Flow Cytometric Quantification of Intraperitoneal Free Tumor Cells is a Useful Biomarker in Gastric Cancer Patients with Peritoneal Metastasis
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The frequency of intraperitoneal free tumor cells (IPTC) is considered to reflect the severity of peritoneal metastasis (PM). We quantified the relative number of IPTC against leukocytes in peritoneal fluid and evaluated its clinical relevance in gastric cancer (GC) patients, particularly those with PM.
Cells recovered from ascites or peritoneal lavage fluid were immunostained with monoclonal antibodies (mAb) to CD45 and CD326 (EpCAM). Using flow cytometry (FACS), CD326(+) and CD45(+) cells were classified as either tumor cells (T) or leukocytes (L) and the T/L ratio (TLR) was calculated in a total of 506 samples obtained from 300 patients with GC and 33 patients with liver cirrhosis (LC).
Median (M) of the TLR of the initial samples obtained from 199 patients with PM(+) GC was 1.32 % (0–1,868.44 %), which was significantly higher than that in patients with PM(−) GC (M = 0 %, 0–0.35 %; n = 101) or LC (M = 0 %, 0–0.031 %; n = 33). In 104 PM(+) patients who received combination chemotherapy including intraperitoneal paclitaxel, the TLR was repeatedly measured in peritoneal fluid obtained from the port. In these patients, the TLR showed a strong correlation with clinical features as well as cytological findings and carcinoembryonic antigen messenger RNA status. Finally, the median survival time of the 11 patients with initial TLR > 10 % was significantly shorter than that of the 52 patients with TLR < 10 % (271 vs. 627 days; p = 0.0002).
The TLR excellently reflected tumor burden in the peritoneal cavity, and could be a reliable biomarker to determine the outcome, as well as the effectiveness, of chemotherapy in patients with PM(+) GC.
KeywordsGastric Cancer Reverse Transcription Polymerase Chain Reaction Peritoneal Metastasis Ascitic Fluid Peritoneal Fluid
We thank Ms. Chieko Uchikawa, Ikuko Nieda, and Yu Saito for their excellent technical and clerical support. This study was financially supported by the Ministry of Health, Labor and Welfare of Japan. This work was funded by the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Ministry of Health, Labor and Welfare of Japan, and by a Grant-in-aid of the Public Trust Surgery Research Fund, Tokyo, Japan.
Joji Kitayama, Shigenobu Emoto, Hironori Yamaguchi, Hironori Ishigami, Haruna Onoyama, Hiroharu Yamashita, Yasuyuki Seto, Keisuke Matsuzaki, and Toshiaki Watanabe have no financial disclosures.
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