Aims: To determine the association of micro-metastatic matrix metalloproteinase-2 (MMP-2) expression, the absolute lymphocyte count (ALC)) and outcome in stage II colon cancer.
Materials and methods: A single centre, prospective observational study, one month post-surgery blood for ALC, circulating tumour cell (CTC) detection and a bone marrow biopsy for micro-metastasis detection were obtained. CTCs were detected using differential gel centrifugation and immunocytochemistry with anti-CEA and anti-MMP-2, the bone marrow biopsy for the detection of micro-metastasis was processed as for CTCs . At each follow-up ALC and CTC counts were determined. Bone marrow sampling was repeated if the ALC decreased by >10%, at relapse or at the end of the study period. Three MRD subgroups were defined, Group I MRD negative, Group II only positive for micro-metastasis and Group III in which CTCs were detected.
Results: One hundred and eighty one patients participated; 105 (58%) patients formed Group 1, 36 (20%) formed Group II and 40 (22%) formed Group III for a median follow-up of 4 years . Of Group I 3/105 (3%), Group II 16/36 (44%) and Group III 34/40 (84%) patients relapsed. The ALC was significantly higher in Groups I and II, the expression of MMP-2 and MMP-2 score in Group II was significantly lower than in Group III patients. A low ALC was associated with a higher expression of MMP-2 in the micro-metastasis and presence of CTCs.
Conclusions: Patients with stable ALCs did not relapse; decreasing ALCs were associated with increasing MMP-2 scores, the appearance of CTCs and relapse.
Keywords: Colon cancer; circulating tumour cells; immune funcion; lymphocytopenia; micro-metastasis.