Detection of free peritoneal cancer cells in gastric cancer using cancer-specific Newcastle disease virus.
BACKGROUND
Cytologic detection of peritoneal gastric cancer cells by Papanicolaou staining offers important prognostic information but has low sensitivity. We evaluated a novel detection technique using Newcastle disease virus expressing the enhanced green fluorescent protein (NDV-GFP) gene.


METHODS
NDV-GFP was tested on MKN-1 human gastric adenocarcinoma cells plated upon rat hepatocytes to determine tumor-specific infection and GFP expression. Malignant ascites infected with increasing doses of virus was evaluated for NDV-GFP dose determination. Peritoneal lavage samples from 30 patients with gastric adenocarcinoma undergoing staging laparoscopy were evaluated with NDV-GFP.


RESULTS
NDV-GFP can specifically detect one MKN-1 cell among one million benign rat hepatocytes. NDV-GFP at 5 x 10(6) plaque-forming units (PFU) produced optimal GFP expression in malignant ascites. Noncancerous cells were non-GFP expressing. GFP-expressing cells counterstained positive for carcinoembryonic antigen expression, confirming their cancerous origin. Furthermore, in patients with advanced gastric cancer, GFP expression was markedly enhanced over cytology. Of six patients with M1 disease discovered during laparoscopy, only 50% were cytology positive. All six, however, were NDV-GFP positive. Cytology was positive in 9% of patients with T3 disease, 8% with N1 disease, and 50% with N2 disease. In contrast, NDV-GFP was positive in 95% of T3 patients and 100% of patients with N1 or N2 disease.


CONCLUSIONS
NDV-GFP can specifically infect and detect peritoneal gastric cancer cells and offers a more sensitive method compared with conventional cytology. This novel modality may offer enhanced detection of intraperitoneal cancer spread and provide important prognostic information.
Wong
Joyce
J
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Schulman
Allison
A
Kelly
Kaitlyn
K
Zamarin
Dmitriy
D
Palese
Peter
P
Fong
Yuman
Y
D000230:Adenocarcinoma / Q000473:pathology* / Q000556:secondary; D000818:Animals; D001202:Ascitic Fluid / Q000473:pathology*; D002272:Carcinoembryonic Antigen / Q000032:analysis; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000235:genetics; D022781:Hepatocytes; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D009522:Newcastle disease virus / Q000235:genetics*; D010533:Peritoneal Lavage; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000556:secondary*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013274:Stomach Neoplasms / Q000473:pathology*
D002272:Carcinoembryonic Antigen; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins