 |
|
Tumor Vascularity, Proliferation, and Apoptosis in Human Melanoma Micrometastases and Macrometastases
Raymond L. Barnhill, MD;
Michael W. Piepkorn, MD, PhD;
Alistair J. Cochran, MD;
Evelyn Flynn;
Themis Karaoli;
Judah Folkman, MD
Arch Dermatol. 1998;134:991-994.
Background Clinically undetectable or dormant metastases (mircrometastases) probably account for disease recurrence, ie, clinically evident metastases, in patients after disease-free intervals of variable length. Recently developed animal models have shown that dormancy may potentially be explained by the fact that these micrometastases are not vascularized and have comparable rates of cellular proliferation and programmed cell death (apoptosis), enabling them to remain viable indefinitely but not to show progressive growth.
Observations We report for the first time that melanoma micrometastases from humans are similarly not vascularized (mean number of microvessels, 10.2), have significantly lower rates of tumor cell proliferation (mean, 2.4%), and comparable rates of proliferation and apoptosis (means, 2.4% and 0.2%, respectively), compared with melanoma macrometastases, which have significantly greater tumor vascularity (mean number of microvessels, 18.7), higher rates of proliferation (mean, 18%), and higher rates of proliferation relative to apoptosis (means, 18% vs 1.6%). Tumor vascularity was quantified using the lectin Ulex europaeus agglutinin I to identify the number of microvessels per unit area (microscope ocular grid with an area of 7.84 x10-2 mm2 at x400 magnification). Melanoma cell proliferation rate was assessed with the MIB-1 antibody (Ki-67) as the number of positive nuclei per total number of tumor nuclei counted at x400 magnification. Apoptosis was quantified using the method of terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate–biotin nick end labeling. The number of positive nuclei were quantified per total number of tumor nuclei; usually 200 tumor nuclei were counted at x400 magnification.
Conclusion We report, for the first time, that human micrometastases demonstrate attributes, ie, the lack of significant tumor vascularity and low but comparable rates of proliferation and apoptosis, that may explain the dormant state.
From the Dermatopathology Division, Department of Pathology, Brigham and Women's Hospital (Dr Barnhill and Mr Karaoli), and Surgical Research, Children's Hospital (Ms Flynn and Dr Folkman), Harvard Medical School, Boston, Mass; the Departments of Medicine (Dermatology) and Pathology, University of Washington School of Medicine, Seattle (Dr Piepkorn); and the Department of Pathology, University of California at Los Angeles (Dr Cochran). Dr Barnhill is now with the Division of Dermatopathology and Oral Pathology, The Johns Hopkins Medical Institutions, Baltimore, Md.
RELATED ARTICLE
Melanoma: Lessons From Metastases
Jack L. Arbiser
Arch Dermatol. 1998;134(8):1027-1028.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Sentinel Lymph Node Tumor Load: An Independent Predictor of Additional Lymph Node Involvement and Survival in Melanoma
Vuylsteke et al.
Ann. Surg. Oncol. 2005;12:440-448.
ABSTRACT
| FULL TEXT
Cleavage of L1 in Exosomes and Apoptotic Membrane Vesicles Released from Ovarian Carcinoma Cells
Gutwein et al.
Clin. Cancer Res. 2005;11:2492-2501.
ABSTRACT
| FULL TEXT
Quantification of Tumor Vascularity With Contrast-Enhanced Sonography: Correlation With Magnetic Resonance Imaging and Fluorodeoxyglucose Autoradiography in an Implanted Tumor
Fleischer et al.
J Ultrasound Med 2004;23:37-41.
ABSTRACT
| FULL TEXT
Inhibition of Angiogenesis and Promotion of Melanoma Dormancy by Vitamin E Succinate
Malafa et al.
Ann. Surg. Oncol. 2002;9:1023-1032.
ABSTRACT
| FULL TEXT
Mitogen-actived Protein Kinase Activation Is an Early Event in Melanoma Progression
Cohen et al.
Clin. Cancer Res. 2002;8:3728-3733.
ABSTRACT
| FULL TEXT
Persistence of microscopic human cancers in mice: alterations in the angiogenic balance accompanies loss of tumor dormancy
UDAGAWA et al.
FASEB J. 2002;16:1361-1370.
ABSTRACT
| FULL TEXT
Biological Behavior of Human Breast Cancer Micrometastases
Klauber-DeMore et al.
Clin. Cancer Res. 2001;7:2434-2439.
ABSTRACT
| FULL TEXT
Vascular Endothelial Growth Factor as a Target for Antiangiogenic Therapy
Gordon
JCO 2000;18:45s-46.
FULL TEXT
Tumor Biology: Use of Tiled Images in Conjunction with Measurements of Cellular Proliferation and Death in Response to Drug Treatments
Wexler et al.
Clin. Cancer Res. 2000;6:3361-3370.
ABSTRACT
| FULL TEXT
Local Imbalance of Proangiogenic and Antiangiogenic Factors: A Potential Mechanism of Focal Necrosis and Dormancy in Tumors
Ramanujan et al.
Cancer Res. 2000;60:1442-1448.
ABSTRACT
| FULL TEXT
Vasculogenic Mimicry and Tumor Angiogenesis
Folberg et al.
Am. J. Pathol. 2000;156:361-381.
ABSTRACT
| FULL TEXT
Tumor Angiogenesis and Metastasis in Melanoma
Journal Watch Dermatology 1998;1998:1-1.
FULL TEXT
Melanoma: Lessons From Metastases
Arbiser
Arch Dermatol 1998;134:1027-1028.
FULL TEXT
Hypoxia Inhibits G1/S Transition through Regulation of p27 Expression
Gardner et al.
J. Biol. Chem. 2001;276:7919-7926.
ABSTRACT
| FULL TEXT
|
