Prognostic significance of tumor budding, tumor‐stroma ratio, cell nests size, and stroma type in laryngeal and pharyngeal squamous cell carcinomas

Abstract

Background Despite immune microenvironment of head and neck squamous cell carcinoma (HNSCC) has been studied, there are no sufficient data on the role of tumor stroma factors. The aim of the study was to explore the prognostic and predictive role of these factors in a large series of HNSCC. Methods This is a retrospective study of 266 patients with laryngeal and pharyngeal SCC. Clinical data were correlated with the following histological parameters: tumor‐stroma ratio (TSR), tumor budding activity (BA), cell nests size (CNS), and stroma type. Results Stroma‐rich tumors, tumor budding, smaller CNS at core and front area, and fibroblastic stroma type, were all adverse prognostic factors (P < 0.0001, 0.001, 0.003, 0.001, 0.007, respectively). Stroma‐poor tumors and with larger CNS showed good response to induction chemotherapy (P = 0.009 and 0.02, respectively). Conclusions TSR, tumor budding, CNS, and stroma type are important prognostic and predictive factors in laryngeal and pharyngeal SCC.

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

“…2,8,9,11,12,20,27,34,40,45,48,54 This definition is in accordance with the recent recommendation by the International Tumor Budding Consensus Conference (ITBCC 2016) in colorectal cancer, 55 and also agrees with studies on other cancers. 2,8,9,11,12,20,27,34,40,45,48,54 This definition is in accordance with the recent recommendation by the International Tumor Budding Consensus Conference (ITBCC 2016) in colorectal cancer, 55 and also agrees with studies on other cancers.…”

“…Of note, our recent systematic search found 16 studies on tumor budding in OSCC and the meta-analysis confirmed the significance of tumor budding in prognostication of lymph node metastasis and survival. Similar results on the significance of tumor budding were reported in an independent cohort of hypopharyngeal SCC by Imai et al, 11 and also for pharyngeal SCC by Karpathiou et al 34 Specifically, identification of high intensity of tumor budding in HNSCC has been associated with metastasis to cervical lymph nodes. 33 In laryngeal cancer, Sarioglu et al 8 were the first to evaluate tumor budding in HNSCC and they reported the prognostic power of tumor budding to predict distant metastasis in laryngeal carcinoma.…”

“…Therefore, this recently accumulated evidence indicates that tumor budding is an important factor, that can identify patients with high-risk for nodal metastasis and who should thus be considered to receive elective neck dissection. 8,9,11,34,35 Further, for WPOI such evidence in these subsites has not been widely shown in the recent research. In addition, a recent systematic review showed that tumor budding was also a valuable marker of tumor aggressiveness that can be evaluated in technically satisfactory diagnostic biopsies, and not only in surgically resected specimens.…”

“…28 Further, the findings in these reports have been based on large patient cohorts. [34][35][36] In hypopharyngeal cancer, Boxberg et al 35 reported a significant prognostic value for tumor budding in an analysis of patient cohort of laryngeal and hypopharyngeal subsites. 10 Subsequently, after that meta-analysis many studies have been published indicating that tumor budding is a promising prognostic marker in OSCC, 21,[29][30][31][32] including the recent meta-analysis with tumors from various subsites of the head and neck.…”

“…33 In laryngeal cancer, Sarioglu et al 8 were the first to evaluate tumor budding in HNSCC and they reported the prognostic power of tumor budding to predict distant metastasis in laryngeal carcinoma. 34 Interestingly, the association between tumor budding and nodal metastasis is not limited to mucosal HNSCC only as a recent study reported the importance of tumor budding in prediction of nodal metastasis in cutaneous HNSCC. [34][35][36] In hypopharyngeal cancer, Boxberg et al 35 reported a significant prognostic value for tumor budding in an analysis of patient cohort of laryngeal and hypopharyngeal subsites.…”