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Introduction: Placental-Cadherin, type 1 (CDH3) is a cell adhesion molecule that plays a role in cellular localization and tissue integrity. Because CDH3 is highly expressed by the placenta (PLC) it holds promise as a cancer testis antigen and, possibly, a vaccine target. Its expression profile in normal tissues has not been well studied, to date. Up-regulation of CDH3 expression has been reported in esophageal, pancreatic, bladder, prostate, melanoma, and breast cancer; expression levels in colorectal cancer (CRC) remain poorly characterized. This study’s aims were: 1) to evaluate CDH3 expression in CRC tumors and other tissues as well as to assess preoperative plasma CDH3 levels and 2) to determine if CDH3 holds promise as a vaccine target.
Methods: An IRB approved plasma and tumor bank was utilized. CRC patients (pts) for whom tumor and normal colon tissue samples were available were enrolled. Demographic and pathologic data were collected prospectively. Tumor samples were OCT embedded and stored at -80C°. Total purified RNA was isolated from tissue samples and cDNA synthesized. CDH3 expression was analyzed by quantitative PCR (QPCR) using the SYBR Green platform. Tumor expressions levels were determined and compared to expression levels in normal colonic tissue and PLC. CDH3 expression in other normal organs was also assessed. Tumors with expression levels 0.1% or more than the PLC result were considered positive. Plasma CDH3 levels were determined via ELISA in pts for whom PreOp blood samples were available. Plasma CDH3 levels and tumor QPCR levels were correlated (P<0.05). Colon and rectal tumor expression levels were also compared (p<0.05).
Results: A total of 77 paired CRC and normal colon specimens (36 M/ 41 F, age 67.3±14.5) were assessed (82% colon, 18% rectal; Cancer Stage 2, 44; Stage 3, 33). All tumors (100%) had CDH3 expression levels over 0.1% of the PLC level and, also, a tumor to normal colon ratio greater than 1.Expression ratios in 25 tumors were above 100 and in 19 tumors were in the 50-100 range. CDH3 expression was noted in 8/20 normal organ tissues. There was a positive correlation between tumor CDH3 QPCR and PreOp CDH3 blood levels (n=57, P= 0.038). Expression levels were significantly higher in rectal vs. colon tumors (p=0.019).
Conclusion: All tumors over expressed CDH3 as judged by RT-PCR when compared to normal colon tissue; tumor expression was also greater than 0.1% of PLC expression levels. Unfortunately, CDH3 was expressed by other normal organs, thus, it is not a promising vaccine target or a cancer testis antigen. Of note, appreciable plasma CDH3 levels were noted and the correlation between plasma and tumor CDH3 levels suggests CDH3 may have value as a prognostic marker. A larger study is needed to determine if plasma and/or tumor expression levels correlate with T, N, or final tumor stage.