Mutation and expression of the metastasis suppressor gene KAI1 in esophageal squamous cell carcinoma.
BACKGROUND
KAI1/CD82, a tumor metastasis suppressor gene, is correlated inversely with the progression and invasion of several tumors. It also has been reported that the KAI1 gene is related to the tumor suppressor gene p53. This study was performed to clarify the correlation between KAI1/CD82 expression and clinicopathologic characteristics and p53 expression in patients with esophageal squamous cell carcinoma (ESCC). The authors also investigated mutation of the KAI1 gene coding region to determine whether this may reduce KAI1 expression in ESCC.


METHODS
Using immunohistochemistry with anti-KAI1 polyclonal antibody and monoclonal antibody against p53, KAI1/CD82 and p53 expression were detected in 55 patients with ESCC who had undergone surgery. The authors examined the KAI1 gene mutation in 22 patients with ESCC by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and DNA sequencing.


RESULTS
KAI1/CD82 expression was positive in 36 of 55 patients (65.5%). There was a significant inverse correlation between KAI1/CD82 expression and regional lymph node metastasis (P = 0.0045), distant metastasis (P = 0.0092), the number of lymph node metastases (P = 0.0019), and pathologic stage (P = 0.0046). The survival rates of KAI1/CD82 negative patients were poorer than those of positive patients (P = 0. 024). The correlation between KAI1 positive and p53 positive tumors was not statistically significant. None of the 22 patients with ESCC showed mutation of the KAI1 gene by PCR-SSCP. In one patient, there was polymorphism in the SSCP assay and DNA sequencing.


CONCLUSIONS
The authors demonstrated immunohistochemically that the expression of KAI1 protein appeared to be correlated with lymph node metastasis. Mutation does not seem to be a mechanism for dysregulation of the KAI1 protein in ESCC.
Miyazaki
T
T
Department of Surgery I, Gunma University School of Medicine, Japan.
Kato
H
H
Shitara
Y
Y
Yoshikawa
M
M
Tajima
K
K
Masuda
N
N
Shouji
H
H
Tsukada
K
K
Nakajima
T
T
Kuwano
H
H
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D004273:DNA, Neoplasm / Q000032:analysis; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051861:Kangai-1 Protein; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D015703:Antigens, CD; C497688:CD82 protein, human; D004273:DNA, Neoplasm; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53