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.

N-cadherin and hyaluronan expression in head and neck squamous cell carcinoma, relation to patient outcomes

“…[16,70,71] The current study indicated a strong intensity of stromal and tumoral HA expression was significantly (p < .05) associated with the presence of nodal metastasis. A similar finding was reported by Wernicke et al, Suwiwat et al, Afify et al [16,56,[70][71][72] Regarding incidence of recurrence, 58.6% of cases with a positive history of recurrence revealed strong tumor and stromal HA expression but was not statistically significant by chi-square test (p values .06 and .07). Kaplan Meier curves demonstrated a statistically significant difference of stromal HA intensity of expression in relation to DFS (p = .050).…”

“…[54] Also, previous few studies reported high levels of in HNSCC. [55,56] In contrast, the HA expression is low in melanoma, and its absence is significantly correlated with the metastatic potential. [57,58] Accumulation of HA can decrease tumorigenic potential and confer resistance to cancer.…”

“…In agreement with our finding, many studies indicated high HA levels associated with poor prognosis and shorter patient survival. [16,46,56,[70][71][72][73] …”

Glioma infiltration and extracellular matrix: key players and modulators

“…HA levels can be increased around the tumor cells themselves or within the tumor stroma (Itano, Zhuo, & Kimata, ). However, as with other highly differentiated tumors such as lung, breast, colon and prostate cancer, astrocytomas express increased amounts of HA in both tumor epithelia and intratumoral areas (Boregowda et al, ; Josefsson et al, ; Misra et al, ; Rangel et al, ; Schwertfeger, Cowman, Telmer, Turley, & McCarthy, ; Wiranowska & Rojiani, ).…”

Relevância dos proteoglicanos como biomarcadores prognósticos e preditivos em carcinomas não-pequenas células e seu impacto na carcinogênese pulmonar

“…Tese de doutorado -USP Em diversos tipos de câncer, proteínas intracelulares e de MEC têm se mostrado como potenciais marcadores diagnósticos presentes em secreções, principalmente no sangue, na saliva, no escarro e na urina (Melo et al, 2015;Franzmann et al, 2011;Rangel et al, 2015;Paserotti et al, 2006).…”