Morphometric analysis of Ki-67 and p16 expression in laryngeal precursor lesions

Abstract

Laryngeal precursor lesions represent areas of altered epithelium with an increased likelihood for progression to squamous cell carcinoma. The exact molecular mechanisms of malignant transformation of laryngeal mucosa are not completely clear, but are certainly due to deregulation of cell proliferation. To assess the potential value of the p16 and Ki-67 as markers of malignant progression, we undertook a retrospective immunohistochemical and morphometric analysis on biopsy specimens from patients with precancerous lesions in the larynx. Morphometric analysis of samples stained with p16 antibody showed epithelial cell positivity in 29 (100 %) of samples with simple hyperplasia, 31 (100 %) samples with basal/parabasal cell hyperplasia, 23 (88 %) samples with atypical hyperplasia and 20 (95 %) samples with in situ carcinoma. There was a significant difference in percentage of p16-positive cells between samples with simple hyperplasia and samples with in situ carcinoma. Morphometric analysis of samples stained with Ki-67 antibody showed epithelial cell positivity in 27 (93 %) of samples with simple hyperplasia, 30 (97 %) samples with basal/parabasal cell hyperplasia, 26 (100 %) samples with atypical hyperplasia and 18 (86 %) samples with in situ carcinoma. There was a significant difference not only in the percentage of Ki-67-positive cells between samples with simple hyperplasia and samples with in situ carcinoma, but also between samples with simple and basal/parabasal cell hyperplasia. Laryngeal epithelial precursor lesions show significantly opposite patterns in p16 and Ki-67 immunopositivity. Simple hyperplasia on average shows 12 % of Ki-67-positive cells and 46 % of p16-positive cells. In situ carcinoma on average shows 23 % of Ki-67-positive cells and 36 % of p16-positive cells.

Histologic correlation of expression of Ki-67 in squamous cell carcinoma of the glottis according to the degree of cell differentiation

“…Of these lesions, carcinoma in situ tends to have a higher positivity than isolated hyperplasias. 22 …”

Loss of Estrogen Receptors is Associated with Increased Tumor Aggression in Laryngeal Squamous Cell Carcinoma

“…Effort has been directed to identify molecular biomarkers that will enable the stratification of risk for malignant transformation and aggressive tumor behavior in patients with precancerous lesions. Some proposed biomarkers include the presence of chromosome instability markers 42 , cell cycle proteins 43 , β-catenin 44 , and microRNA-21 45 .…”