Abstract
50 Background: ALCAM (Activated Leukocyte Cell Adhesion Molecule) is thought to be involved in tumor cell adhesion, migration and metastasis. The ectodomain responsible for adhesion is proteolytically shed. Elevated shedding of ALCAM ectodomain is associated with malignant progression. Considering the proximity of urogentical cancer to both urinary secretions and hematogenous circulation we investigated if ALCAM shed into urine and/or blood could act as a prognostic or diagnostic marker of disease and patient outcome. Methods: Shed ALCAM in serum and urine was measured by ELISA while ALCAM shedding in tissues was detected with a unique immunohistochemical approach. ALCAM shedding was correlated with patient parameters including tumor stage, metastasis, recurrence, overall and disease-specific survival. Results: ALCAM shedding was compared across tissue and fluids from normal age-matched healthy adults, non-urological neoplasia, and non-cancer patients. Elevated ALCAM shedding was readily detected in fluids and tissue from patients with urogenital cancers. However, only the detection of shedding in tissue and urine correlated significantly with disease progression and patient outcome. Specifically, shed ALCAM detected in urine collected from bladder cancer patients undergoing cystectomy (Vanderbilt 2000-2010) correlated strongly with patient outcome. Urine ALCAM correlates positively with invasiveness (80%), and is predictive of recurrence as well as survival (HR=10.2 and 2.9). Urinary ALCAM ROC curves show the optimal sensitivity and specificity of predicting recurrence (90 and 68%) and survival (62 and 83%). Conclusions: We show for the first time that cleaved ALCAM is detectable in the urine and that urinary ALCAM is a novel biomarker in urogenital cancers. ALCAM shedding is marker of cancer progression and patient outcome with high specificity and accuracy. Evaluating levels of shed ALCAM in urine offers a unique and effective method to diagnose, assess, and stratify patients with urogenital cancers. We find this correlation particularly exciting because ALCAM is functionally involved in cancer progression and therefore reports on cellular behavior rather than mere presence of neoplastic disease.
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