Epithelial cell proliferation, apoptosis, and apoptosis inhibition in inverted papillomas.

Inverted papillomas (IPs) are rare benign tumors of nasal epithelium with high recurrence rates and malignant transformation potential. Their etiology is still uncertain, and the mechanism of their growth has not yet been fully described. The purpose of this study was to detect, quantify, and compare cell proliferation, apoptosis, and apoptosis inhibition in hyperplastic epithelium from IPs and in inflammatory nasal polyps (NPs). IP samples were obtained after surgical removal of tumor in 13 patients, and NPs were sampled during endoscopic ethmoidectomy in 10 patients with nasal polyposis. Cell proliferation and apoptosis inhibition, respectively, were assessed by immunohistochemical identification of the proliferating cell nuclear antigen (PCNA) and the oncoprotein Bcl-2. Apoptosis was evaluated by analyzing the DNA fragmentation. Cell proliferation and apoptosis were significantly higher in IPs than in NPs (P = .0002 and P = .043, respectively), while apoptosis inhibition was significantly lower in IPs than in NPs (P = .001). Concerning IPs, cell proliferation was significantly higher than apoptosis (P = .0029) and apoptosis inhibition (P = .0015). The increase in epithelial cell proliferation seemed to be greater in IPs with dysplasia than in IPs without dysplasia. Increased epithelial cell proliferation, but not apoptosis and apoptosis inhibition, seems to be involved in the development of IP.

Myofibroblast accumulation induced by transforming growth factor-beta is involved in the pathogenesis of nasal polyps.

Myofibroblasts that express alpha-smooth muscle actin (alpha-SMA) are detected in many chronic inflammatory diseases. Transforming growth factor-beta (TGF-beta) is a potent inducer of myofibroblast accumulation in tissues. In this study, scattered myofibroblasts and TGF-beta were quantified and localized in nasal polyps (NPs) and normal nasal mucosa (NM). NPs were sampled in 16 patients during ethmoidectomy and NM was obtained from 10 control subjects during rhinoplasty. alpha-SMA and TGF-beta were detected using immunohistochemistry and the numbers of labeled cells were quantified (alpha-SMA and TGF-beta indices) and compared between NPs and NM. In eight NPs, in which the pedicle was preserved, alpha-SMA and TGF-beta were evaluated and compared in the pedicle, central, and tip areas. Finally, TGF-beta expression was compared between low (zone 1), moderate (zone 2), and high (zone 3) zones of alpha-SMA positivity. alpha-SMA and TGF-beta indices were significantly higher in NPs than in NM. In the eight selected NPs, alpha-SMA-positive cells were significantly more abundant in the pedicle than in the central and tip areas, whereas TGF-beta-positive cells were significantly more numerous in the pedicle than in the tip area. The number of TGF-beta-positive cells was significantly higher in zone 3 than in zone 1 of alpha-SMA positivity. Myofibroblasts, which are abundant in NPs but rare in NM, could be involved in the growth of NPs by inducing extracellular matrix accumulation. The local development of myofibroblasts in NPs could be controlled by TGF-beta, locally produced by inflammatory cells.