The impact of microscopic versus macroscopic extranodal extension in oral cavity squamous cell carcinoma: National cancer database analysis and review of the literature

Quinton, Brooke A; Cabrera, Claudia I.; Tamaki, Akina; Li, Shawn; Fowler, Nicole; Rezaee, Rod; Teknos, Theodore; Pan, Quintin; Thuener, Jason

doi:10.1016/j.amjoto.2022.103511

Cited by 8 publications

(12 citation statements)

References 14 publications

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“…[12] The harmful effects of OSCC are primarily manifested in the destruction of oral structures and functions, invasion, and metastasis to the lymphatic system and other organs, leading to a decreased survival rate, especially when metastasis occurs in the cervical lymph nodes. [13,14] In-depth exploration of the molecular mechanisms of OSCC is crucial for targeted drug research. The main findings of this study indicate that the genes CDK1 and CCNA2 are highly expressed in OSCC, and higher expression of CDK1 and CCNA2 is associated with a poorer prognosis.…”

Section: Discussionmentioning

confidence: 99%

CDK1 and CCNA2 play important roles in oral squamous cell carcinoma

Zhang,

Di,

Zhang

et al. 2024

Medicine

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Oral squamous cell carcinoma (OSCC) is a malignant tumor that occurs in oral cavity and is dominated by squamous cells. The relationship between CDK1, CCNA2, and OSCC is still unclear. The OSCC datasets GSE74530 and GSE85195 configuration files were downloaded from the Gene Expression Omnibus (GEO) database and were derived from platforms GPL570 and GPL6480. Differentially expressed genes (DEGs) were screened. The weighted gene co-expression network analysis, functional enrichment analysis, gene set enrichment analysis, construction and analysis of protein–protein interaction (PPI) network, Comparative Toxicogenomics Database analysis were performed. Gene expression heatmap was drawn. TargetScan was used to screen miRNAs that regulate central DEGs. A total of 1756 DEGs were identified. According to Gene Ontology (GO) analysis, they were predominantly enriched in processes related to organic acid catabolic metabolism, centromeric, and chromosomal region condensation, and oxidoreductase activity. In Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the DEGs were mainly concentrated in metabolic pathways, P53 signaling pathway, and PPAR signaling pathway. Weighted gene co-expression network analysis was performed with a soft-thresholding power set at 9, leading to the identification of 6 core genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1). The gene expression heatmap revealed that core genes (CDK1, CCNA2) were highly expressed in OSCC samples. Comparative Toxicogenomics Database analysis demonstrated associations between the 6 genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1) and oral tumors, precancerous lesions, inflammation, immune system disorders, and tongue tumors. The associated miRNAs for CDK1 gene were hsa-miR-203a-3p.2, while for CCNA2 gene, they were hsa-miR-6766-3p, hsa-miR-4782-3p, and hsa-miR-219a-5p. CDK1 and CCNA2 are highly expressed in OSCC. The higher the expression of CDK1 and CCNA2, the worse the prognosis.

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Section: Discussionmentioning

confidence: 99%

CDK1 and CCNA2 play important roles in oral squamous cell carcinoma

Zhang,

Di,

Zhang

et al. 2024

Medicine

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“…Since ENE was first defined by Bennett et al, many studies have highlighted the association between ENE‐positivity and poor survival 17 . Large retrospective database studies of SCC of the oral cavity, oropharynx, and other head and neck primary sites document the survival detriment associated with ENE‐positivity 18,19 . The 8th edition of the AJCC Cancer Staging Manual has therefore incorporated evidence of ENE in the N classification of HNSCC 20 .…”

Section: Discussionmentioning

confidence: 99%

“…Until recently, there was little consensus among pathologists regarding the histologic definition of ENE across head and neck primary sites 17,18,22 . However, the 8th edition of the AJCC Cancer Staging Manual and the College of American Pathologist have created standardized criteria allowing for comparable studies between microscopic (≤2 mm from the capsule) and macroscopic ENE (>2 mm from the capsule) 18,19 .…”

Section: Discussionmentioning

confidence: 99%

Extranodal extension in laryngeal squamous cell carcinoma

Patel,

Vedula,

Shaari

et al. 2024

Laryngoscope Investig Oto

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ObjectiveAlthough large retrospective database studies have associated extranodal extension (ENE) with worse survival in several head and neck cancers, the prognostic significance of ENE in laryngeal squamous cell carcinoma (LSCC) remains unclear. Our study examines ENE and overall survival (OS) in LSCC.MethodsThe 2006–2017 National Cancer Database was queried for patients with LSCC undergoing surgical resection and neck dissection, with or without adjuvant therapy. Kaplan–Meier and multivariable Cox regression survival analyses were implemented to identify the independent impacts of pathologic nodal (pN) classification and ENE on OS.ResultsOf 4208 patients satisfying inclusion criteria, 2343 (55.7%) were pN0/ENE‐negative, 1059 (25.2%) were pN1‐2/ENE‐negative, and 806 (19.2%) were pN1‐2/ENE‐positive. The 5‐year OS of pN0/ENE‐negative, pN1‐2/ENE‐negative, and pN1‐2/ENE‐positive patients was 62.8%, 56.7%, and 32.9%, respectively (p < .001). Among pN1‐2/ENE‐positive patients undergoing no adjuvant therapy, adjuvant radiotherapy alone, and adjuvant chemoradiotherapy, 5‐year OS was 24.1%, 30.7%, and 36.7%, respectively (p < .001). After adjusting for patient demographics, clinicopathologic features, and adjuvant therapy, ENE‐positivity was associated with worse OS than ENE‐negativity (adjusted hazard ratio [aHR] 1.76, 95% confidence interval [CI] 1.53–2.02, p < .001). pN1/ENE‐positivity (aHR 1.82, 95% CI 1.31–2.54) and pN2/ENE‐positivity (aHR 1.89, 95% CI 1.49–2.40) were associated with worse OS than pN1/ENE‐negativity (p < .001). Microscopic (aHR 1.83, 95% CI 1.54–2.18) and macroscopic ENE‐positivity (aHR 1.75, 95% 1.35–2.26) were associated with worse OS than ENE‐negativity (p < .001).ConclusionENE‐positivity has prognostic significance in LSCC and is associated with worse OS than ENE‐negativity. pN classification did not have prognostic significance independent of ENE. ENE should be carefully considered when determining the prognosis of LSCC and selecting adjuvant therapy.Level of Evidence4.

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“…Concerns have been expressed in oral cavity cancer patients and the extent of ENE to be associated with differing prognosis and survival [50 ▪▪ ,90,91]. In a series of 384 patients with oral cavity cancer, it has been demonstrated that adjuvant chemoradiotherapy improves outcome in patients with ENEma, but the benefit in ENEmi was unclear, and authors concluded that future trials should focus on intensification of treatment for ENEma and alternative adjuvant strategies for patients with ENEmi [90].…”

Section: Therapeutic Implications Of Extranodal Extensionmentioning

confidence: 99%

“…Another series of 384 patients with oral cavity cancer showed that adjuvant chemoradiotherapy improves outcome in patients with ENEma, but the benefit in ENEmi was unclear [50 ▪▪ ]. A systematic review challenges [91] that the addition of chemotherapy to adjuvant radiotherapy may not provide a significant survival benefit in oral cavity patients with ENEmi and ENEma and recommends that further studies require a randomized controlled trial.…”

Section: Therapeutic Implications Of Extranodal Extensionmentioning

confidence: 99%

Extranodal extension in head and neck squamous cell carcinoma: need for accurate pretherapeutic staging to select optimum treatment and minimize toxicity

Bradley

2023

Current Opinion in Otolaryngology &Amp; Head &Amp; Neck Surgery

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Purpose of review In 2017, the American Joint Committee on Cancer (AJCC) introduced the inclusion of extracapsular nodal extension (ENE) into the N staging of nonviral head and neck squamous cell carcinoma (HNSCC), while retaining the traditional N classification based on the number and sizes of metastatic nodes. The extent of ENE was further defined as microscopic ENE (ENEmi) and major ENE (ENEma) based on extent of disease beyond the nodal capsule (≤ or > 2 mm). This article reviews the evidence and progress made since these changes were introduced. Recent findings The ‘gold standard’ for evaluation ENE is histopathologic examination, the current preferred primary treatment of patients with HNSCC is by radiation-based therapy ± chemotherapy or biotherapy. The current pretreatment staging is by imaging, which needs improved reliability of radiologic rENE assessment with reporting needs to consider both sensitivity and specificity (currently computed tomography images have high-specificity but low-sensitivity). Adjuvant chemotherapy is indicated for patients with ENEma to enhance disease control, whereas for patients with ENEmi, there is a need to assess the benefit of adjuvant chemotherapy. Evidence that the presence of pENE in HPV-positive oropharyngeal carcinoma is an independent prognostic factor and should be considered for inclusion in future AJCC editions has recently emerged. Summary There remains a paucity of data on the reliability of imaging in the staging of rENE, more so the for the accurate assessment of ENEmi. Optimistic early results from use of artificial intelligence/deep learning demonstrate progress and may pave the way for better capabilities in tumor staging, treatment outcome prediction, resulting in improved survival outcomes.

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The impact of microscopic versus macroscopic extranodal extension in oral cavity squamous cell carcinoma: National cancer database analysis and review of the literature

Cited by 8 publications

References 14 publications

CDK1 and CCNA2 play important roles in oral squamous cell carcinoma

CDK1 and CCNA2 play important roles in oral squamous cell carcinoma

Extranodal extension in laryngeal squamous cell carcinoma

Extranodal extension in head and neck squamous cell carcinoma: need for accurate pretherapeutic staging to select optimum treatment and minimize toxicity

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