The extrinsic apoptotic signaling pathway in gastric adenocarcinomas assessed by tissue microarray

The purpose of this investigation was to analyze the immunoexpression of FasL, Fas, FADD, cleaved caspase 8, and cleaved caspase 3 in gastric cancer. Formalin-fixed and paraffin-embedded gastric adenocarcinoma tissues from 87 patients, including adjacent normal tissues, were included on tissue micro...

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Published in:Pathology, research and practice research and practice, 2011-10, Vol.207 (10), p.613-617
Main Authors: Gomes, Thiago S., Oshima, Celina T.F., Segreto, Helena R.C., Barrazueta, Luis M., Costa, Henrique O., Lima, Flavio O., Forones, Nora M., Ribeiro, Daniel A.
Format: Article
Language:English
Subjects:
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Adult
Aged
Aged, 80 and over
Apoptosis
Apoptosis - physiology
Caspase 3 - analysis
Caspase 8 - analysis
Fas Ligand Protein - analysis
fas Receptor - analysis
Fas-Associated Death Domain Protein - analysis
Female
Gastric cancer
Humans
Immunohistochemistry
Male
Middle Aged
Neoplasm Staging
Signal Transduction - physiology
Stomach Neoplasms - metabolism
Stomach Neoplasms - pathology
Tissue Array Analysis
TMA
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Summary:The purpose of this investigation was to analyze the immunoexpression of FasL, Fas, FADD, cleaved caspase 8, and cleaved caspase 3 in gastric cancer. Formalin-fixed and paraffin-embedded gastric adenocarcinoma tissues from 87 patients, including adjacent normal tissues, were included on tissue microarray by immunohistochemistry. The tumor and the adjacent normal tissues were positive for FasL in 66.7% and 90.6%, for Fas in 52.8% and 52.4%, for FADD in 67.4% and 82.3%, for cleaved caspase 8 in 27.9% and 37.7%, and for cleaved caspase 3 in 33.7% and 8.3%, respectively. FasL and the FADD from tumor were statistically different in relation to the histological type. Cleaved caspase 8 was statistically different in relation to clinical stage ( p = 0.031). The FADD from normal tissue was statistically different in relation to age ( p = 0.039), sex ( p = 0.055), clinical stage ( p = 0.019), and Fas was different in relation to tumor size ( p = 0.012). In the tumor, we observed a correlation between FasL and Fas, FasL and FADD, and FasL and cleaved caspase 3. In the adjacent normal tissue, a correlation was observed between FasL and Fas, FasL and FADD. There was no association of another marker with sex, age, clinical stage, and survival. Our results suggest that these proteins mediate the early extrinsic apoptotic pathway in gastric cancer and adjacent normal mucosa. FasL protein binds to Fas protein and subsequently binds to death receptor FADD signaling activation of the extrinsic apoptotic pathway. In this phase, there was inhibition of caspase 8 and, consequently, decreased apoptosis.
ISSN:0344-0338
1618-0631
DOI:10.1016/j.prp.2011.06.010