RESUMEN
Serum CEA is among the most widely accepted marker for diagnosing and monitoring colorectal cancer [CRC] yet it has many limitations. The objective of the present study was to evaluate the utility of plasma CEA-mRNA as a marker for early detection of micrometastasis and assess its usefulness versus that of serum CEA in CRC patients. This study included 36 patients with CRC who were staged according to Dukes' staging system into stage A [n = 4], B [n = 8] C [n = 14] and stage D [n = 10]. Patients included in Dukes' stages A and B [n = 12] had non-metastatic lesion and were considered as one group [group I] while those having stages C and D [n = 24] had metastatic lesions. Patients with metastatic lesions who weren't receiving chemotherapy were included in one group [group II, n = 20] while those on chemotherapy [5 fluorouracil and leukovorin] were considered as group III [n = 4]. Six patients suffering from benign colorectal disease [ulcerative colitis n = 2, diverticulitis n = 1 and polyps n=3] and six healthy age and gender matched and with normal serum CEA concentration were included in the study and were considered as the control group [group IVa, group IVb respectively]. All CRC patients were subjected to clinical, radiological, endoscopic, histopathological and laboratory assessment. Control subjects were assessed both clinically and laboratory wise. Serum CEA was assayed by chemiluminescent sequential immunometric assay while plasma CEA-mRNA was determined by semi nested reverse transcription RT-PCR. The median and inter-quartile values for serum CEA in groups I, II and III were 2.5 [1.5-3.4], 4.6 [2.8-9.9] and 4.2 [2.9-5.3] ng/mL respectively. As for the control groups, it was 2 [0.9-2.2] ng/mL in group IVa and 3.3 [2.1-4.0] ng/mL in group IVb. When compared to controls, serum CEA was significantly higher only in metastatic patients [group II and III], however, when compared to non-metastatic CRC, serum CEA was significantly higher only in patients not on chemotherapy [group II]. The degree of tumor differentiation had no significant impact on serum CEA concentration. Our results also demonstrated that the percent positivity for CEA-mRNA increase with advancing CRC stage where a highly significant increase was observed in metastatic patients [65%] when compared to non metastatic ones [8.3%]. Our results also showed that CEA- mRNA may be positive in subjects with benign colorectal diseases [8.3%] and that chemotherapy may result in negative results for m-RNA. Again, the degree of differentiation had no impact on percent positivity of CEA- mRNA. Finally, our results showed that serum CEA and percent positivity of CEA- mRNA do not correlate and that the recurrence rate in patients with positive CEA-mRNA is significantly high [70%]. Reverse-trancriptase polymerase chain reaction for CEA-mRNA is a sensitive method for detection of circulating cancer cells in CRC patients. Colorectal cancer patients with postoperative CEA-mRNA positive cells in peripheral blood have less disease free survival than patients who demonstrate absence of these cells. Studies involving a larger group of patients with a longer follow-up period should be done to implement the clinical relevance of this phenomenon. Patients receiving chemotherapy should not be tested for CEA-mRNA during the treatment course. They should be tested repeatedly thereafter at longer time intervals following the last dose of chemotherapy