were also reported.…”

Section: Discussionmentioning

confidence: 99%

“…Cases showing a brown color in more than 50% of tumor cells were considered to be a strongly positive group. Cases showing light brown color in more than 5% and dark brown color in less than 50% of tumor cells were counted as a weakly positive group [14,20]. …”

Section: Methodsmentioning

confidence: 99%

“…FADD is an adaptor molecule interacting with many kinds of death receptors and induces apoptosis by caspase-8 [12,13]. FADD expression was associated with metastasis in squamous cell carcinoma of the head and neck [14] and poor prognosis in oral squamous cell carcinoma [15] and lung adenocarcinoma [16]. Because the amplification of FADD does not confined in a single gene, TMEM16A or PPFIA1 , which are in close proximity to FADD , may be amplified concomitantly.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic significance of TMEM16A, PPFIA1, and FADD expression in invasive ductal carcinoma of the breast

et al. 2014

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Background11q13 region is a frequently amplified locus in human malignancies. Among the genes located in this region, FADD is one of the alleged driving genes. Because amplification is not generally confined to a single gene and amplified genes may not show increased expression, we need to evaluate clinical significance of changes occurring in 11q13 region to understand their roles in carcinogenesis. Therefore, we screened expressions of FADD and closely located genes (PPFIA1 and TMEM16A) and evaluated the expressions to find clinical significance in invasive ductal carcinoma of the breast.MethodsNinety-eight cases of invasive ductal carcinoma of the breast were collected. Using archival tissues resected from the cases, we built a tissue microarray and used it in immunohistochemistry. We evaluated the association of FADD, PPFIA1, and TMEM16A expression scores with clinicopathological parameters, including disease-free survival.ResultsFADD expression was associated with T stage (P = 0.046). The combined score of FADD, PPFIA1, and TMEM16A gene expressions was associated with perineural invasion (P = 0.022). Although individual gene expressions of TMEM16A, FADD, and PPFIA1 failed to show significant association with disease-free survival, combined gene expression scores did show association with disease-free survival (P = 0.034).ConclusionsFADD, TMEM16A, and PPFIA1 gene expressions as a whole were associated with disease-free survival in breast cancer.

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Copy number gain of 11q13.3 genes associates with pathological stage in hypopharyngeal squamous cell carcinoma

Pattle¹,

Utjesanovic²,

Togo

et al. 2016

Genes Chromosomes & Cancer

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Squamous cell carcinomas of the hypopharynx (HPSCC) and oropharynx (OPSCC) have markedly different patient outcomes. Differences in HPV prevalence between these two patient groups may account for some of this difference, but other molecular markers of prognosis or pathological phenotype have not been established. Copy number gain of oncogenes is a well-established molecular change contributing to HNSCC development. Quantitative PCR was used to explore copy number gains of specific genes (3q -PIK3CA, TP63; 11q13.3 -CCND1, ANO1) in tumour DNA recovered from HPSCC (n=48) and OPSCC (n=52) patients. Associations between copy number gain, patient demographics, HPV/p16INK4a status and pathological stage were examined.HPV/p16 prevalence in HPSCC and OPSCC groups was 2.1% and 46.0% respectively. HPSCCs had frequent gains of CCND1 (56.3%) and ANO1 (56.3%) but few gains of PIK3CA (6.3%). By contrast, OPSCCs had significantly fewer CCND1 (23.1%) and ANO1 (17.3%) gains, and significantly more PIK3CA (26.9%) gains. A mutually exclusive relationship between HPV/p16 and 11q13.3 gains was observed in OPSCCs, while PIK3CA and TP63 gains were similar across HPVassociated and smoking/alcohol-associated patients. ANO1 gain was significantly linked to tumour pathology in HPSCC, associating with nodal metastasis and smaller and less invasive tumours at presentation (p=0.010). Our results provide a convincing link between a specific molecular change and disease phenotype that appears unique to our HPSCC population, supporting a model of 11q13.3 in promoting metastatic disease progression in HNSCC, and suggest a role for ANO1 as a molecular marker of metastatic disease. words

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FADD expression is associated with regional and distant metastasis in squamous cell carcinoma of the head and neck

Cited by 40 publications

References 31 publications

Establishment and genetic characterization of six unique tumor cell lines as preclinical models for sinonasal squamous cell carcinoma

Establishment and genetic characterization of six unique tumor cell lines as preclinical models for sinonasal squamous cell carcinoma

Prognostic significance of TMEM16A, PPFIA1, and FADD expression in invasive ductal carcinoma of the breast

Copy number gain of 11q13.3 genes associates with pathological stage in hypopharyngeal squamous cell carcinoma

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