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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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Related in: MedlinePlus

Kaplan-Meier plots of survival probability vs follow-up timein months for all patients. The group with <692.1 μg/mg HA appears as the topcurve, and the group with ≥692.1 μg/mg HA appears as the bottom curve.
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f03: Kaplan-Meier plots of survival probability vs follow-up timein months for all patients. The group with <692.1 μg/mg HA appears as the topcurve, and the group with ≥692.1 μg/mg HA appears as the bottom curve.

Mentions: At the end of the follow-up, 32 patients of 46 (69.5%) who underwent surgical resectiondied because of LC. Univariate survival analysis showed that the significant predictorsof overall survival (OS) were N stage (χ2=4.3; P=0.03) and HA expression incancer cells (χ=25.2; P=0.02). A high percentage of HA-positive cellspredicted a shortened disease-free survival [n=11 (47.8%), P=0.02] in univariateanalysis together with stage (P=0.02). However, among ADs, there was a trend toward poorOS, with tumors showing a high percentage of cancer cell-associated HA (P=0.09).Comparative Cox multivariate analysis controlled by gender, age, and AD showed asignificant association between better survival and low cancer cell-associated HA sign(HR=0.08; P=0.03). We ranked the cases according to ROC curve into two groups withdistinctly different average survival times as illustrated by Kaplan-Meier plots inFigure 3. The group with <692.1 μg/mg HAappears as the top curve, and their median survival time was 72 months. Those with≥692.1 μg/mg HA (bottom curve) had a median survival time of just 52 months aftersurgery (log rank=5.3; P=0.02).


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)

Kaplan-Meier plots of survival probability vs follow-up timein months for all patients. The group with <692.1 μg/mg HA appears as the topcurve, and the group with ≥692.1 μg/mg HA appears as the bottom curve.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f03: Kaplan-Meier plots of survival probability vs follow-up timein months for all patients. The group with <692.1 μg/mg HA appears as the topcurve, and the group with ≥692.1 μg/mg HA appears as the bottom curve.
Mentions: At the end of the follow-up, 32 patients of 46 (69.5%) who underwent surgical resectiondied because of LC. Univariate survival analysis showed that the significant predictorsof overall survival (OS) were N stage (χ2=4.3; P=0.03) and HA expression incancer cells (χ=25.2; P=0.02). A high percentage of HA-positive cellspredicted a shortened disease-free survival [n=11 (47.8%), P=0.02] in univariateanalysis together with stage (P=0.02). However, among ADs, there was a trend toward poorOS, with tumors showing a high percentage of cancer cell-associated HA (P=0.09).Comparative Cox multivariate analysis controlled by gender, age, and AD showed asignificant association between better survival and low cancer cell-associated HA sign(HR=0.08; P=0.03). We ranked the cases according to ROC curve into two groups withdistinctly different average survival times as illustrated by Kaplan-Meier plots inFigure 3. The group with <692.1 μg/mg HAappears as the top curve, and their median survival time was 72 months. Those with≥692.1 μg/mg HA (bottom curve) had a median survival time of just 52 months aftersurgery (log rank=5.3; P=0.02).

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