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 and metastasis has been reported for several kinds of cancer, but the mechanism of this down‐regulation is not known. In the present study, our aim was to ascertain the relationship between down‐regulation of KAI1 mRNA expression and KAI1 gene alterations in lung cancer. Forty‐nine cases of adenocarcinoma of the lung were studied by reverse‐transcriptase polymerase chain reaction (RT‐PCR) assay of KAI1 mRNA and by immunohistochemical detection of KAI1 protein. In addition, markers of the microsatellite loci D11S1344 and D11S1326 were used to investigate loss of heterozygosity (LOH) and replication errors (RERs) of the KAI1 gene region. The RT‐PCR assay showed that there was no correlation between KAI1 mRNA expression and either the age of the patients or tumor size. By contrast, KAI1 mRNA expression was significantly 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 pathological 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 informative cases 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 at these loci. These results suggest that down‐regulation of KAI1 mRNA expression rarely if ever involves LOH or RERs of the KAI1 gene region in primary lung adenocarcinoma.