CEACAM1 expression in cutaneous malignant melanoma predicts the development of metastatic disease.
OBJECTIVE
The cell adhesion molecule CEACAM1 is involved in intercellular adhesion and subsequent signal transduction events in a number of epithelia. CEACAM1 downregulation has been demonstrated in colorectal and prostate carcinomas. This study sought to analyze whether its expression in malignant melanoma is associated with metastasis.


METHODS
CEACAM1 expression was immunohistochemically evaluated in 100 primary cutaneous malignant melanomas and correlated with metastasis in a 10-year follow-up. Furthermore, CEACAM1 expression was analyzed in metastatic lesions (11 distant metastases and six sentinel lymph node metastases). Univariate Kaplan-Meier analysis and multivariate Cox proportional hazard regression analysis adjusted for standard prognostic indicators were performed to assess the prognostic relevance of CEACAM1 expression.


RESULTS
A total of 28 of 40 patients with CEACAM1-positive primary melanomas developed metastatic disease, compared with only six of 60 patients with CEACAM1-negative melanomas. Often, the strongest CEACAM1 expression was observed at the invading front. In addition, CEACAM1 expression was preserved in the metastatic lesions. Kaplan-Meier analysis revealed a highly significant association between CEACAM1 expression and metastasis (P <.0001); multivariate Cox regression analysis, including CEACAM1 expression status adjusted for tumor thickness, presence of ulceration, and mitotic rate, confirmed that CEACAM1 is an independent factor for the risk of metastasis and demonstrated that the predictive value of CEACAM1 expression is superior to that of tumor thickness.


CONCLUSIONS
Expression of the cell adhesion molecule CEACAM1 in the primary tumors in melanoma patients is associated with the subsequent development of metastatic disease. This raises the possibility of a functional role for this cell adhesion molecule in the metastatic spread it indicates.
Thies
Anka
A
Institute for Anatomy, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. thies@uke.uni-hamburg.de
Moll
Ingrid
I
Berger
Jürgen
J
Wagener
Christoph
C
Brümmer
Jens
J
Schulze
Hans-Joachim
HJ
Brunner
Georg
G
Schumacher
Udo
U
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018450:Disease Progression; D018572:Disease-Free Survival; D000939:Epitopes; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D008940:Mitotic Index; D011379:Prognosis; D011975:Receptors, Mitogen; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014456:Ulcer / Q000473:pathology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D014408:Biomarkers, Tumor; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D000939:Epitopes; D011975:Receptors, Mitogen