L1CAM expression identifies different colorectal tumor subgroups

Neural cell adhesion molecule L1 (L1CAM) is a stem cell marker belonging to the immunoglobulin superfamily of cell adhesion molecules (IgCAMs). L1CAM shows multiple functions, depending on its homophilic or heterophilic interactions with other L1CAM molecules or with cell-matrix components. Previous studies have shown that L1CAM is aberrantly activated in colon cancer development and progression, being associated with metastasis. The present study was aimed to assess, using immunohistochemistry, the expression pattern of L1CAM in colorectal cancer (CRC), in order to correlate L1CAM expression with the aggressivity of tumor cells. To this end, formalin-fixed paraffin-embedded tissue samples from 51 patients affected by CRC, ranging in age from 38 to 88 years, 21 females and 30 males, were analyzed. The most important finding emerging from our work is the marked interindividual variability in L1CAM immunoreactivity in CRC, with 31 out of 51 (61%) cases expressing L1CAM. In positive cases, the expression of L1CAM in tumor cells ranged from mild immunostaining in 22 cases (score 1), to moderate reactivity in 6 (score 2) to strong and diffuse expression in 3 tumors (score 3). This is a new finding regarding L1CAM expression in CRC, which evidences that in a large cohort (39%) of CRC, tumor cells are not immunoreactive for this cell adhesion molecule. In the vast majority (21 out of 30) of tumors with budding margins and morphological features of epithelial-mesenchymal transition (EMT), L1CAM was focally expressed in 14/21 cases, and 3 out of 21 cases showed high L1CAM immunoreactivity. These properties of L1CAM suggest a major role for L1CAM in tumor cell migration in CRC and make it a potentially useful new marker for cancer progression and a candidate for anti-cancer therapy.