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Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy.

Rangel MP, de Sá VK, Martins V, Martins JR, Parra ER, Mendes A, Andrade PC, Reis RM, Longatto-Filho A, Oliveira CZ, Takagaki T, Carraro DM, Nader HB, Capelozzi VL - Braz. J. Med. Biol. Res. (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.

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.

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A, Box plots of hyaluronan (HA) in healthy volunteers,cancer-free patients and lung cancer patients (LC). Patients with lung cancer hadsignificantly higher HA levels in sputum than in the cancer-free patients andhealthy volunteers (Log10 scale; P<0.001, Mann-Whitney test).B, Box plots of HA in lung cancer patients. Patients withsquamous cell carcinoma (SqCC) had higher HA levels compared to adenocarcinoma(AD) and large cell carcinoma (LCC) (log10 scale; P<0.001, Kruskal-Wallistest). C, D, Receiver operating characteristic(ROC) curves for sputum levels of HA. C, The cut-off level of HAthat resulted in the highest diagnostic accuracy was >31.44 ng/mg. This cut-offpoint discriminated between healthy controls and lung cancer patients, with 100%specificity and 51% sensitivity. The diagnostic accuracy was 82%.D, The cut-off level of HA that discriminated cancer-freepatients and lung cancer patients with 100% specificity and 33% sensitivity was>48.3 ng/mg. The diagnostic accuracy was 69%.
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f02: A, Box plots of hyaluronan (HA) in healthy volunteers,cancer-free patients and lung cancer patients (LC). Patients with lung cancer hadsignificantly higher HA levels in sputum than in the cancer-free patients andhealthy volunteers (Log10 scale; P<0.001, Mann-Whitney test).B, Box plots of HA in lung cancer patients. Patients withsquamous cell carcinoma (SqCC) had higher HA levels compared to adenocarcinoma(AD) and large cell carcinoma (LCC) (log10 scale; P<0.001, Kruskal-Wallistest). C, D, Receiver operating characteristic(ROC) curves for sputum levels of HA. C, The cut-off level of HAthat resulted in the highest diagnostic accuracy was >31.44 ng/mg. This cut-offpoint discriminated between healthy controls and lung cancer patients, with 100%specificity and 51% sensitivity. The diagnostic accuracy was 82%.D, The cut-off level of HA that discriminated cancer-freepatients and lung cancer patients with 100% specificity and 33% sensitivity was>48.3 ng/mg. The diagnostic accuracy was 69%.

Mentions: The concentration levels of HA in sputum obtained from 90 patients with LC, 25cancer-free patients, and 15 healthy volunteers are shown in Table 3. HA concentration levels were significantly increased insputum from LC patients compared to cancer-free and healthy volunteers (P<0.001,Figure 2A). HA levels were higher in the sputumof patients with SqCC compared to other histological types (P=0.01; Table 3, Figure2B).


Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy.

Rangel MP, de Sá VK, Martins V, Martins JR, Parra ER, Mendes A, Andrade PC, Reis RM, Longatto-Filho A, Oliveira CZ, Takagaki T, Carraro DM, Nader HB, Capelozzi VL - Braz. J. Med. Biol. Res. (2015)

A, Box plots of hyaluronan (HA) in healthy volunteers,cancer-free patients and lung cancer patients (LC). Patients with lung cancer hadsignificantly higher HA levels in sputum than in the cancer-free patients andhealthy volunteers (Log10 scale; P<0.001, Mann-Whitney test).B, Box plots of HA in lung cancer patients. Patients withsquamous cell carcinoma (SqCC) had higher HA levels compared to adenocarcinoma(AD) and large cell carcinoma (LCC) (log10 scale; P<0.001, Kruskal-Wallistest). C, D, Receiver operating characteristic(ROC) curves for sputum levels of HA. C, The cut-off level of HAthat resulted in the highest diagnostic accuracy was >31.44 ng/mg. This cut-offpoint discriminated between healthy controls and lung cancer patients, with 100%specificity and 51% sensitivity. The diagnostic accuracy was 82%.D, The cut-off level of HA that discriminated cancer-freepatients and lung cancer patients with 100% specificity and 33% sensitivity was>48.3 ng/mg. The diagnostic accuracy was 69%.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4470316&req=5

f02: A, Box plots of hyaluronan (HA) in healthy volunteers,cancer-free patients and lung cancer patients (LC). Patients with lung cancer hadsignificantly higher HA levels in sputum than in the cancer-free patients andhealthy volunteers (Log10 scale; P<0.001, Mann-Whitney test).B, Box plots of HA in lung cancer patients. Patients withsquamous cell carcinoma (SqCC) had higher HA levels compared to adenocarcinoma(AD) and large cell carcinoma (LCC) (log10 scale; P<0.001, Kruskal-Wallistest). C, D, Receiver operating characteristic(ROC) curves for sputum levels of HA. C, The cut-off level of HAthat resulted in the highest diagnostic accuracy was >31.44 ng/mg. This cut-offpoint discriminated between healthy controls and lung cancer patients, with 100%specificity and 51% sensitivity. The diagnostic accuracy was 82%.D, The cut-off level of HA that discriminated cancer-freepatients and lung cancer patients with 100% specificity and 33% sensitivity was>48.3 ng/mg. The diagnostic accuracy was 69%.
Mentions: The concentration levels of HA in sputum obtained from 90 patients with LC, 25cancer-free patients, and 15 healthy volunteers are shown in Table 3. HA concentration levels were significantly increased insputum from LC patients compared to cancer-free and healthy volunteers (P<0.001,Figure 2A). HA levels were higher in the sputumof patients with SqCC compared to other histological types (P=0.01; Table 3, Figure2B).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.

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.

Show MeSH
Related in: MedlinePlus