Expression of Lewisa, sialyl Lewis3, Lewisx and sialyl Lewisx antigens: DISCUSSION Part 1
The present study revealed that the expression of Lex or sialyl Lex antigen (a type 2 chain carbohydrate antigen) in colorectal carcinomas is associated with poor prognosis. On the other hand, the expression of Lea or sialyl Lea antigen (a type 1 chain carbohydrate antigen) in colorectal carcinomas was not associated with patient survival.
Expression of Lex and sialyl Lex antigens in solid tumours as prognostic factors in cancer patients: In some solid tumours, incomplete synthesis of cell surface carbohydrates results in increased expression of ABH precursor structures such as Lex and sialyl Lex, and their isomers Lea and sialyl Lea, respectively. Because the syntheses of Lex and sialyl Lex are independent of the patient’s ABH and secretor status, in contrast to ABH isoantigens, they are more suitable for clinical studies. Sialyl Lex and related carbohydrate structures function as adhesion molecules, and theoretically they may be involved in tumour metastasis. It is interesting that their expression in certain tumours is correlated with prognosis.
Sialyl Lex was found in the extracts of most colon carcinomas but not in the extracts of normal colonic mucosa. Sialyl Lex expression is stronger in liver metastatic lesions than in primary colorectal tumours. An immuno-histochemical study demonstrated that metastatic lesions contain a higher percentage of sialyl Lex-positive tumour cells than primary tumours. Ono et al reported that focal dedifferentiation of cancer cells at the invasive front and sialyl Lex antigen expression in colorectal carcinomas are each correlated with a high risk of developing liver metastasis. In addition, it was previously reported that increased sialyl Lex antigen expression in colorectal carcinomas, detected immunohistochemically by monoclonal antibody CSLEX1, was correlated with poor prognosis. Nakamori et al also reported that increased expression of sialyl Lex in colorectal carcinomas is correlated with a poor prognosis.
However, Nakamori et al used monoclonal antibody FH-6 to detect sialyl Lex and found that the specificity of FH-6, which is directed toward the dimeric version of sialyl Lex antigen, and the specificity of CSLEX1 antibody differ slightly. Thus, it has been established that sialyl Lex expression in colorectal tumours is a useful tumour-associated marker that indicates the degree of tumour aggressiveness and subsequent outcome. Take advantage of this opportunity – buy levaquin 750 mg to enjoy lowest prices online.
The relation between Lex antigen expression and tumour behaviour and subsequent outcome in breast, esophageal and lung carcinomas has been reported. However, the relation between Lex antigen expression as shown by immunohistochemistry and patient prognosis among colorectal carcinoma patients has not been reported. Singhal et al reported that the serum Lex antigen level has prognostic value in Dukes C colon cancer patients after surgery and during postoperative follow-up. The present study revealed the prognostic value of Lex antigen expression in colorectal carcinoma.
Lex antigen, which is the precursor of type 2 ABH isoantigens, was initially discovered as a stage-specific embryonic antigen and is considered to be involved in cell differentiation during embryogenesis, and in the growth and differentiation of cells. A previous report showed that Lex antigen is involved in cell-cell recognition at the beginning of cell differentiation. Loss of ABH isoantigens is correlated with tumour progression, metastatic potential and poor prognosis in various tumours. The loss of ABH isoantigens may result in the accumulation of precursor Lex antigen during tumour development. Cancer patients have elevated sialyltransferase activity in both the cancer tissue and the sera. Consequently, the sialylated form of Lex is more prevalent than its nonsialylated form in tumours.
The significance of increased sialyl Le expression in tumours may be related to the presence of receptors for sialyl Lex-carrying ligands on activated endothelial cells. Cytokine-activated endothelial cells express endothelial leukocyte adhesion molecule-1 (ELAM-1) – an adhesion molecule belonging to the selectin family. ELAM-1 recognizes the sialylated form of Lex and related structures. Several studies have shown that tumour cells expressing sialyl Lex adhere to interleukin-activated, cultured endothelial cells. In addition, Tsumatori et al reported that patients with sialyl Lex antigen-positive, nonsmall cell lung cancer who had a high serum E-selectin level had poor prognosis after surgical resection.