Linkage of expression of chemokine receptors (CXCR3 and CCR4) and cytotoxic molecules in peripheral T cell lymphoma, not otherwise specified and ALK-negative anaplastic large cell lymphoma.
Peripheral T cell lymphoma not otherwise specified (PTCL-N) and ALK-negative anaplastic large cell lymphoma (ALCL) are heterogeneous categories with poor diagnostic reproducibility. To clarify the biologic features of these categories, we investigated the expression of two chemokine receptors, type 1 (Th1/Tc1)-associated CXCR3 and type 2 (Th2/Tc2)-associated CCR4 in 110 PTCL-N and 35 ALK-negative ALCL cases, as well as the expression of cytotoxic molecules (CM). CXCR3 and CCR4 were expressed in 69 (63%) and 37 (34%) of PTCL-N, and in 12 (34%) and 6 (17%) of ALK-negative ALCL, respectively. In PTCL-N, type 1 pattern (CXCR3(+)CCR4(-)) was dominant (52%), whereas in ALK-negative ALCL, 54% were negative for both (P < 0.0001). CM was expressed in 38% of PTCL-N and 51% of ALK-negative ALCL. CM-positive PTCL-N consisted mostly of type 1 disease, which shows type 1 phenotype. In contrast, type 2 pattern (CXCR3(-)CCR4(+)) was recognized in the CM-negative group only. Among type 1 disease, CM-positive cases had a higher female ratio and more aggressive clinical features than CM-negative cases and a poorer prognosis (P = 0.006). Multivariate analysis confirmed that the type 1 phenotype with CM expression was an independent prognostic factor. In both PTCL-N and ALK-negative ALCL, CM-positive type 1 disease had an extremely poor prognosis.
Asano
Naoko
N
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan. naasano@shinshu-u.ac.jp
Suzuki
Ritsuro
R
Ohshima
Koichi
K
Kagami
Yoshitoyo
Y
Ishida
Fumihiro
F
Yoshino
Tadashi
T
Ogawa
Hiroshi
H
Morishima
Yasuo
Y
Nakamura
Shigeo
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D017728:Lymphoma, Large-Cell, Anaplastic / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D054398:Receptors, CCR4 / Q000378:metabolism*; D054367:Receptors, CXCR3 / Q000378:metabolism*; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology; D055815:Young Adult
D014408:Biomarkers, Tumor; C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D054398:Receptors, CCR4; D054367:Receptors, CXCR3