Hyaluronidases and hyaluronan synthases expression is inversely correlated with malignancy in lung/bronchial pre-neoplastic and neoplastic lesions, affecting prognosis

Autor(es)

de Sa, V. K. ^[1] ; Rocha, T. P. ^[1] ; Moreira, A. L. ^[2] ; Soares, F. A. ^[3] ; Takagaki, T. ^[4] ; Carvalho, L. ^[5] ; Nicholson, A. G. ^{[6, 7]} ; Capelozzi, V. L. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Dept Patol, Sao Paulo, SP - Brazil

^[2] Mem Sloan Kettering Canc Ctr, New York, NY 10021 - USA

^[3] AC Camargo Canc Ctr, Dept Anat Patol, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Fac Med, Inst Coracao, Div Pneumol, Sao Paulo, SP - Brazil

^[5] Univ Coimbra, Coimbra - Portugal

^[6] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, London - England

^[7] Univ London Imperial Coll Sci Technol & Med, Harefield Hosp, NHS Fdn Trust, Natl Heart & Lung Div, London - England

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 48, n. 11, p. 1039-1047, NOV 2015.
• Citações Web of Science: 5

Resumo

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. (AU)

• Processo FAPESP: 11/52095-0 - Avaliação da frequência das mutações EGFR, KRAS e EML4-ALK em adenocarcinomas e seus subtipos e impacto da expressão das hialuronidases e sintases do ácido hialurônico nas lesões pré-neoplásicas pulmonares
• Beneficiário: Vera Luiza Capelozzi
• Modalidade de apoio: Auxílio à Pesquisa - Regular