Microsatellite alteration in head and neck squamous cell carcinoma patients from a betel quid-prevalent region

Lin, Jin‐Ching; Wang, Chen‐Chi; Jiang, Rong–San; Wang, Wenyi; Liu, Shih–An

doi:10.1038/srep22614

Cited by 12 publications

(17 citation statements)

References 25 publications

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“…However, individuals who both consumed alcohol and chewed betel quid experienced a stepwise increase in the cumulative risk of larynx SCC . In patients with head and neck SCC in Taiwan (a betel quid–prevalent region), microsatellite instability in the tumor‐free surgical margins was associated with LR . These findings may support our observation that betel quid chewing increased the risk of disease relapse.…”

Section: Discussionsupporting

confidence: 77%

Low expression of pRB predicts disease relapse in early glottic cancer treated with transoral laser microsurgery

Lee¹,

Fang²,

Li³

et al. 2018

The Laryngoscope

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Objectives/Hypothesis To elucidate the associations among the immunohistochemical expression of tumor markers, clinicopathological variables, and disease‐free survival (DFS) in patients with early‐stage glottic squamous cell carcinoma (SCC) who underwent transoral laser microsurgery (TLM) as the primary treatment. Study Design Retrospective chart review. Methods The records of consecutive patients with Tis‒T2N0 glottic SCC who underwent TLM between August 1, 2012 and October 31, 2015 were reviewed. Expression of Bcl‐2, pRB, p16INK4A, p53, c‐Myc, E‐cadherin, and EGFR was examined using tissue microarrays containing tumor specimens through immunohistochemistry. Three‐year DFS rates were calculated. Results A total of 65 consecutive patients were identified, of which 28 were excluded due to insufficient tissue (n = 22) and low biomarker quality (n = 6). Therefore, 37 patients with complete records were included. The included patients were significantly older and had a more advanced type of cordectomy than did the excluded patients (P = .015 and .009, respectively). According to the findings of univariate analysis, age, betel quid chewing, type of cordectomy, BCL‐2 expression, and pRB expression significantly predicted 3‐year DFS. According to the findings of multivariate analysis, age (adjusted hazard ratio: 0.94, 95% CI: 0.88‐1.00), betel quid chewing (adjusted hazard ratio: 5.07, 95% CI: 1.32‐19.44), and pRB expression (adjusted hazard ratio: 0.02, 95% CI: 0.00‐0.28) were independent predictors of 3‐year DFS. Conclusions Low pRB expression is a potential biomarker for predicting disease relapse after primary TLM for early‐stage glottic SCC and may help to identify high‐risk patients who can subsequently undergo intensive management. Level of Evidence 4 Laryngoscope, 129:E220–E226, 2019

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Section: Discussionsupporting

confidence: 77%

Low expression of pRB predicts disease relapse in early glottic cancer treated with transoral laser microsurgery

Lee¹,

Fang²,

Li³

et al. 2018

The Laryngoscope

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“…It has been estimated that MSI is present in ∼40% of patients with HNSCC (106). The frequency of MSI in an endemic betelquid chewing region is about the same as the otherwise nonendemic regions, having a rate of 37.9% (107). Despite the fact that these TMB-high cancers are more immunogenic, unlike those immunogenic-desert tumors, half of the TMB-high patients still do not respond to anti-PD-1 immunotherapy (108).…”

Section: Prediction Of Response To Anti-pd-1 Immunotherapy In Hnsccmentioning

confidence: 99%

Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer

Kok

2020

Front. Oncol.

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Starting in 2014, large phase III clinical trials began to disclose the study results of using programmed death (PD)-1 immune checkpoint inhibitors (ICIs) (pembrolizumab, nivolumab) and PD-ligand (L)1 (atezolizumab, durvalumab, avelumab) ICIs immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). In the recurrent and metastatic (R/M), cisplatin-refractory setting, nivolumab achieved a 2.2-fold increase of the median 1-year overall survival as compared with investigators' choice of salvage chemotherapy (36.0 vs. 16.6%). A paradigm shift to the winning regimen, pembrolizumab combined with platinum and infusional fluorouracil, has outperformed the past gold standard of cetuximab-based platinum and fluorouracil combination in terms of overall survival (median, 13.6 vs. 10.1 mo) when administered as the first-line treatment for R/M HNSCC. Nevertheless, many patients still did not respond to the PD-1/PD-L1 checkpoint inhibitor treatment, indicating innate, adapted, or quickly acquired resistance to the immunotherapy. The mechanisms of resistance to ICIs targeting the PD-1/PD-L1 signaling pathway in the context of HNSCC are the focus of this review. The past 5 years have seen improved understanding of the mechanisms underlying checkpoint inhibition resistance in tumor cells, such as: tumor cell adaption with malfunction of the antigen-presenting machinery via class I human leukocyte antigen (HLA), reintroduction of cyclin D-cyclin-dependent kinase (CDK) 4 complex to cell cycles, enrichment of CD44+ cancer stem-like cells, or development of inactivating mutation in IKZF1 gene; impairment of T-cell functions and proliferation through mutations in the interferon-γ-regulating genes, suppression of the stimulator of interferon genes (STING) pathway, or resulted from constitutional nutritional iron deficiency state; metabolic reprogramming by cancer cells with changes in metabolites such as GTP cyclohydrolase 1, tetrahydrobiopterin, kynurenine, indoleamine 2,3-dioxygenase, and arginase 1; defective dendritic cells, CD-69 sufficient state; and the upregulation or activation of the alternative immune checkpoints, including lymphocyte activation gene-3 (LAG3), T-cell Kok Immune Evasion From PD-1/PD-L1 Immunotherapy immunoglobulin and ITIM domain (TIGIT)/CD155 pathway, T-cell immunoglobulin mucin-3 (TIM-3), and V domain-containing Ig suppressor of T-cell activation (VISTA). Several potential biomarkers or biosignatures, which could predict the response or resistance to the PD-1/PD-L1 checkpoint immunotherapy, are also discussed.

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“…MSI has been reported to be correlated with dysfunction of the mismatch repair (MMR) system, which repairs DNA replication errors. Dysfunction of the MMR system may lead to carcinogenesis owing to accumulative mutations in pivotal genes. In Taiwan, OCSCC has been closely correlated with the use of betel quid, which is classified by the International Agency for Research on Cancer as a group 1 human carcinogen.…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of surgical margins in oral cavity cancer

Liu

Wang²,

Jiang

et al. 2018

British Journal of Surgery

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Background: A histological, tumour-free surgical margin does not guarantee recurrence-free survival in patients with cancer. This study investigated the association between microsatellite alteration in tumour-free surgical margins and local recurrence in patients with oral cavity squamous cell carcinoma.Methods: Patients with histologically confirmed oral cavity squamous cell carcinoma were enrolled in this prospective study. Cancerous specimens, corresponding surgical margins and peripheral blood were obtained. Microsatellite alteration was investigated using six dinucleotide microsatellite markers. All samples were amplified by PCR, followed by automatic fragment analysis.Results: Microsatellite alteration was identified in 100 specimens (69⋅0 per cent) from 145 patients. Among them, 85 specimens carried loss of heterozygosity, whereas 55 had microsatellite instability (MSI). Patients with MSI at the surgical margin had a higher risk of local recurrence on multivariable analysis (odds ratio 7⋅17, 95 per cent c.i. 3⋅49 to 14⋅73).

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Microsatellite alteration in head and neck squamous cell carcinoma patients from a betel quid-prevalent region

Cited by 12 publications

References 25 publications

Low expression of pRB predicts disease relapse in early glottic cancer treated with transoral laser microsurgery

Low expression of pRB predicts disease relapse in early glottic cancer treated with transoral laser microsurgery

Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer

Genetic analysis of surgical margins in oral cavity cancer

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