Evaluation of the Potential Prognostic Value of Tumor Budding in Laryngeal Carcinoma by Conventional and Immunohistochemical Staining

Table 5

Summary of the three studies that examined the prognostic value of tumor budding in laryngeal SCC in comparison to the current study.

Points of comparison	Sarioglu et al., 2010 [21]	Ekmekci et al., 2019 [20]	Boxberg et al., 2019 [22]	Current study
Number of cases	64 cases of laryngeal SCC	77 cases of laryngeal SCC	157 cases of laryngeal and hypopharyngeal SCC	118 cases of laryngeal SCC
Study design	Retrospective	Retrospective	Retrospective	Retrospective
Previous neoadjuvant therapy prior to surgery	Not specified	Not specified	Among exclusion criteria	Among exclusion criteria
Staining	H&E only	H&E only	H&E only	H&E+IHC by Ck; Only moderate agreement between the two staining methods ()
Cutoff for presence or absence of tumor budding	≥1 tumor cell and <5 tumor cells	≥1 tumor cell and <5 tumor cells	≥1 tumor cell and <5 tumor cells	≥1 tumor cell and <5 tumor cells
Intensity (extent) of tumor budding	According to Kanazawa et al., 2008	According to Kanazawa et al., 2008	A new technique suggested by the authors	According to Kanazawa et al., 2008
Survival analysis	O.S., locoregional disease-free, and distant metastasis disease-free survival	Not done	O.S., disease specific, and disease-free survival	O.S. and progression-free survival
Univariate analysis of relation between tumor budding and survival	Tumor budding is significantly associated with distant metastasis-free survival	____	Tumor budding activity is significantly associated with O.S., disease specific, and disease-free survival	Tumor budding is significantly associated with O.S. and progression-free survival
Multivariate analysis of prognostic factors and survival	Tumor budding and metastatic lymph nodes are associated with distant metastasis-free survival	___	The proposed new grading system (that incorporates tumor budding activity and cell nest size) and metastatic lymph nodes are associated with O.S., disease free, and disease-specific survival	Tumor budding, metastatic lymph nodes and vascular invasion are associated with progression-free survival

According to Kanazawa et al., 2008. Budding intensity was classified as follows: examined to choose the largest section of the whole lesion. Budding was classified as follows: mild = budding at ≤1/3 of the entire margin; moderate = budding at 1/3-2/3 of the margin; marked = budding at ≥2/3 of invasive margin. A new technique for evaluating budding activity suggested by Boxberg et al., 2019 in their study: assessed in 10 continuous HPFs in areas showing maximal budding; such that low budding activity was defined as 1 to 14 budding nests and high budding activity as ≥15 budding nests, respectively. SCC: squamous cell carcinoma; IHC: immunohistochemistry; Ck: pancytokeratin.