PTEN as prognostic and predictive marker in postoperative radiotherapy for squamous cell cancer of the head and neck.

Śnietura, Mirosław; Jaworska, Magdalena; Młynarczyk-Liszka, Joanna; Pigłowski, Wojciech; Woźniak, Grzegorz; Lange, Dariusz; Suwiński, Rafał

doi:10.1200/jco.2010.28.15_suppl.5519

Cited by 13 publications

(19 citation statements)

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“…The conflicting results of previous studies may be explained by the different methods (such as different antibody, different detection system, scoring method, and cut‐off value) used to examine the immunohistochemical PTEN expression. Low expression of PTEN by immunohistochemistry in HNSCC has been reported with frequencies of 30%–60% . Further studies are needed to confirm our findings and to better understand the relationship between miR‐21 and PTEN expression in HNSCC.…”

Section: Discussionsupporting

confidence: 56%

“…Low expression of PTEN by immunohistochemistry in HNSCC has been reported with frequencies of 30%-60%. [35][36][37] Further studies are needed to confirm our findings and to better understand the relationship between miR-21 and PTEN expression in HNSCC. Chang et al performed a study in colorectal cancer using qRT-PCR and showed that PDCD4 mRNA levels were reduced significantly when miR-21 was upregulated; however, there were no differences in cPDCD4 protein between tumor and normal tissues.…”

Section: Discussionmentioning

confidence: 69%

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Human papillomavirus‐stratified analysis of the prognostic role of miR‐21 in oral cavity and oropharyngeal squamous cell carcinoma

Won

Sun

et al. 2014

Pathology International

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Human papillomavirus (HPV) infection plays a significant role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Expression of miR-21 has a prognostic role in a wide variety of cancers. The upregulation of miR-21 suppresses a number of target genes, including phosphatase tensin homologue (PTEN) and programmed cell death 4 (PDCD4). We investigated the association between the expression of miR-21 and the clinical features of HNSCC using stratified analysis based on HPV infection status. HPV status and miR-21 expression in HNSCC tissues from 167 patients were evaluated using in situ hybridization. The expression of PDCD4 and PTEN was examined by immunohistochemistry. The up-regulation of stromal miR-21 expression occurred in 40.6% of HPV-negative samples and 28.3% of the HPV-positive group. In HPV-stratified multivariate analysis, high miR-21 expression was associated with poor cancer-specific survival in HPV-negative tumors, but not in HPV-positive tumors. There was a significant association between miR-21 and cytoplasmic PDCD4 overexpression in HPV-negative HNSCCs. We suggest that stromal miR-21 expression is an independent prognostic factor in HPV-negative tumors and miR-21 may play different roles depending on HPV infection status.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 69%

Human papillomavirus‐stratified analysis of the prognostic role of miR‐21 in oral cavity and oropharyngeal squamous cell carcinoma

Won

Sun

et al. 2014

Pathology International

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“…Loss-of-function mutations in PTEN gene have been associated with disease progression and resistance to radiotherapy in head and neck and pulmonary squamous cell carcinoma. 21,22 A validated loss-offunction mutation in PTEN, Q17*, was observed in only a single patient. We noted three functionally significant mutations in FBXW7 including W446* and W486* in two patients, leading to premature truncation of the WD2 repeat domain.…”

Section: Overview Of Somatic Mutationsmentioning

confidence: 99%

Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma

Zilberg

Lee

et al. 2018

Modern Pathology

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Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequencing of 48 clinically relevant genes was performed on DNA extracted from formalin-fixed and paraffin-embedded high-risk primary head and neck cutaneous squamous cell carcinomas that remained non-metastatic at minimum follow-up of 24 months. Associations of somatic mutations with clinicopathologic characteristics were evaluated and compared with those described in the literature for metastatic disease. Alterations in 44 cancer-associated genes were identified. TP53 was mutated in 100% of cases; APC, ATM, ERBB4, GNAQ, KIT, RB1 and ABL1 were altered in 60% of cases. FGFR2 mutations (40%) were exclusively seen in patients with perineural invasion. MLH1 mutations were exclusively seen in the two younger patients (<45 years). Lower incidences of NOTCH1 mutations were observed compared with that described in metastatic head and neck cutaneous squamous cell carcinoma in the literature. Somatic mutations susceptible to EGFR inhibitors, and other small molecular targeted therapeutics were seen in 60% of cases. This study provides insights into somatic mutations in non-metastatic, high-risk head and neck cutaneous squamous cell carcinoma and identifies potential therapeutic targets. Alterations in FGFR2 and NOTCH1 may have roles in local and distant disease progression.

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“…Although this may be because of the limited number of loci examined, there is some evidence to suggest that maintenance or overexpression of PTEN portends worse prognosis in HNSCC because of increased radioresistance. 19 Although controversial, 20 if true, this may mean that in our highrisk cohorts, inactivating mutations in PTEN were selected against.…”

Section: Mutational Landscape In High-risk Head and Neck Squamous Celmentioning

confidence: 99%

Mutation frequency in 15 common cancer genes in high‐risk head and neck squamous cell carcinoma

et al. 2014

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Background With prior studies having looked at unselected cohorts, we sought to explore the mutational landscape in a high-risk group of head and neck squamous cell carcinoma (HNSCC) tumors. Methods A multiplexed polymerase chain reaction (PCR) assay evaluating 68 loci in 15 genes was performed on 64 patients with high-risk HNSCC. Because of the frequent PIK3CA and AKT1 mutations in patients with oropharyngeal carcinoma, we evaluated the relationship between mutation status and both clinical/pathologic variables and tumor control in this subgroup. Results Seventeen of 64 patients harbored mutations in the assayed loci: 16% in PIK3CA, 9% in TP53, 2% in AKT1, and 2% in epidermal growth factor receptor (EGFR). The frequency of PIK3CA/AKT1 mutations in oropharyngeal and sinonasal primaries was increased compared to other primary sites (35% vs 6%; p = .005). There was no relationship between mutation status and overall survival (OS), disease-specific death, or progression in the oropharyngeal cohort. Conclusion We identified frequent PIK3CA mutations in patients with high-risk HNSCC confined predominantly to the oropharyngeal and sinonasal subsites; for the first time, mutation in AKT1 has been identified in HNSCC.

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PTEN as prognostic and predictive marker in postoperative radiotherapy for squamous cell cancer of the head and neck.

Cited by 13 publications

References 0 publications

Human papillomavirus‐stratified analysis of the prognostic role of miR‐21 in oral cavity and oropharyngeal squamous cell carcinoma

Human papillomavirus‐stratified analysis of the prognostic role of miR‐21 in oral cavity and oropharyngeal squamous cell carcinoma

Analysis of clinically relevant somatic mutations in high-risk head and neck cutaneous squamous cell carcinoma

Mutation frequency in 15 common cancer genes in high‐risk head and neck squamous cell carcinoma

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