title: Clinical significance of cell proliferation, microvessel density, and CD44 adhesion molecule expression in renal cell carcinoma.
abstract: Renal cell carcinoma (RCC) is known to have a wide variation in clinical outcome despite the use of conventional prognostic factors, such as staging or grading. A better knowledge of the biologic aggressiveness of RCC could facilitate the selection of patients at high risk of tumor progression. The aim of this study was to determine if use of measurements of vascular density, cell proliferation, and cell adhesion could better predict the biologic behavior of RCC. We immunohistochemically analyzed CD34, Ki-67, and CD44H expression on formalin-fixed, paraffin-embedded tissues from 73 RCCs for quantifying microvessel density (MVD), Ki-67 labeling index (LI), and CD44H LI, respectively. Univariate cancer-specific survival analysis showed that tumor stage (P < .01), tumor size (P < .001), nuclear grade (P < .01), metastasis (P < .001), MVD (P < .03), Ki-67 LI (P < .001), and CD44H LI (P < .0001) were predictors of tumor-related death. There was a statistical correlation between CD44H LI and both Ki-67 LI (r' = .3) and MVD (r' = -44). Ki-67 LI (P < .04) and CD44H LI (P < .02), as well as metastasis (P < .008), emerged as independent predictors of cancer-specific survival in multivariate analysis in patients with metastases (P < .04 and P < .02, respectively) and in patients without metastases (P < .006 and P < .00001, respectively). Our study suggests that vascular density, cell proliferation, and cell adhesion represent a complex tumor-host interaction that may favor progression of RCC. Cell proliferation and CD44H expression appear to be powerful markers to identify patients with an adverse prognosis.
authors.affiliation: Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: N
authors.initials: N
authors.lastname: Rioux-Leclercq
authors.forename: J I
authors.initials: JI
authors.lastname: Epstein
authors.forename: J Y
authors.initials: JY
authors.lastname: Bansard
authors.forename: B
authors.initials: B
authors.lastname: Turlin
authors.forename: J J
authors.initials: JJ
authors.lastname: Patard
authors.forename: A
authors.initials: A
authors.lastname: Manunta
authors.forename: T
authors.initials: T
authors.lastname: Chan
authors.forename: M P
authors.initials: MP
authors.lastname: Ramee
authors.forename: B
authors.initials: B
authors.lastname: Lobel
authors.forename: J P
authors.initials: JP
authors.lastname: Moulinoux
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000276:immunology / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis; D002196:Capillaries / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division; D018450:Disease Progression; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000276:immunology / Q000378:metabolism; D007680:Kidney Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D019394:Ki-67 Antigen