J Korean Med Sci.  2005 Oct;20(5):770-776. 10.3346/jkms.2005.20.5.770.

Tissue Microarray Analysis of Fas and FasL Expressions in Human Non-small Cell Lung Carcinomas; with Reference to the p53 and bcl-2 Overexpressions

• Myong NH

• KMID: 1781759
• DOI: http://doi.org/10.3346/jkms.2005.20.5.770

Abstract

Lack of surface Fas expression is a main route for apoptotic resistance which is considered an important mechanism of tumorigenesis and tumor progression. Fas and FasL expressions in 110 non-small cell lung carcinomas (NSCLCs) were investigated to evaluate their roles in pulmonary carcinogenesis and to examine the clinicopathologic significance of Fas expression with its relationship with p53 and bcl-2 overexpressions. Immunohistochemical analysis using tissue microarray demonstrated that a large proportion of NSCLC patients (60%) showed lack of membranous Fas expression. The Fas-negative cases revealed the significantly lower survival rate than Fas-positive ones. Also, the loss of Fas receptor expression was found more frequently in advanced stage and higher nodal status. FasL protein was increased in most NSCLCs (89%) compared to normal lungs. p53 and bcl-2 overexpressions showed no association with Fas expression. Conclusively, reduced membranous Fas expression as a mechanism of apoptotic resistance is considered to play an important part of the pulmonary carcinogenesis, which may predict poor survival and have a bad prognostic influence. Increased FasL expression is thought to be a basis for the immune evasion in NSCLCs. The rare bcl-2 overexpression suggests that this anti-apoptotic protein is unlikely to play a role in the apoptotic resistance of NSCLCs.

Keyword

Antigens, CD95; FasL protein; Carcinoma, Non-Small-Cell Lung; Carcinogenesis; Tissue Array Analysis

MeSH Terms

Antigens, CD95/*metabolism
Apoptosis
Carcinoma, Non-Small-Cell Lung/*metabolism/mortality
Cell Survival
Comparative Study
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Korea/epidemiology
Lung Neoplasms/*metabolism/mortality/pathology
Male
Membrane Glycoproteins/*metabolism
Middle Aged
Oligonucleotide Array Sequence Analysis
Prognosis
Proto-Oncogene Proteins c-bcl-2/*metabolism
Research Support, Non-U.S. Gov't
Risk Assessment/methods
Risk Factors
Survival Analysis
Survival Rate
Tumor Markers, Biological/*metabolism
Tumor Necrosis Factors/*metabolism
Tumor Suppressor Protein p53/*metabolism

Figure

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  Fig. 1 The Kaplan-Meier survival curves according to Fas immunostaining for 110 NSCLC patients. Significant difference in survival times was observed between Fas-positive and Fas-negative cases (log rank test p=0.019).

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  Fig. 2 Normal lung tissue reveal distinct membranous immunoreactivity for Fas protein in bronchiolar epithelia and reactive lymphocytes (×400).

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  Fig. 3 Immunohistochemical finding of Fas-negative (A) and Faspositive (B) squamous carcinomas (×400). The Fas-negative carcinoma (A) shows complete loss of surface Fas expression compared to Fas-expressing reactive lymphocytes. The Fas-positive carcinoma (B) reveals diffuse membranous immunopositivity similar to that of adjacent lymphocytes.

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  Fig. 4 A case of well-differentiated adenocarcinoma (B) showing increased FasL expression compared to the normal bronchial epithelia (A). FasL protein is immunohistochemically expressed in the cytoplasms along the cell borders (×400).

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  Fig. 5 Diffuse and strong immunopositivity for nuclear p53 protein in a case of squamous carcinoma (×400).

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  Fig. 6 A rare case of large cell carcinoma with bcl-2 overexpression reveals diffuse perinuclear immunoreactivity for the cytoplasmic bcl-2 protein (×400).

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