Hyaluronidases and hyaluronan synthases expression is inversely correlated with malignancy in lung/bronchial pre-neoplastic and neoplastic lesions, affecting prognosis
Author(s)
Type
Journal Article
Abstract
We collected a series of 136 lung/bronchial and 56 matched lung parenchyma tissue samples from patients who underwent lung/bronchial biopsies and presented invasive carcinoma after lung surgery. The lung/bronchial samples included basal cell hyperplasia, squamous metaplasia, moderate dysplasia, adenomatous hyperplasia, severe dysplasia, squamous cell carcinoma and adenocarcinoma. Matched lung parenchyma tissue samples included 25 squamous cell carcinomas and 31 adenocarcinomas. Immunohistochemistry was performed to analyze for the distribution of hyaluronidase (Hyal)-1 and −3, and hyaluronan synthases (HAS)-1, −2, and −3. Hyal-1 showed significantly higher expression in basal cell hyperplasia than in moderate dysplasia (P=0.01), atypical adenomatous hyperplasia (P=0.0001), or severe dysplasia (P=0.03). Lower expression of Hyal-3 was found in atypical adenomatous hyperplasia than in basal cell hyperplasia (P=0.01) or moderate dysplasia (P=0.02). HAS-2 was significantly higher in severe dysplasia (P=0.002) and in squamous metaplasia (P=0.04) compared with basal cell hyperplasia. HAS-3 was significantly expressed in basal cell hyperplasia compared with atypical adenomatous hyperplasia (P=0.05) and severe dysplasia (P=0.02). Lower expression of HAS-3 was found in severe dysplasia compared with squamous metaplasia (P=0.01) and moderate dysplasia (P=0.01). Epithelial Hyal-1 and −3 and HAS-1, −2, and −3 expressions were significantly higher in pre-neoplastic lesions than in neoplastic lesions. Comparative Cox multivariate analysis controlled by N stage and histologic tumor type showed that patients with high HAS-3 expression in pre-neoplastic cells obtained by lung/bronchial biopsy presented a significantly higher risk of death (HR=1.19; P=0.04). We concluded that localization of Hyal and HAS in lung/bronchial pre-neoplastic and neoplastic lesions was inversely related to malignancy, which implied that visualizing these factors could be a useful diagnostic procedure for suspected lung cancer. Finalizing this conclusion will require a wider study in a randomized and prospective trial.
Date Issued
2015-08-28
Online Publication Date
2015-08-28
2016-10-13T14:37:15Z
Date Acceptance
2015-05-12
ISSN
1678-4510
Publisher
SciELO
Start Page
1039
End Page
1047
Journal / Book Title
Brazilian Journal of Medical and Biological Research
Volume
48
Issue
11
Copyright Statement
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Source Database
web-of-science
Subjects
Science & Technology
Life Sciences & Biomedicine
Biology
Medicine, Research & Experimental
Life Sciences & Biomedicine - Other Topics
Research & Experimental Medicine
Hyaluronidases and hyaluronan synthases
Lung cancer
Pre-neoplastic lung/bronchial lesions
Immunohistochemistry
Morphometry
Prognosis
SQUAMOUS-CELL CARCINOMA
BRONCHIAL EPITHELIUM
CANCER STATISTICS
PROSTATE-CANCER
CD44 RECEPTOR
LUNG-CANCER
GROWTH
TUMORS
ANGIOGENESIS
LOCALIZATION
Adult
Aged
Aged, 80 and over
Bronchial Neoplasms
Carcinoma, Squamous Cell
Cell Adhesion Molecules
Female
Glucuronosyltransferase
Humans
Hyaluronoglucosaminidase
Hyperplasia
Kaplan-Meier Estimate
Lung Neoplasms
Male
Metaplasia
Middle Aged
Multivariate Analysis
Neoplasm Proteins
Precancerous Conditions
Severity of Illness Index
Statistics, Nonparametric
Neurology & Neurosurgery
11 Medical And Health Sciences
Publication Status
Published