Genetic detection of lymph node micrometastases in patients with gastric carcinoma by multiple-marker reverse transcriptase-polymerase chain reaction assay.
BACKGROUND
Some patients with gastric carcinoma experience local disease recurrence despite undergoing curative resection of the tumor and regional lymph nodes (LNs), suggesting the presence of occult micrometastases. To evaluate the presence of gastric carcinoma micrometastasis in patients with otherwise histologically negative LNs, the authors established and tested a multiple-marker reverse transcriptase-polymerase chain reaction (RT-PCR) assay.


METHODS
The authors assessed 435 LNs from 28 patients with gastric carcinoma who underwent gastrectomy with lymphadenectomy using the multiple-marker RT-PCR assay in addition to histologic examination. Carcinoembryonic antigen (CEA), cytokeratin-20 (CK-20), and MAGE-3 gene markers were used in this assay. LNs were scored positive for metastasis if at least one marker was positive. The presence of LN micrometastases also was verified by immunohistochemistry in histologically negative and RT-PCR positive LNs.


RESULTS
Sixty-nine of 435 LNs (16%) were positive for CEA (12%), CK-20 (10%), or MAGE-3 (5%). None of 16 control LNs obtained from disease free patients was positive by RT-PCR assay. Of 414 histologically negative LNs, 50 LNs (12%) were scored as positive for metastasis by the assay. Of 26 patients who underwent curative resection, the disease stage was upgraded in 10 patients by genetic diagnosis (from Stage IA to Stage IB in 5 patients, from Stage IB to Stage IIIA in 2 patients, from Stage IB to Stage IV in 1 patient, from Stage IB to Stage II in 1 patient, and from Stage II to Stage IIIB in 1 patient). In the latter 10 patients, immunohistochemistry identified LN micrometastases in 4 patients. Two patients with micrometastasis by genetic diagnosis had recurrent disease within 1 year.


CONCLUSIONS
The current results indicate that the multiple-marker RT-PCR assay is a useful tool for the detection of micrometastases in regional LNs in patients with gastric carcinoma and may improve the staging system of gastric carcinoma for these patients.
Okada
Y
Y
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan.
Fujiwara
Y
Y
Yamamoto
H
H
Sugita
Y
Y
Yasuda
T
T
Doki
Y
Y
Tamura
S
S
Yano
M
M
Shiozaki
H
H
Matsuura
N
N
Monden
M
M
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism; D053554:Keratin-20; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery
D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; D053554:Keratin-20; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins