20 research outputs found
Mesotheliomas show higher hyaluronan positivity around tumor cells than metastatic pulmonary adenocarcinomas
Hyaluronan is a unique glycosaminoglycan
of the extracellular matrix, abundant in normal
connective tissues but highly increased in many
pathological conditions like cancer. Mesothelioma, one
of the most malignant cancer types, is associated with
high content of hyaluronan, with elevated levels of
hyaluronan in pleural effusions and serum of the
patients. Metastatic lung adenocarcinomas are typically
less aggressive and have a better prognosis as compared
to mesotheliomas, a reason why it is highly important to
find reliable tools to differentiate these cancer types.
The main purpose of this study was to evaluate the
amount of hyaluronan, hyaluronan producing synthases
(HAS’s) and hyaluronan receptor CD44, in mesothelioma and metastatic lung adenocarcinomas.
Furthermore, we wanted to clarify the role of hyaluronan, CD44 and HAS’s as putative markers for
differentiating malignant mesothelioma from metastatic
lung adenocarcinomas.
The main finding of this study was that
mesotheliomas are significantly more positive for
hyaluronan staining than metastatic adenocarcinomas.
Unexceptionally, a trend of CD44 positivity of stromal
cells was higher in adenocarcinomas as compared to
mesotheliomas. However, no statistically significant
differences were found between the staining of any of
the HAS isoenzymes either in tumor cells or stromal
cells of different groups of cases.
The results show that there are significant
differences in hyaluronan content between metastatic
lung adenocarcinomas and mesotheliomas. However, as
previous studies have suggested, hyaluronan alone is not
a sufficient independent marker for diagnostic
differentiation of these cancer types, but could be
utilized as a combination together with other specific
markers
GASC1 expression in lung carcinoma is associated with smoking and prognosis of squamous cell carcinoma
GASC1 (gene amplified in squamous cell
carcinoma 1) encodes a nuclear protein that
epigenetically catalyses the lysine demethylation of
histones.
We investigated the expression of GASC1 in
different histological subtypes of lung cancer (n=289).
Percentage value of GASC1 immunohistochemical
expression was evaluated separately in the nuclei and
cytoplasms of epithelial cancer cells. The results were
compared with clinicopathologic factors and the
smoking history of the patients.
In lung tumor cells, 38% of nuclei and 54% of the
cytoplasms stained positive for GASC1. Adenocarcinomas
expressed more GASC1 nuclear (p=0.00011)
and cytoplasmic (p=0.00074) positivity than squamous
cell carcinoma. Smokers displayed less nuclear and
cytoplasmic GASC1 expression than non-smokers
(p=0.028 and p=0.036, respectively). Similarly, patients
with more cytoplasmic positive staining had fewer pack
years (p=0.043). Nuclear GASC1 expression had an
impairing effect on survival when all histological lung
cancer types were analysed together (p=0.039) and
separately in squamous cell lung carcinoma (p=0.016).
The results reveal that GASC1 expression is higher
in adenocarcinoma than squamous cell carcinoma.
Smoking decreases GASC1 expression in tumor cells,
indicating that tobacco smoke may influence the
methylation of histone 3 lysine residues in lung cancer.
Nonetheless, nuclear GASC1 predicts a poor prognosis,
especially in squamous cell carcinoma
Snail promotes an invasive phenotype in lung carcinoma
Abstract Background Snail is a transcriptional factor which is known to influence the epitheliomesenchymal transition (EMT) by regulating adhesion proteins such as E-cadherin and claudins as well as matrix metalloproteases (MMP). Methods To evaluate the functional importance of snail, a transciptional factor involved in EMT in lung tumors, we investigated its expression in a large set of lung carcinomas by immunohistochemistry. Expression of snail and effects of snail knockdown was studied in cell lines. Results Nuclear snail expression was seen in 21% of cases this being strongest in small cell lung carcinomas (SCLC). There was significantly greater snail expression in SCLC compared to squamous cell or adenocarcinoma. Positive snail expression was associated with poor survival in the whole material and separately in squamous cell and adenocarcinomas. In Cox regression analysis, snail expression showed an independent prognostic value in all of these groups. In several cell lines knockdown of snail reduced invasion in both matrigel assay and in the myoma tissue model for invasion. The influence of snail knockdown on claudin expression was cell type specific. Snail knockdown in these cell lines modified the expression of MMP2 and MMP9 but did not influence the activation of these MMPs to any significant degree. Conclusions The results show that snail plays an important role in the invasive characteristics of lung carcinoma influencing the survival of the patients. Snail knockdown might thus be one option for targeted molecular therapy in lung cancer. Snail knockdown influenced the expression of claudins individually in a cell-line dependent manner but did not influence MMP expressions or activations to any significant degree.</p