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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-01-0084.
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Blood, 1 November 2002, Vol. 100, No. 9, pp. 3344-3351
NEOPLASIA
Prognostic value of enhanced bone marrow angiogenesis in
early B-cell chronic lymphocytic leukemia
Stefano Molica,
Angelo Vacca,
Domenico Ribatti,
Antonio Cuneo,
Francesco Cavazzini,
Domenico Levato,
Gaetano Vitelli,
Luigi Tucci,
Aldo M. Roccaro, and
Franco Dammacco
From the Departments of Hematology/Oncology, and
Anatomy and Histopathology, Azienda Ospedaliera
"Pugliese-Ciaccio," Catanzaro, Italy; Department of Biomedical
Sciences and Human Oncology, Section of Internal Medicine and Clinical
Oncology, and Department of Human Anatomy and Histology, University of
Bari Medical School, Bari, Italy; Institute of Hematology, University
of Ferrara, Ferrara, Italy; and Clinical Pathology Service, Institute
"Regina Elena" IRCCS, Rome, Italy.
Because tumor progression is angiogenesis-dependent,
angiogenesis density was investigated by immunohistochemistry and
computed image analysis in bone marrow (BM) biopsies of 45 newly
diagnosed patients with Binet stage A B-cell chronic lymphocytic
leukemia (BCLL) and correlated to upstaging and
progression-free survival during a 40-month follow-up period. Their
microvessel areas and counts were significantly higher than those of
patients with anemia due to iron or vitamin B12
deficiencies. A cutoff value of 0.90 mm2 × 10 2 or greater of the microvessel
area identified patients with earlier upstaging and shorter
progression-free survival. When the cutoff was applied to the Rai
subclassification, both Rai 0 and Rai I-II patients who upstaged and
shortened the progression-free survival were classified correctly.
Information of this type was not given by the microvessel counts. The
cutoff did not correlate with other predictors representative of tumor
mass or disease progression. The microvessel area correlated with the
expression of angiogenic vascular endothelial growth factor (VEGF) by
tumor tissue, and serum levels of VEGF were found to be of prognostic
value. A causal relationship between risk of progression and BM
angiogenesis in BCLL is suggested. A risk stratification inside Rai is
proposed. The prognostic usefulness of BM angiogenesis in patients with BCLL is envisaged.
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