Hallmarks of cancer: Tumor budding as a sign of invasion and metastasis in head and neck cancer

Mäkitie, Antti; Almangush, Alhadi; Rodrigo, Juan P.; Ferlito, Alfio; Leivo, Ilmo

doi:10.1002/hed.25872

Cited by 51 publications

(39 citation statements)

References 66 publications

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“…Of note, both patterns take into consideration the degree of keratinocyte dyscohesion in the advancing invasive front of tumor (presence of tumor clusters composed of ≤15 tumor cells) ( 32 , 69 ). Tumor budding, defined as the presence of isolated single cells or small tumor islands composed of less than five cells in the stroma of the invasive tumor ( 70 ), corresponds to the most noncohesive pattern of invasion. In fact, studies have shown that tumor budding is composed of cells exhibiting typical features of epithelial mesenchymal transition, with increasing invasiveness ( 71 ).…”

Section: Discussionmentioning

confidence: 99%

The Impact of Histopathological Features on the Prognosis of Oral Squamous Cell Carcinoma: A Comprehensive Review and Meta-Analysis

et al. 2021

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ObjectiveOver many decades, studies on histopathological features have not only presented high-level evidence of contribution for treatment directions and prognosis of oral squamous cell carcinoma (OSCC) but also provided inconsistencies, making clinical application difficult. The 8th TNM staging system of OSCC has acknowledged the importance of some histopathological features, by incorporating depth of invasion (DOI) to T category and extranodal extension (ENE) to N category. The aim of this systematic review with meta-analysis is to determine the most clinically relevant histopathological features for risk assessment and treatment planning of OSCC and to elucidate gaps in the literature.MethodsA systematic review was conducted using PRISMA guidelines, and the eligibility criteria were based on population, exposure, comparison, outcome, and study type (PECOS). PubMed, Cochrane, Scopus, and Web of Science were searched for articles exploring the impact of histopathological features on OSCC outcomes with Cox multivariate analysis. Pooled data were subjected to an inverse variance method with random effects or fixed effect model, and the risk of bias was evaluated using quality in prognosis studies (QUIPS). Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.ResultsThe study included 172 articles published from 1999 to 2021. Meta-analyses confirmed the prognostic potential of DOI, ENE, perineural invasion, lymphovascular invasion, and involvement of the surgical margins and brought promising results for the association of bone invasion, tumor thickness, and pattern of invasion with increased risk for poor survival. Although with a small number of studies, the results also revealed a clinical significance of tumor budding and tumor-stroma ratio on predicted survival of patients with OSCC. Most of the studies were considered with low or moderate risk of bias, and the certainty in evidence varied from very low to high.ConclusionOur results confirm the potential prognostic usefulness of many histopathological features and highlight the promising results of others; however, further studies are advised to apply consistent designs, filling in the literature gaps to the pertinence of histopathological markers for OSCC prognosis.Systematic Review RegistrationInternational Prospective Register of Systematic Reviews (PROSPERO), identifier CRD42020219630.

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Section: Discussionmentioning

confidence: 99%

The Impact of Histopathological Features on the Prognosis of Oral Squamous Cell Carcinoma: A Comprehensive Review and Meta-Analysis

et al. 2021

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“…Obviously, the few factors analyzed in this review (T classification and laryngeal subsite) are clearly insufficient to accurately predict the risk of lymph node metastasis. Other tumor features also have been reported to be relevant in the development of lymph node metastases, such as the infiltrating pattern of growth of the tumor, "tumor budding" and lymphovascular and perineural invasion [69][70][71][72]; molecular changes, such as loss of N33, STK11 and TP53 [73]; as well as immune alteration, such as HLA-E overexpression [74]. However, the means to assess these characteristics are not readily available in all institutions.…”

Section: Discussionmentioning

confidence: 99%

Incidence of Occult Lymph Node Metastasis in Primary Larynx Squamous Cell Carcinoma, by Subsite, T Classification and Neck Level: A Systematic Review

Sanábria

Shah

Medina

et al. 2020

Cancers

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Background: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on the subsite of the primary tumor, T classification and neck node levels involved. Methods: All studies included provided the rate of occult metastases in cN0 larynx squamous cell carcinoma patients. The main outcome was the incidence of occult metastasis. The pooled incidence was calculated with random effects analysis. Results: 36 studies with 3803 patients fulfilled the criteria. The incidence of lymph node metastases for supraglottic and glottic tumors was 19.9% (95% CI 16.4–23.4) and 8.0% (95% CI 2.7–13.3), respectively. The incidence of occult metastasis for level I, level IV and level V was 2.4% (95% CI 0–6.1%), 2.0% (95% CI 0.9–3.1) and 0.4% (95% CI 0–1.0%), respectively. For all tumors, the incidence for sublevel IIB was 0.5% (95% CI 0–1.3). Conclusions: The incidence of occult lymph node metastasis is higher in supraglottic and T3–4 tumors. Level I and V and sublevel IIB should not be routinely included in the elective neck treatment of cN0 laryngeal cancer and, in addition, level IV should not be routinely included in cases of supraglottic tumors.

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“…From a prognostic point of view, an advanced tumor stage, sphenoid sinus involvement, orbital, dural or brain infiltration and high-grade histology were established as prognostic factors of poor outcome [7,[11][12][13][14]. Recently, tumor budding (TB), a known risk factor in particular for colorectal carcinoma (CRC), but also certain head and neck cancer subtypes [13,[15][16][17][18][19][20], has been discussed as negative prognostic factor in ITAC [21]. This hypothesis is particularly interesting, since ITAC morphologically, immuno-phenotypically and in part molecularly show a substantial resemblance to CRC [22,23].…”

Section: Introductionmentioning

confidence: 99%

Reappraisal of Grading in Intestinal-Type Sinonasal Adenocarcinoma: Tumor Budding as an Independent Prognostic Parameter

Meerwein

Brada

Soyka

et al. 2022

Head and Neck Pathol

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Since sinonasal intestinal-type adenocarcinomas (ITAC) show resemblance to colorectal adenocarcinomas, we aimed to investigate novel prognostic factors of outcome, with particular focus on the role of tumor budding (TB). Retrospective clinico-pathological single-institution study on consecutive ITAC patients between 1996 and 2020. Histopathological parameters including conventional subtypes and TB features (low, intermediate, high) were evaluated with the aid of pancytokeratin (AE1/AE3) immunohistochemical staining. Parameters were correlated to clinical data and outcome. A total of 31 ITAC patients were included. Overall, 19/31 patients (61.3%) presented with stage III/IV disease. Presence of lymph node or distant metastases was rare (1/31 patient, 3.2%). Treatment protocols consisted of tumor resection in 30/31 patients (96.8%) and primary radiochemotherapy in 1/31 patient (3.2%). Adjuvant radiation therapy was conducted in 20/30 surgically treated patients (66.7%). The 3- and 5-year overall survival (OS) was 83.9% and 78.3% and the 3- and 5-years disease-specific survival (DSS) 83.7% % and 78.5%, respectively. The presence of intermediate/high TB (defined as ≥ 5 buds) was associated with both, worse DSS (log rank p = 0.03) and OS (log rank p = 0.006). No patient with low TB revealed progressive disease or died of the disease. No association between TB and tumor stage or conventional tumor subtype was found. Tumor budding seems to be an independent prognostic factor of worse outcome in ITAC.

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Hallmarks of cancer: Tumor budding as a sign of invasion and metastasis in head and neck cancer

Cited by 51 publications

References 66 publications

The Impact of Histopathological Features on the Prognosis of Oral Squamous Cell Carcinoma: A Comprehensive Review and Meta-Analysis

The Impact of Histopathological Features on the Prognosis of Oral Squamous Cell Carcinoma: A Comprehensive Review and Meta-Analysis

Incidence of Occult Lymph Node Metastasis in Primary Larynx Squamous Cell Carcinoma, by Subsite, T Classification and Neck Level: A Systematic Review

Reappraisal of Grading in Intestinal-Type Sinonasal Adenocarcinoma: Tumor Budding as an Independent Prognostic Parameter

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