Hyaluronidases and hyaluronan synthases expression is inverselycorrelated with malignancy in lung/bronchial pre-neoplastic and neoplastic lesionsaffecting prognosis

摘要

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 higherin pre-neoplastic lesions than in neoplastic lesions. Comparative Cox multivariateanalysis controlled by N stage and histologic tumor type showed that patients withhigh HAS-3 expression in pre-neoplastic cells obtained by lung/bronchial biopsypresented a significantly higher risk of death (HR=1.19; P=0.04). We concluded thatlocalization of Hyal and HAS in lung/bronchial pre-neoplastic and neoplastic lesionswas inversely related to malignancy, which implied that visualizing these factorscould be a useful diagnostic procedure for suspected lung cancer. Finalizing thisconclusion will require a wider study in a randomized and prospective trial.