title: M-CAM expression as marker of poor prognosis in epithelial ovarian cancer.
abstract: Currently available clinico-pathologic criteria provide an imperfect assessment of outcome for patients with advanced epithelial ovarian cancer (EOC). Identification of prognostic factors related to tumor biology might improve this assessment. We investigated the prognostic significance of the melanoma cell adhesion molecule (M-CAM) in EOC. Using the same antibody, M-CAM expression was tested by Western blotting in protein extracts and by immunohistochemestry in tissue microarrays generated from 133 consecutively resected, well characterized EOC samples. Fisher test, Kaplan-Meier method and Cox proportional hazards analysis were used to relate M-CAM expression to clinico-pathological variables and to time to progression (TTP) and overall survival (OS). In vitro biochemical analysis showed a progressively increased M-CAM expression from normal to malignant cells. M-CAM protein, detected immunohistochemically, was significantly associated with advanced tumor stage, serous and undifferentiated histotype, extent of residual disease and p53 accumulation. Presence or absence of M-CAM significantly divided patients according to their TTP (median, 22 vs. 79 months, respectively; log-rank p = 0.001) and OS (median, 42 vs. 131 months, respectively; log-rank p = 0.0003). In the subgroup of advanced stage patients who achieved complete response after front-line treatment, M-CAM expression and absence of residual disease were significantly associated with shorter TTP (p = 0.003, HR 5.25, 95% Cl 1.79-15.41 and p = 0.011, HR 3.77, 95% Cl 1.36-10.49 respectively) at the multivariate level. In the same sub-group of patients, M-CAM expression remained the only parameter significantly associated with OS (p = 0.005, HR 3.35, 95% Cl 1.42-6.88). M-CAM is a marker of early relapse and poorer outcome in EOC. In particular, M-CAM expression identifies a subgroup of front-line therapy-responding patients who undergo dramatic relapses, thus helping to better select patients who might benefit from new/alternative therapeutic modalities.
authors.affiliation: Department of Pathology, S. Chiara Hospital, Trento, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Aldovini
authors.forename: Francesca
authors.initials: F
authors.lastname: Demichelis
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.forename: Dolores
authors.initials: D
authors.lastname: Di Vizio
authors.forename: Enzo
authors.initials: E
authors.lastname: Galligioni
authors.forename: Sonia
authors.initials: S
authors.lastname: Brugnara
authors.forename: Bruna
authors.initials: B
authors.lastname: Zeni
authors.forename: Claudia
authors.initials: C
authors.lastname: Griso
authors.forename: Cristina
authors.initials: C
authors.lastname: Pegoraro
authors.forename: Marina
authors.initials: M
authors.lastname: Zannoni
authors.forename: Manuela
authors.initials: M
authors.lastname: Gariboldi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Balladore
authors.forename: Delia
authors.initials: D
authors.lastname: Mezzanzanica
authors.forename: Silvana
authors.initials: S
authors.lastname: Canevari
authors.forename: Mattia
authors.initials: M
authors.lastname: Barbareschi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D051929:CD146 Antigen / Q000378:metabolism; D002460:Cell Line; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010053:Ovary / Q000378:metabolism; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D051929:CD146 Antigen; C497902:MCAM protein, human