Original contributionLow activated leukocyte cell adhesion molecule expression is associated with advanced tumor stage and early prostate-specific antigen relapse in prostate cancer☆,☆☆
Introduction
Activated leukocyte cell adhesion molecule (ALCAM; CD166) is a member of the immunoglobulin superfamily. ALCAM is a cell adhesion molecule expressed by epithelial cells in several organs and is involved in embryogenesis, angiogenesis, hematopoiesis [1], and immune response [2]. Alterations in expression of ALCAM have been reported in different malignancies including melanoma [3], bladder cancer [4], breast cancer [5], [6], colorectal cancer [7], [8], esophageal squamous cell cancer [9], pancreatic cancer [10], oral squamous cell cancer [11], ovarian cancer [12], neuroblastoma [13], and prostate cancer [14], [15], [16], [17]. ALCAM expression is increased in some tumors and down-regulated in others. An association between high ALCAM expression and unfavorable prognosis has been shown for colorectal cancer [7], pancreatic cancer [10], esophageal squamous cell cancer [9], and neuroblastoma [13]. In contrast, several studies on breast cancer suggested that reduced ALCAM expression is associated with poor prognosis [5].
ALCAM expression occurs in normal prostate epithelium [16], [17]. The role of ALCAM in prostate cancer is unclear. An increased ALCAM expression in low-grade as compared with high-grade prostate cancer was described in a study analyzing 54 cancers by immunohistochemistry [16] However, the same group found a significant association between high cytoplasmatic ALCAM staining and early biochemical recurrence in a series of 42 patients [17]. In addition to its prognostic role, ALCAM represents a potential future target for therapy. The utility of ALCAM as a drug target structure may be further enhanced by ligand-induced endocytosis [18]. Moreover, in a recently described internalizing single-chain antibody [18], [19], targeting ALCAM has been suggested for potential intracellular delivery of various therapeutic agents to prostate cancer cells.
The aim of our study was to clarify the prevalence and prognostic role of ALCAM expression in prostate cancer by using a preexisting tissue microarray (TMA) including more than 3000 prostate cancers mostly with clinical follow-up data. The data show that ALCAM expression is abundant in prostate cancer and that high-level ALCAM expression is associated with favorable tumor phenotype and good prognosis.
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Patients
Radical prostatectomy specimens were available from 3261 patients, consecutively treated at the Department of Urology, University Medical Center Hamburg-Eppendorf, between 1992 and 2005 (Table 1). Follow-up data were available for 2385 patients, ranging from 1 to 144 months (mean, 34 months). None of the patients received neoadjuvant therapy. Additional (salvage) therapy was initiated in case of a biochemical relapse (BCR). In all patients, prostate-specific antigen (PSA) values were measured
Technical issues
A total of 2390 (73.3%) of tumor samples were interpretable in our TMA analysis. Reasons for noninformative cases (821; 26.7%) included complete lack of tissue samples or absence of unequivocal cancer tissue in the TMA section.
Immunohistochemistry
ALCAM immunostaining always showed strong membrane predominance in our tissues. Although some cytoplasmatic staining was seen, this was always significantly associated with a strong membranous staining (P < .0001). Only 72 of 1392 cytoplasmatic positive cases revealed a
Discussion
The results of this study show that ALCAM is expressed in almost all prostate cancers. Expression differences that were perceivable at bright field immunohistochemistry were only found after marked dilution of the antibody in our protocol development efforts. A dilution series was performed to find experimental conditions that differentiate between low and high ALCAM expressers. Although almost all tumors were ALCAM positive at a dilution of 1:450, the fraction of positive cases reduced to 70%
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ALCAM/CD166: A pleiotropic mediator of cell adhesion, stemness and cancer progression
2021, Cytokine and Growth Factor ReviewsActivated leukocyte cell adhesion molecule (ALCAM/CD166) expression in head and neck squamous cell carcinoma (HNSSC)
2014, Pathology Research and PracticeCitation Excerpt :Previous studies show variable ALCAM expression in malignancies. Increased (membranous and/or cytoplasmic) ALCAM expression was found in several carcinoma entities, including pancreas, colorectal, prostate, ovary, esophagus and oral squamous cell carcinoma and malignant melanoma [5–10]. For example, colorectal cancer and esophageal squamous cell carcinoma showed a significant correlation between ALCAM immunohistochemical staining and tumor stage, lymph node status and clinical stage [6,7].
βIII-tubulin overexpression is an independent predictor of prostate cancer progression tightly linked to ERG fusion status and PTEN deletion
2014, American Journal of PathologyHigh lysophosphatidylcholine acyltransferase 1 expression independently predicts high risk for biochemical recurrence in prostate cancers
2013, Molecular OncologyCitation Excerpt :LPCAT1 staining was evaluated according to the following scoring system: The staining intensity (0, 1+, 2+, and 3+) and the fraction of positive tumor cells were recorded for each tissue spot. A final score was built from these two parameters according to the following established score, as previously described (Grupp et al., 2013; Minner et al., 2011b,c; Muller et al., 2013) Negative scores had absence of LPCAT1 staining, weak scores had staining intensity of 1+ in ≤70% of tumor cells or staining intensity of 2+ in ≤30% of tumor cells; moderate scores had staining intensity of 1+ in ≥70% of tumor cells, staining intensity of 2+ in >30% but in ≤70% of tumor cells or staining intensity of 3+ in ≤30% of tumor cells; strong scores had staining intensity of 2+ in >70% of tumor cells or staining intensity of 3+ in >30% of tumor cells. Statistical calculations were performed with JPM 9 software (SAS Institute Inc., NC, USA).
Sieving through the cancer secretome
2013, Biochimica et Biophysica Acta - Proteins and ProteomicsCitation Excerpt :Although the authors proposed that ALCAM could be a novel biomarker for diagnosis of breast cancer, further studies that integrate mammography with ALCAM may be necessary to validate the clinical potential of ALCAM. Moreover, since the levels of ALCAM have been reported to be regulated in many other cancers [78–83], the specificity of ALCAM for breast cancer as compared to other tumor types should also be addressed in future studies. Likewise in search for serological biomarkers of breast cancer progression, Boersema and colleagues [84] enriched for N-glycosylated peptides from the CM of 11 breast cancer cell lines of various TNM stages using the ‘filter-aided sample preparation’ (FASP) technology.
Activated leukocyte cell adhesion molecule (CD166) - Its prognostic power for colorectal cancer patients
2012, Journal of Surgical ResearchCitation Excerpt :ALCAM plays a role in the development of different tissues during embryogenesis and in adults, and it functions via homotypic and heterotypic interactions between the cells [12–14]. It also is expressed in various malignant lesions, such as melanoma and esophageal, gynecologic, prostate, and pancreatic cancers, and its expression is associated with diverse outcomes in different tumors [12–19]. As with other membrane proteins, ALCAM represents a potential target for therapy, and its utility as a drug target may be further enhanced by ligand-induced endocytosis [20].
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This project was supported by the German Federal Ministry of Education and Science in the framework of the program for medical genome research, Germany (FKZ: 01GS08189).
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There is no conflict of interest to disclose.