Alterations of APC, c-met, and p53 genes in tumor tissue and serum of patients with gastric cancers.
BACKGROUND
Gastric cancer is one of the most significant causes of cancer-related death worldwide. A genetic model consisting of sequential accumulations of alterations in specific genes for gastric cancer has been proposed.


METHODS
The significance of adenomatous polyposis coli (APC) and p53 gene mutations in cancer tissues and their paired serum of 34 gastric cancer patients was investigated using polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP), followed by direct sequencing. c-met mRNA expression was evaluated by reverse-transcription PCR (RT-PCR). Additionally, analyses were carried out to detect the serum carcinoembryonic antigen (CEA) levels, and their correlation to these three molecular markers. Finally, serum molecular markers and their correlation to the presence of postoperative recurrence/metastasis were analyzed.


RESULTS
Of all, 32.4% of patients presented mutations in APC and p53, respectively, and 58.8% presented the overexpression in c-met, overall, at least one of these genetic alterations in 79.4% of tumor tissues. Comparison of three molecular markers showed that the individual detection rate in the serum of patients with tumors harboring the same abnormalities was 18.2, 70.0, and 36.4% for APC, c-met, and p53 genes, respectively. In general, 59.3% of serum from cancerous tissues with gene alterations was demonstrated as positive, whereas all healthy volunteers' sera remained negative. Regarding gene alterations in tumor tissues, c-met overexpression was significantly related to the tumor size (P = 0.017), depth of tumor invasion (P = 0.007), lymph-node metastasis (P < 0.001), and TNM stage (P = 0.001). In the serum, c-met overexpression was closely associated with lymph-node metastasis (P = 0.008) and TNM stage (P = 0.016). The overall positive tumor gene detection rate in the serum was prominently correlated to the serum CEA levels (P = 0.038). In addition, a significantly higher postoperative metastasis/recurrence rate in patients harboring gene mutations with serum molecular markers than those without serum molecular markers was also demonstrated (P = 0.014).


CONCLUSIONS
Our findings suggest that serum molecular markers can be detected in a substantial proportion of gastric cancer patients, and these may offer an auxiliary approach in the noninvasive detection and prognosis of gastric cancer.
Wang
Jaw-Yuan
JY
Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hsieh
Jan-Sing
JS
Chen
Chung-Chi
CC
Tzou
Wen-Shyong
WS
Cheng
Tien-Lu
TL
Chen
Fang-Ming
FM
Huang
Tsung-Jen
TJ
Huang
Yu-Sheng
YS
Huang
Sung-Yu
SY
Yang
Tzufeng
T
Lin
Shiu-Ru
SR
D002272:Carcinoembryonic Antigen / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D017491:Genes, APC; D016158:Genes, p53; D005819:Genetic Markers; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
D002272:Carcinoembryonic Antigen; D005819:Genetic Markers; D019859:Proto-Oncogene Proteins c-met