Aviel-Ronen S et al. - In a trial to evaluate glypican-3 expression in lung cancer at the protein and mRNA levels and correlate it with clinical, histological and genomic characteristics such as RAS mutation status, it was found that glypican-3 was overexpressed in cancerous vs normal lung tissue. Adenocarcinoma and squamous cell carcinoma had differential expression of glypican-3, with predilection to squamous cell carcinoma pts who smoked. Glypican-3 expression in squamous cell carcinoma as an oncofetal protein renders it a potential candidate marker for early detection of lung squamous cell carcinoma Methods
Immunohistochemistry was used on tissue microarray to study glypican-3 expression in 97 pts, evaluated glypican-3 mRNA levels by quantitative polymerase chain reaction in 143 pts, and identified RAS mutations by allele-specific oligonucleotide hybridization
Results were correlated with clinical and histological data
Results
Glypican-3 immunostaining was negative in all normal lung tissues, but positive in 23% of lung carcinoma samples
High protein and mRNA expression was associated with squamous histology
RAS mutations were highly associated with adenocarcinoma and low glypican-3 mRNA expression
Among smokers, glypican-3 mRNA expression was reduced in adenocarcinoma patients, and was elevated in those with squamous cell carcinoma
These opposing associations also correlated with smoking burden
Pts with tumors staining positively for glypican-3 smoked significantly more than pts with tumors staining negatively
No association was found between glypican-3 expression and pt outcome
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