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Blood, Vol. 95 No. 7 (April 1), 2000:
pp. 2253-2261
Significance of cyclin D1 overexpression for the diagnosis of
mantle cell lymphoma: a clinicopathologic comparison of cyclin
D1-positive MCL and cyclin D1-negative MCL-like B-cell lymphoma
Yasushi Yatabe,
Ritsuro Suzuki,
Kensei Tobinai,
Yoshihiro Matsuno,
Ryo Ichinohasama,
Masataka Okamoto,
Motoko Yamaguchi,
Jun-ichi Tamaru,
Naokuni Uike,
Yuko Hashimoto,
Yasuo Morishima,
Taizan Suchi,
Masao Seto, and
Shigeo Nakamura
From the Department of Pathology and Clinical
Laboratories, Laboratory of Chemotherapy, and
the Department of Hematology and Chemotherapy, Aichi Cancer
Center, Nagoya; the Departments of Medical Oncology
and Pathology, National Cancer Center, Tokyo;
the Department of Pathology, Tohoku University School of Medicine,
Sendai; the Department of Internal Medicine, Fujita Health
University School of Medicine, Nagoya; the Second
Department of Internal Medicine, Mie University School of Medicine,
Tsu; the First Department of Pathology, Chiba University
School of Medicine, Chiba; the Department of
Hematology, National Kyushu Cancer Center, Fukuoka; and the
First Department of Pathology, Fukushima Medical College,
Fukushima, Japan.
Mantle cell lymphoma (MCL) is a distinct clinicopathologic entity of
non-Hodgkin's lymphoma, characterized by a monotonous proliferation of
small to medium-sized lymphocytes with co-expression of CD5 and CD20,
an aggressive and incurable clinical course, and frequent
t(11;14)(q13;q32) translocation. We examined 151 cases of lymphoma with
MCL morphology from a viewpoint of cyclin D1 overexpression, which is
now easily detectable by immunohistochemistry. 128 cases (85%) showed
positive nuclear staining for cyclin D1, while the remaining 23 (15%)
were negative. Except for cyclin D1 immunohistochemistry, current
diagnostic methods, including morphological and phenotypical
examinations, could not make this distinction. Although both the cyclin
D1-positive and -negative groups were characterized by male
predominance, advanced stages of the disease, frequent extranodal
involvement, and low CD23 reactivity, the cyclin D1-positive group
showed a higher age distribution (P = .04), larger cell
size (P = .02), higher mitotic index (P = .01),
more frequent gastrointestinal involvement (P = .05), higher international prognostic index score (P = .05), and
lower p27KIP1 expression (P < .0001). Of
particular interest is that cyclin D1-positive MCL showed significantly
worse survival than cyclin D1-negative lymphoma (5-year survival: 30%
versus 86%, P = .0002), which was confirmed by
multivariate analysis to be independent of other risk factors. These
data suggest that cyclin D1-positive and -negative groups may represent
different entities and that the former closely fits the characteristics
of classical, typical MCL. We therefore propose that cyclin
D1-positivity should be included as one of the standard criteria for
MCL, and that innovative therapies for this incurable disease should be
explored on the basis of the new criteria. (Blood.
2000;95:2253-2261
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