From laryngeal epithelial precursor lesions to squamous carcinoma of the larynx: the role of cell cycle proteins and β-catenin

Abstract

Novel markers to accurately predict the risk of malignant transformation in laryngeal epithelial precursor lesions (EPL) are needed. We tried to identify some molecular alterations occurring in laryngeal tumorigenesis. In this study, 60 paraffin-embedded EPL and 17 metachronous invasive carcinomas were immunostained for markers associated with proliferation (Ki67), cell cycle control (p53, p21, p16, p27, cyclin D1), and cell adhesion and invasion (laminin and β-catenin). Aberrant expression of p16 and p53 and positivity at cytoplasm for β-catenin and cyclin D1 were detected significantly in EPL with progression to invasive laryngeal carcinoma. All cases with basal and suprabasal reactivity of p53 showed β-catenin overexpression. We found that β-catenin protein expression increased significantly with the grade of dysplasia. This is one of the studies with the largest number of laryngeal EPL and invasive carcinoma studied sequentially. Our data confirm the role of some cell cycle regulatory proteins in the development of laryngeal carcinoma. Cytoplasmic retention of β-catenin in EPL seems to be related with more aggressive biological behavior. Combined increased p53 and cytoplasmic β-catenin protein expression could be biologically important in laryngeal tumorigenesis. Further research is required to clarify the involvement of β-catenin in the mechanism associated with malignant transformation in laryngeal tissues.

Predictive value of CCND1/cyclin D1 alterations in the malignant transformation of potentially malignant head and neck disorders: Systematic review and meta‐analysis

“…After excluding studies not meeting the inclusion criteria, nine articles were finally entered in the review for qualitative evaluation and quantitative meta-analysis. 24,25,[29][30][31][42][43][44][45] 3.2 | Study characteristics Table 1 summarizes the characteristics of the nine studies selected, which reported on a total of 496 patients with malignant transformation of head and neck PMDs; sample sizes ranged between 28 and 90 patients. Cyclin D1 overexpression was addressed by seven studies and CCND1 amplification by two.…”

“…When RR data were not reported, odds ratios (ORs) were extracted as an approximation of this measure . In order to facilitate the interpretation of results, we performed sensitivity analyses in which the meta‐analysis was repeated, first omitting studies calculating RRs, and then those calculating ORs …”

“…The general results did not appreciably change after sequential repetition of the meta-analysis with the omission of one study at a time, indicating that the combined estimations reported do not depend on the influence of a particular individual study ( Figure 4A). As reported above, we also repeated the meta-analyses, first omitting studies calculating RRs, 24,25,[29][30][31]42,43 and then those calculating ORs. 44,45 The results were only changed when the studies used OR were combined ( Table 2), which may in part explain the moderate heterogeneity found.…”

“…16,20 CCND1/cyclin D1 alterations in early stages of head and neck carcinogenesis have been widely reported, [21][22][23][24] and increased cyclin D1 expression has been associated with higher degrees of dysplasia. 19,25,26 It has therefore been hypothesized that its elevated expression may serve as a predictive biomarker for the malignant transformation of PMD to HNSCC; however, most of the above studies have had a cross-sectional design, limiting conclusions on the risk of developing the disease or on the causal nature of relationships observed. 27,28 With this background, we carried out this systematic review and meta-analysis to qualitatively and quantitatively evaluate published evidence on the predictive value of CCND1 amplification and cyclin D1 overexpression for the malignant transformation of head and neck PMDs.…”

“…Abbreviations: CI, confidence intervals; OR, odds ratio; PMDs, potentially malignant disorders; R, random-effects model; RR, risk ratio; SM, submucous fibrosis; Stat., statistical.Two sensitivity analyses were conducted. The meta-analysis was repeated, first omitting the studies reporting RRs24,25,[29][30][31]42,43 and then those reporting ORs.…”