title: Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy.
abstract: Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: M P
authors.initials: MP
authors.lastname: Rangel
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: V K
authors.initials: VK
authors.lastname: de Sá
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: V
authors.initials: V
authors.lastname: Martins
authors.affiliation: Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
authors.forename: J R M
authors.initials: JR
authors.lastname: Martins
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: E R
authors.initials: ER
authors.lastname: Parra
authors.affiliation: Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
authors.forename: A
authors.initials: A
authors.lastname: Mendes
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: P C
authors.initials: PC
authors.lastname: Andrade
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, Universidade do Minho, Braga, Portugal.
authors.forename: R M
authors.initials: RM
authors.lastname: Reis
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, Universidade do Minho, Braga, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Longatto-Filho
authors.affiliation: Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, SP, Brasil.
authors.forename: C Z
authors.initials: CZ
authors.lastname: Oliveira
authors.affiliation: Divisão de Pneumologia, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: T
authors.initials: T
authors.lastname: Takagaki
authors.affiliation: A.C. Camargo Cancer Center, São Paulo, SP, Brasil.
authors.forename: D M
authors.initials: DM
authors.lastname: Carraro
authors.affiliation: Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
authors.forename: H B
authors.initials: HB
authors.lastname: Nader
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: V L
authors.initials: VL
authors.lastname: Capelozzi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000032:analysis*; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008175:Lung Neoplasms / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012907:Smoking / Q000009:adverse effects; D013183:Sputum / Q000737:chemistry*; D018709:Statistics, Nonparametric; D017154:Stromal Cells / Q000737:chemistry / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D006820:Hyaluronic Acid