Down-regulation of KAI1 messenger RNA. expression is not associated with loss of heterozygosity of the KAI1 gene region in lung adenocarcinoma

KAI1, a metastasis suppressor gene of prostate cancer, is located on human chromosome 11p11.2. Down-regulation of KAI1 mRNA during tumor progression a nd metastasis has been reported for several kinds of cancer, but the mechan ism of this down-regulation is not known, In the present study, our aim was to ascertain the relationship between down-regulation of KAI1 mRNA express ion and KAI1 gene alterations in lung cancer Forty-nine cases of adenocarci noma of the lung were studied by reverse-transcriptase polymerase chain rea ction (RT-PCR) assay of KAI1 mRNA and by immunohistochemical detection of K AI1 protein. In addition, markers of the microsatellite loci D11S1344 and D 11S1326 were used to investigate loss of heterozygosity (LOH) and replicati on errors (RERs) of the KAI1 gene region. The RT-PCR assay showed that ther e was no correlation between KAI1 mRNA expression and either the age of the patients or tumor size. By contrast, KAI1 mRNA expression was significantl y correlated with gender (P=0.047), metastasis to the lymph nodes or other organs (P=0.004), the histological grade of the tumor (P=0.036) and the pat hological stage (P=0.049), Immunohistochemical staining showed that in one case without metastasis, loss of KAI1 mRNA was associated with invasion of the stroma by KAI1 protein-negative cancer cells. The numbers of informativ e eases by microsatellite analysis were 14 (28.6%) of 49 at D11S1344 and 27 (55.1%) of 49 at D11S1326; none of 49 adenocarcinomas showed LOH or RERs a t these loci These results suggest that down-regulation of KAI1 mRNA expres sion rarely if ever involves LOH or RERs of the KAI1 gene region in primary lung adenocarcinoma.