title: Prognostic significance of ALCAM (CD166/MEMD) expression in cutaneous melanoma patients.
abstract: BACKGROUND
  ALCAM (activated leukocyte cell adhesion molecule, CD166, MEMD) is a transmembrane protein of immunoglobulin superfamily (Ig-SF) and plays an important role in human malignant melanoma progression and formation of locoregional and distant metastases. The study using melanoma cell lines showed that overexpression of ALCAM is directly related with the increase of cytoaggregation and the ability to form cell nests. The aim of the study was to assess the expression and intracellular localization of ALCAM in primary skin melanomas and metastatic lesions from regional lymph nodes. Also, prognostic significance of ALCAM expression in primary tumor cells and metastatic lesion cells was evaluated in the context of 5-year observation.
  
  
  METHODS
  Formalin-fixed paraffin-embedded tissue specimens from 104 primary cutaneous melanomas and 16 regional lymph nodes metastases were studied for the expression of ALCAM measured by immunohistochemistry.
  
  
  RESULTS
  We demonstrate that high ALCAM expression in primary melanoma cells (IRS ≥8) is strongly correlated with unfavorable prognosis as compared with patients with lower ALCAM immunoreactivity in tumor compartment as regards cancer specific overall survival (CSOS) (P = 0.001) and disease free survival (DFS) (P < 0.001). Additionally lower ALCAM immunoreactivity in nodal metastatic foci was significantly statistically correlated with deeper melanoma invasion in the primary tumor according to Clark scale (P = 0.032). It was also found that decreased ALCAM expression (IRS <8) in nodal metastases shows a trend related with a correlation with shorter cancer specific overall survival (P = 0.083). Statistically significant correlations were also demonstrated between the presence of ulceration and decreased intensity of lymphocytic inflammatory infiltration and a high percentage of ALCAM-positive cells (P = 0.035, P = 0.01, respectively).
  
  
  CONCLUSIONS
  High ALCAM expression in melanoma cells of the primary tumor can be used as a marker of negative outcome and may indicate a more invasive phenotype of cancer cells, which would require a more intensive therapeutic strategy. Low expression of ALCAM in regional lymph node metastases is a feature associated with unfavorable prognosis in patients with cutaneous melanoma. Our study is the first one to evaluate the effect of increased ALCAM expression on long-term survival in melanoma patients.
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland. piotrdonizy@wp.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Donizy
authors.affiliation: Lower Silesian Oncology Centre, pl. Hirszfelda 12, 53-413, Wroclaw, Poland. zietekm@op.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Zietek
authors.affiliation: Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland. ahalon2@gmail.com.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Halon
authors.affiliation: Department of Statistics, Wroclaw University of Economics, Komandorska 118-120, 53-345, Wroclaw, Poland. marek.leskiewicz@gmail.com.
authors.forename: Marek
authors.initials: M
authors.lastname: Leskiewicz
authors.affiliation: Department of Statistics, Wroclaw University of Economics, Komandorska 118-120, 53-345, Wroclaw, Poland. Cyprian.Kozyra@ue.wroc.pl.
authors.forename: Cyprian
authors.initials: C
authors.lastname: Kozyra
authors.affiliation: Lower Silesian Oncology Centre, pl. Hirszfelda 12, 53-413, Wroclaw, Poland. rafal.matkowski@am.wroc.pl.|Department of Oncology and Division of Surgical Oncology, Wroclaw Medical University, pl. Hirszfelda 12, 53-413, Wroclaw, Poland. rafal.matkowski@am.wroc.pl.
authors.forename: Rafal
authors.initials: R
authors.lastname: Matkowski
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005326:Fetal Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000737:chemistry* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D055815:Young Adult; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule