Hyaluronidases and hyaluronan synthases expression is inversely correlated with malignancy in lung/bronchial pre-neoplastic and neoplastic lesions, affecting prognosis.
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.
Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
V K de
VK
Sá
Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
T P
TP
Rocha
Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Al
A
Moreira
Departamento de Anatomia Patológica, A.C. Camargo Cancer Center, São Paulo, SP, Brasil.
F A
FA
Soares
Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
T
T
Takagaki
Universidade de Coimbra, Coimbra, Portugal.
L
L
Carvalho
NHS Foundation Trust, National Heart and Lung Division, Imperial College, London, UK.
A G
AG
Nicholson
Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
V L
VL
Capelozzi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001984:Bronchial Neoplasms / Q000201:enzymology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000032:analysis; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D000076002:Hyaluronan Synthases; D006821:Hyaluronoglucosaminidase / Q000032:analysis / Q000378:metabolism*; D006965:Hyperplasia / Q000201:enzymology; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008679:Metaplasia / Q000201:enzymology; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology; D011379:Prognosis; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; D006821:Hyaluronoglucosaminidase; C066852:hyaluronidase PH-20