Co-expression of fibroblast growth factor receptor 3 with mutant p53, and its association with worse outcome in oropharyngeal squamous cell carcinoma

Nannapaneni, Sreenivas; Griffith, Christopher C.; Magliocca, Kelly R.; Chen, Wanqi; Lyu, Xueying; Wang, Dongsheng; Wang, Xu; Shin, Dong M.; Chen, Zhuo G.; Saba, Nabil F.

doi:10.1371/journal.pone.0247498

Cited by 7 publications

(8 citation statements)

References 41 publications

(36 reference statements)

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“…Due to the relatively small number of patients analyzed, our results should be interpreted with caution. Nevertheless, mRNA levels of FGFR3 mRNA have been associated with worse DFS in oropharyngeal squamous cell carcinoma (p = 0.005) [33] and in non-muscleinvasive bladder cancer (HR 3.78, p < 0.001) [34]. The FGFR3 mRNA level is also a negative prognostic factor for lung adenocarcinoma [35] and squamous cell laryngeal cancer [36], where high FGFR3 expression was significantly correlated with shorter overall survival (OS).…”

Section: Discussionmentioning

confidence: 99%

FGFR1–4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer

Moes-Sosnowska¹,

Skupińska

Lechowicz³

et al. 2022

IJMS

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While fibroblast growth factor receptors (FGFRs) are involved in several biological pathways and FGFR inhibitors may be useful in the treatment of squamous non-small cell lung cancer (Sq-NSCLC), FGFR aberrations are not well characterized in Sq-NSCLC. We comprehensively evaluated FGFR expression, fusions, and variants in 40 fresh-frozen primary Sq-NSCLC (stage IA3–IV) samples and tumor-adjacent normal tissues using real-time PCR and next-generation sequencing (NGS). Protein expression of FGFR1–3 and amplification of FGFR1 were also analyzed. FGFR1 and FGFR4 median gene expression was significantly (p < 0.001) decreased in tumors compared with normal tissue. Increased FGFR3 expression enhanced the recurrence risk (hazard ratio 4.72, p = 0.029), while high FGFR4 expression was associated with lymph node metastasis (p = 0.036). Enhanced FGFR1 gene expression was correlated with FGFR1 protein overexpression (r = 0.75, p = 0.0003), but not with FGFR1 amplification. NGS revealed known pathogenic FGFR2,3 variants, an FGFR3::TACC3 fusion, and a novel TACC1::FGFR1 fusion together with FGFR1,2 variants of uncertain significance not previously reported in Sq-NSCLC. These findings expand our knowledge of the Sq-NSCLC molecular background and show that combining different methods increases the rate of FGFR aberrations detection, which may improve patient selection for FGFRi treatment.

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Section: Discussionmentioning

confidence: 99%

FGFR1–4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer

Moes-Sosnowska¹,

Skupińska

Lechowicz³

et al. 2022

IJMS

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“…A plethora of other markers, of which some have stem cell or tumor suppressor character, have also been studied by IHC for their possible predictive role in survival in HPV + TSCC, BOTSCC, and OPSCC, and here, only a few are described [ 33 , 34 , 42 , 104 ]. Early on, it was shown that having low CD44 intensity expression or CD98 expression was correlated with better survival irrespective of the HPV status in the tumors, while for tumor suppressor genes LRIG1-3 , only high LRIG1 expression was correlated with a better clinical outcome [ 33 , 34 , 42 ].…”

Section: The Search Of Prognostic or Targetable Biomarkers In Hpv + And Hpv − Tscc Botscc And Opsccmentioning

confidence: 99%

“…Using NGS in HNSCC, several different features have been disclosed between HPV + and HPV − cancers, including the potential of targeting some of them [ 28 , 43 , 49 , 67 , 105 , 106 , 107 , 108 , 109 ]. HPV + TSCC, BOTSCC, or OPSCC mainly presented mutations in the PIK3CA , notch homolog 1 translocation-associated (NOTCH1) , and FGFR3 genes, while HPV − tumors mainly had mutations in TP53 and cyclin-dependent kinase inhibitor 2A/B ( CDKN2A/B) [ 28 , 43 , 49 , 67 , 104 , 105 , 106 , 107 , 108 , 109 , 110 ]. The prognostic values of some of these genes have been reported, but there are discrepancies between the studies, and the data should be taken with caution.…”

Section: The Search For Prognostic or Targetable Biomarkers In Hpv + And Hpv − Tscc Botscc And Opscmentioning

confidence: 99%

Prognostic Markers and Driver Genes and Options for Targeted Therapy in Human-Papillomavirus-Positive Tonsillar and Base-of-Tongue Squamous Cell Carcinoma

Näsman

Holzhauser

Kostopoulou

et al. 2021

Viruses

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The incidence of Human-papillomavirus-positive (HPV+) tonsillar and base-of-tongue squamous cell carcinoma (TSCC and BOTSCC, respectively) is increasing epidemically, but they have better prognosis than equivalent HPV-negative (HPV−) cancers, with roughly 80% vs. 50% 3-year disease-free survival, respectively. The majority of HPV+ TSCC and BOTSCC patients therefore most likely do not require the intensified chemoradiotherapy given today to head and neck cancer patients and would with de-escalated therapy avoid several severe side effects. Moreover, for those with poor prognosis, survival has not improved, so better-tailored alternatives are urgently needed. In line with refined personalized medicine, recent studies have focused on identifying predictive markers and driver cancer genes useful for better stratifying patient treatment as well as for targeted therapy. This review presents some of these endeavors and briefly describes some recent experimental progress and some clinical trials with targeted therapy.

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“…Conversely, FGFR3 mutations in HPV positive OPSCC are linked with improved disease free survival ( BERSANI et al, 2018 ). A further study highlighted that FGPR3 mutations were predominantly identified in an HPV negative OPSCC cohort, and in combination with mutant TP53 was linked with a worse overall prognosis ( Nannapaneni et al, 2021 ). Thus, extrapolating this data, combined mutant TP53 and mutated FGFR3 in the HPV positive OPSCC cohort is linked to improved OS.…”

Section: Human Papilloma Virus Positive Oropharyngeal Squamous Cell Carcinoma Linked With Disease Progression/recurrencementioning

confidence: 99%

The Role of Human Papilloma Virus in Dictating Outcomes in Head and Neck Squamous Cell Carcinoma

Brennan

Baird

O’Regan

et al. 2021

Front. Mol. Biosci.

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The Human Papilloma Virus (HPV) is an oncogenic virus which is associated with the development of head and neck squamous cell carcinoma (HNSCC), predominantly within the oropharynx. Approximately 25% of oropharyngeal squamous cell carcinoma (OPSCC) cases worldwide are attributable to HPV infection, with an estimated 65% in the United States. Transmission is via exposure during sexual contact, with distinctive anatomical features of the tonsils providing this organ with a predilection for infection by HPV. No premalignant lesion is identifiable on clinical examination, thus no comparative histological features to denote the stages of carcinogenesis for HPV driven HNSCC are identifiable. This is in contrast to HPV-driven cervical carcinoma, making screening a challenge for the head and neck region. However, HPV proffers a favorable prognosis in the head and neck region, with better overall survival rates in contrast to its HPV negative counterparts. This has resulted in extensive research into de-intensifying therapies aiming to minimize the morbidity induced by standard concurrent chemo-radiotherapy without compromising efficacy. Despite the favorable prognosis, cases of recurrence and/or metastasis of HPV positive HNSCC do occur, and are linked with poor outcomes. HPV 16 is the most frequent genotype identified in HNSCC, yet there is limited research to date studying the impact of other HPV genotype with respect to overall survival. A similar situation pertains to genetic aberrations associated in those with HPV positive HNSCC who recur, with only four published studies to date. Somatic mutations in TSC2, BRIP1, NBN, TACC3, NFE2l2, STK11, HRAS, PIK3R1, TP63, and FAT1 have been identified in recurrent HPV positive OPSCC. Finding alternative therapeutic strategies for this young cohort may depend on upfront identification of HPV genotypes and mutations which are linked with worse outcomes, thus ensuring appropriate stratification of treatment regimens.

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Co-expression of fibroblast growth factor receptor 3 with mutant p53, and its association with worse outcome in oropharyngeal squamous cell carcinoma

Cited by 7 publications

References 41 publications

FGFR1–4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer

FGFR1–4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer

Prognostic Markers and Driver Genes and Options for Targeted Therapy in Human-Papillomavirus-Positive Tonsillar and Base-of-Tongue Squamous Cell Carcinoma

The Role of Human Papilloma Virus in Dictating Outcomes in Head and Neck Squamous Cell Carcinoma

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