| Abstract: | ![]()
We collected a series of 136 lung/bronchial and 56 matched lung parenchyma tissuesamples from patients who underwent lung/bronchial biopsies and presented invasivecarcinoma after lung surgery. The lung/bronchial samples included basal cellhyperplasia, squamous metaplasia, moderate dysplasia, adenomatous hyperplasia, severedysplasia, squamous cell carcinoma and adenocarcinoma. Matched lung parenchyma tissuesamples 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 showedsignificantly 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 inbasal cell hyperplasia (P=0.01) or moderate dysplasia (P=0.02). HAS-2 wassignificantly higher in severe dysplasia (P=0.002) and in squamous metaplasia(P=0.04) compared with basal cell hyperplasia. HAS-3 was significantly expressed inbasal cell hyperplasia compared with atypical adenomatous hyperplasia (P=0.05) andsevere dysplasia (P=0.02). Lower expression of HAS-3 was found in severe dysplasiacompared 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. |
