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.
Highlights
Lung cancer remains the leading cause of cancer death worldwide
We concluded that localization of Hyal and hyaluronan synthases (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
The percentage of Hyal-1 was significantly higher in basal cell hyperplasia compared with moderate dysplasia (P=0.02), adenomatous hyperplasia (P=0.0001), severe dysplasia (P=0.05), squamous cell carcinoma (P=0.0001), and adenocarcinoma (P=0.0001; Figure 3A)
Summary
Lung cancer remains the leading cause of cancer death worldwide. At the time of diagnosis, lung cancer is usually extensive, and despite improvements in therapy, the overall 5-year survival rate for lung cancer patients remains less than 15% [1]. The major reasons for the poor prognosis for lung cancer are the lack of effective screening and early diagnosis procedures, the propensity for early metastasis and the inability of systemic therapies to cure patients with widely metastatic disease [2]. Better understanding of the molecular mechanisms by which these alterations affect lung cancer pathogenesis could provide new diagnostic procedures and prognostic factors for www.bjournal.com.br detection of early-stage or recurrent disease. In this regard, many have investigated molecular markers in pre-neoplastic and neoplastic lesions to gain insight into tumor recurrence and shortened survival [3]. The major mRNA transcript of Hyal-3 is enzymatically inactive and appears to have only a supportive role in Hyal-1 expression [21]
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