ALCAM (CD166) Expression as Novel Prognostic Biomarker for Pancreatic Neuroendocrine Tumor Patients

Tachezy, Michael; Zander, Hilke; Marx, Andreas; Gebauer, Florian; Rawnaq, Tamina; Kaifi, Jussuf T.; Sauter, Guido; Izbicki, Jakob R.; Bockhorn, Maximilian

doi:10.1016/j.jss.2011.06.002

Cited by 22 publications

(14 citation statements)

References 34 publications

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“…In contrast to these results, the immunohistochemical staining protocol in the present study revealed a predominantly membranous expression of the adhesion molecule ALCAM (Figure 1) [27], [30], [31], [32]. Cytoplasmatic staining intensity was related to the intensity of the membranous staining and did not occur in the absence of membranous staining.…”

Section: Discussioncontrasting

confidence: 99%

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ALCAM (CD166) Expression and Serum Levels in Pancreatic Cancer

et al. 2012

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BackgroundThis study was conducted to evaluate the expression of the activated leukocyte cell adhesion molecule (ALCAM) in pancreatic cancer (PAC) and to determine whether or not the ectodomain shedding of ALCAM (s-ALCAM) could serve as a biomarker in the peripheral blood of PAC patients.Material and MethodsTissue specimens and blood sera of patients with PAC (n = 264 and n = 116, respectively) and the sera of 115 patients with chronic pancreatitis (CP) were analyzed via ALCAM immunohistochemistry and s-ALCAM ELISA tests. Results were correlated with clinical, histopathological, and patient survival data (Chi-square test, Kaplan-Meier analysis, log-rank test, respectively).ResultsALCAM was expressed in the majority of PAC lesions. Immunohistochemistry and serum ELISA tests revealed no association between ALCAM expression in primary tumors or s-ALCAM and clinical or histopathological data. Neither ALCAM nor s-ALCAM showed a significant impact regarding overall survival (p = 0.261 and p = 0.660, respectively). S-ALCAM serum levels were significantly elevated compared to the sera of CP patients (p<0.001). The sensitivity of s-ALCAM in detecting PAC was 58.6% at a specificity of 73.9% (AUC = 0.69).ConclusionsALCAM is expressed in the majority of PAC lesions, but statistical analysis revealed no association with clinical or pathological data. Although significantly elevated in patients with PAC, the sensitivity and specificity of the s-ALCAM serum quantification test was low. Therefore, its potential as a novel diagnostic marker for PAC remains elusive and further investigations are required.

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Section: Discussioncontrasting

confidence: 99%

“…Its expression is associated with diverse outcomes in different tumors [17], [18], [19], [20], [25], [26], [27], [28], [29], [30], [31], [32]. Furthermore, the extracellular domain of ALCAM (s-ALCAM) is shed by metalloproteases (for example, ADAM 17), functions as an active messenger and interacts with surrounding tissues [33].…”

Section: Introductionmentioning

confidence: 99%

ALCAM (CD166) Expression and Serum Levels in Pancreatic Cancer

et al. 2012

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“…Tachezy et al [11] found that CD166 was predominantly expressed at the cell membrane and that cytoplasmic staining intensity was related to the intensity of membranous staining and did not occur in the absence of membranous staining; thus, only membranous staining was considered in their study. The other three studies in this meta-analysis that focused on membranous staining including colorectal and pancreatic cancer, all concluded that high CD166 expression is a positive marker for good prognosis [10], [14], [36]. In contrast, the three studies in our analysis that analyze both membrane and cytoplasmic staining intensity propose that CD166 high expression contributes to poor clinical outcome [8], [30], [31].…”

Section: Discussionmentioning

confidence: 61%

Prognostic Value of CD166 Expression in Cancers of the Digestive System: A Systematic Review and Meta-Analysis

et al. 2013

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ObjectiveMany studies have reported the prognostic predictive value of CD166 as a cancer stem cell marker in cancers of the digestive system; however, its predictive value remains controversial. Here, we investigate the correlation between CD166 positivity in digestive system cancers and clinicopathological features using meta-analysis.MethodsA comprehensive search in PubMed and ISI Web of Science through March of 2013 was performed. Only articles containing CD166 antigen immunohistochemical staining in cancers of the digestive system were included,including pancreatic cancer, esophageal cancer, gastric cancer and colorectal cancer. Data comparing 3- and 5-year overall survival along with other clinicopathological features were collected.ResultsNine studies with 2553 patients who met the inclusion criteria were included for the analysis. The median rate of CD166 immunohistochemical staining expression was 56% (25.4%–76.3%). In colorectal cancer specifically, the results of a fixed-effects model indicated that CD166-positive expression was an independent marker associated with a smaller tumor burden (T category; RR = 0.93, 95%, CI: 0.88–0.98) but worse spread to nearby lymph nodes (N category; RR = 1.17, 95% CI: 1.05–1.30). The 5-year overall survival rate was showed relationship with cytoplasmic positive staining of CD166 (RR = 1.47 95% 1.21–1.79), but no significant association was found in the pool or any other stratified analysis with 3- or 5- year overall survival rate.ConclusionBased on the published studies, different cellular location of CD166 has distinct prognostic value and cytoplasmic positive expression is associated with worse prognosis outcome. Besides, our results also find CD166 expression indicate advanced T category and N-positive status in colorectal cancer specifically.

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“…Indeed, ALCAM protein levels frequently fail to correlate with gene transcription [33]. In addition, histological detection of ALCAM has been shown to correlate with disease progression and patient outcome in several non-urothelial cancers [26, 27, 33–38]. …”

Section: Resultsmentioning

confidence: 99%

Shed urinary ALCAM is an independent prognostic biomarker of three-year overall survival after cystectomy in patients with bladder cancer

Egloff

Loomans

et al. 2016

Oncotarget

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Proteins involved in tumor cell migration can potentially serve as markers of invasive disease. Activated Leukocyte Cell Adhesion Molecule (ALCAM) promotes adhesion, while shedding of its extracellular domain is associated with migration. We hypothesized that shed ALCAM in biofluids could be predictive of progressive disease. ALCAM expression in tumor (n = 198) and shedding in biofluids (n = 120) were measured in two separate VUMC bladder cancer cystectomy cohorts by immunofluorescence and enzyme-linked immunosorbent assay, respectively. The primary outcome measure was accuracy of predicting 3-year overall survival (OS) with shed ALCAM compared to standard clinical indicators alone, assessed by multivariable Cox regression and concordance-indices. Validation was performed by internal bootstrap, a cohort from a second institution (n = 64), and treatment of missing data with multiple-imputation. While ALCAM mRNA expression was unchanged, histological detection of ALCAM decreased with increasing stage (P = 0.004). Importantly, urine ALCAM was elevated 17.0-fold (P < 0.0001) above non-cancer controls, correlated positively with tumor stage (P = 0.018), was an independent predictor of OS after adjusting for age, tumor stage, lymph-node status, and hematuria (HR, 1.46; 95% CI, 1.03–2.06; P = 0.002), and improved prediction of OS by 3.3% (concordance-index, 78.5% vs. 75.2%). Urine ALCAM remained an independent predictor of OS after accounting for treatment with Bacillus Calmette-Guerin, carcinoma in situ, lymph-node dissection, lymphovascular invasion, urine creatinine, and adjuvant chemotherapy (HR, 1.10; 95% CI, 1.02–1.19; P = 0.011). In conclusion, shed ALCAM may be a novel prognostic biomarker in bladder cancer, although prospective validation studies are warranted. These findings demonstrate that markers reporting on cell motility can act as prognostic indicators.

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ALCAM (CD166) Expression as Novel Prognostic Biomarker for Pancreatic Neuroendocrine Tumor Patients

Cited by 22 publications

References 34 publications

ALCAM (CD166) Expression and Serum Levels in Pancreatic Cancer

ALCAM (CD166) Expression and Serum Levels in Pancreatic Cancer

Prognostic Value of CD166 Expression in Cancers of the Digestive System: A Systematic Review and Meta-Analysis

Shed urinary ALCAM is an independent prognostic biomarker of three-year overall survival after cystectomy in patients with bladder cancer

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