Cytoplasmic CD24 Expression in Colorectal Cancer Independently Correlates with Shortened Patient Survival

Abstract

Purpose: CD24 is a cell adhesion molecule that has been implicated in metastatic tumor progression of various solid tumors. We aimed to clarify the expression patterns of CD24 in colorectal cancer and to correlate these to clinicopathologic variables including patient survival. Experimental Design: 147 colorectal carcinomas and two colon carcinoma cell lines were immunostained for CD24. Cytoplasmic and membranous immunoreactivity were semiquantitatively scored. Fisher's exact test, m 2 test for trends, Kaplan-Meier analysis, and Cox's regression were applied. Results: The cell line CX-2 showed only a minimal membranous CD24 immunoreactivity, in contrast to HT29, which stained strongly in the cytoplasm. In colorectal cancer, 68.7% of the tumors showed membranous CD24 staining, whereas 84.4% showed cytoplasmic staining. In 10% of cases, an exceptionally strong cytoplasmic CD24 expression was observed. The latter significantly correlated to higher tumor stages (Dukes and pT), nodal or systemic metastasis, and higher tumor grade. In survival analysis, strong cytoplasmic CD24 expression correlated significantly (Cox's regression: P = 0.012, relative risk = 3.7) to shortened patient survival in the group of cases without distant metastases. Conclusions: CD24 is commonly up-regulated in colorectal cancer and is a new independent prognostic marker which corroborates the importance of CD24 in tumor progression of this disease.Colorectal cancer is the third most common cause of death from cancer in both sexes in the western world and its high incidence has been stable in the last 20 years (1). Although this disease is surgically curable in early stages, the tumor frequently does not become symptomatic before the metastatic stage, which is associated with high mortality. Therefore, increasing efforts are being made to develop more effective screening and prevention strategies for colorectal cancer and to enhance our capabilities to predict the clinical outcome. Currently, the most important conventional prognostic factors for patient survival are histologic tumor grade and tumor stage at time of diagnosis [pathologic tumornode-metastasis (Unio Internationale Contra Cancrum), Astler-Coller or Dukes], including depth of tumor invasion, involvement of regional lymph nodes, and metastatic spread to distant organs. In addition to these clinicopathologic variables, molecular markers are being evaluated and established for a wide variety of tumors including colon cancer (2). These new markers are being examined for their diagnostic and prognostic effect or even therapeutic implications. In previous works, we have described CD24 as a new prognostic marker in solid tumors (3 -6). Recently, CD24 has been shown to be a prognostic marker in gastric adenocarcinoma (7). CD24 is a small, heavily glycosylated, mucin-like cell surface protein (8 -10). It is expressed in various developing cells including pre-B-cells, keratinocytes, and renal tubulus epithelium, and also in a large variety of malignancies (for a comprehensive revie...

Immunohistochemical Expressionof S100a4 and Cd24 in Colorectal Adenoma and Carcinoma.

“…In the present study,CD24 was predominantly membranous and cytoplasmicinCRC.The findings of Tanakaet al (24) and Weichertet al (25) were consistent with our results.Some researchers focused on the alteration of CD 24 immunolocalization from membranous to cytoplasmic.Choi et al (29) investigated a large sample of ovarian tumors and linked cytoplasmic CD24 immunoreactivity to microinvasion and that the shift from apical membranous staining in normal cells to the cytoplasmic CD24 localization in carcinoma reflects the transition of epithelial cells to a more invasive phenotype which is well-known as epithelial-mesenchymal transition of tumor cells.…”

“…The present results showed that enhanced CD24 expression in CRC was significantly correlated with aggressive clinicopathological features.A significant increase in CD24 expression was detected with higher tumor stage, nodal metastasis and LVSI.Weichert et al (25) reported that cytoplasmic CD24 immunoreactivity was significantly associated with higher tumor stages (Dukes and pT), nodal or systemic metastasis, tumor grade and poor survival.Choi et al (26) reported that CD24 cytoplasmic expression was positively correlated with higher tumor grade, advanced stage and large tumor size.Choi et al (27) observed a significant association between CD24 overexpression and tumor grade in CRC only, but they have not seen any positive correlation between CD24 expression and nodal status and patient survival.…”

The Prognostic Role of Cancer Stem Cell Markers for Long-term Outcome After Resection of Colonic Liver Metastases

“…CD44 expression is found to predict a worsened OS (13), as is CD24 (14). However, another group found no relation between the expression of any of these markers and survival after colon cancer treatment, whilst they did conclude CD133 and CD24 to be correlated with invasiveness and differentiation (28).…”

“…CD24 is a heavily glycosylated cell surface protein, thought to have various functions in proliferation and cell adhesion (12). In colorectal cancer patients, CD44 and CD24 have been associated with decreased OS (13,14), whilst a metaanalysis showed that CD133 is correlated with a worsened OS and DFS (15). Studies regarding the expression of these markers in colonic liver metastases and its influence on survival after hepatectomy are sparse (16)(17)(18).…”

Immunological and Clinical Impact of Cancer Stem Cells in Vulvar Cancer: Role of CD133/CD24/ABCG2-Expressing Cells

“…CD24 is a glycoprotein preferentially expressed by B-lymphocytes, that positively regulates the proliferation of activated T-cells, and it is also described in the central nervous system. Several studies conducted on colorectal cancer demonstrated that this molecule is associated with a poor prognosis and more aggressive phenotype of tumour cells (11). ABCG2 causes decreased drug concentration within the cells by pumping chemotherapeutic drugs out of the cell (12).…”