Sensitivity to CPT-11 and platinum derivatives of stage II/III node-positive gastric cancer with occult neoplastic cells in lymph node sinuses

Abstract

In this study, immunohistochemistry was used to detect Topo-1 and Bax/ERCC-1 expression in patients who had lymph node metastasis of stage II/III gastric cancer with occult neoplastic cells (ONCs) in their lymph node sinuses. In addition, tumor sensitivity was compared between CPT-11 and platinum agents. In the recurrence group (RG) (n=28), immunohistochemistry revealed high Topo-1 expression in 3 patients (10.7%) and low expression in 25 patients (89.3%), while there was high expression in 1 patient (11.1%) and low expression in 8 patients (88.9%) from the non-recurrence group (N-RG) (n=9) (Not significant; N.S.). Immunostaining showed high Bax/low ERCC-1 expression in 11 patients (39.3%) from the RG and other patterns of expression in 17 patients (60.7%), while high Bax/low ERCC-1 expression was observed in 3 patients (33.3%) from the N-RG and other patterns were noted in 6 patients (66.7%) (N.S.). There was a significant difference between the rate of high-Bax/low-ERCC-1 expression and high Topo-1 expression in the RG (p=0.0136). These results suggest that platinum derivatives such as CDDP are more effective than CPT-11 in both RG and N-RG of stage II/III gastric cancer with ONCs.

Occult neoplastic cells in lymph node sinuses and recurrence/metastasis of stage II/III gastric cancer

“…In patients who have <10 floating cells, ONC(−), these cells are assumed to be eradicated by the host immune system and are unlikely to cause recurrence or metastasis, whereas in those with ≥10 floating cells, ONC(+), certain cells may not be eliminated by the immune system and may proliferate to form micrometastases. Conventionally, tumors that show budding at the leading edge are thought to have a worse prognosis, but certain stage II/III gastric cancer patients without lymph node metastases show a relatively good prognosis ( 8 – 13 ). In the present study, ONC(+) stage II/III gastric cancer without lymph node metastasis was infrequent, accounting for 17.8% of cases (8/45).…”

“…Recurrence, such as peritoneal dissemination, lymph node metastasis, or distant metastasis in patients with lymph node metastasis who undergo curative resection, is presumed to occur when cancer cells that enter the circulation during the perioperative period escape the immune system, enter the microcirculation of target organs and tissues, and find an appropriate microenvironment for growth and proliferation ( 5 – 7 ). Various studies have investigated the close correlation between tumor recurrence/metastasis and the detection of occult neoplastic cells (ONCs) that are positive for cytokeratin on immunohistochemical staining in the sinuses of lymph nodes distant from the primary tumor ( 8 – 13 ). Among patients showing recurrence of stage II/Dukes’ B colorectal cancer without lymph node metastasis, ~20–30% have ONCs.…”