Abstract 1734: MMP-2 as a putative biomarker in body fluid of gastric cancer
Authors: Noh Sewon , Jung Jae-Joon , Jung Minkyu , Park Jun Yong , Kim Tae Soo , Jeung Hei-Chul , Chung Hyun Cheol , Rha Sun Young 
Published: February 2011

Abstract
Carcinoembryonic antigen (CEA) and fluid cytology are widely used in patients with gastrointestinal malignancies for evaluating tumor status, but its sensitivity is low and unsatisfactory. In this study, we evaluated the possibility of MMPs, known to promote cancer progression through increasing cancer cell growth, migration, invasion, metastasis and angiogenesis, as a novel biomarker in the body fluid of advanced gastric cancer. Total 135 body fluids (105 ascites, and 24 pleural fluids) from metastatic or relapsed gastric cancer patients diagnosed with peritoneal carcinomatosis at Severance Hospital, Yonsei University from 2000 to 2009 were collected. To determine the cut-off expression level of MMPs, we performed zymography and ELISA using the conditioned media of HT-1080 at various protein concentrations. Ascitic CEA (aCEA) and pleural CEA (pCEA) was measured by EIA. MMP-2 and MMP-9 levels in patient samples were determined with ELISA. Finally, we compared the expression of MMPs with clinical parameters such as fluid CEA, cytology, and survival. Comparing MMPs activity and expression in HT-1080, positive levels of MMP-2 and MMP-9 were 8.59ng/mL and 0.14ng/mL, respectively. Out of 105 ascitic fluids, MMP-2 had a positivity of 93.7%, MMP-9 34.2%, and aCEA 82.9%. Ascitic fluid cytology of 95 patients showed postitive rate of 55.9%. Combining aCEA and MMP biomarkers, the positivity improved; the positivity of MMP-2 and aCEA was 99.1%, while MMP-9 and aCEA was 86.5%. Interestingly, positivity of MMP-2 in aCEA negative patients was 94.7% and 21.1% in MMP-9. To evaluate the role of MMPs as a prognostic marker, the duration of survival was analyzed from the date when ascites was detected until death. The overall median survival in all patients was 62 days. Comparing survival with MMPs expression level, we found a negative correlation between MMP-2 and survival. We observed that patients with a higher MMP-2 expression, ≥ 22.6ng/mL which showed significant MMP-2 activation in zymography, had a shorter survival with a median of 15 days, while lower expression group had a median of 35 days, P &lt; 0.01. In 24 pleural samples, MMP-2 had a positivity of 66.7%, MMP-9 45.8%, pCEA 70.5%, and cytology was 66.7% (n=18). When we combined these markers, MMP-2 and pCEA together increased the positivity to 91.7%, MMP-9 and pCEA 79.2%, MMP-2, MMP-9, and pCEA 91.7%. In conclusion adding MMPs, especially MMP-2, to fluid CEA increased the positivity allowing us to evaluate clinical status more accurately. Also, higher MMP-2 expression showed poor prognosis in advanced gastric cancer with ascites, suggesting the possibility of MMP-2 as a prognostic marker. With further development, MMPs expression in body fluid can be used to detect residual micrometastasis or predict recurrence in peritoneal washing fluid or pelvic fluid.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1734.