Frequent microsatellite instability in non-Hodgkin lymphomas irresponsive to chemotherapy.
Microsatellite instability (MSI) in haematopoietic malignancies has been controversial. Particularly in non-Hodgkin lymphoma, the data published to date lack unity. Using a unique fluorescent technique, we found MSI in eight (14%) tumours in a panel of 59 carefully selected non-Hodgkin lymphoma patients. Our fluorescent technique also reveals two qualitatively distinct modes of MSI, i.e. Type A and Type B. Based on our previous studies using DNA mismatch repair (MMR) gene-knock out animals, we have concluded that Type A MSI is a direct consequence of defective MMR. MSI observed in non-Hodgkin lymphomas was uniformly Type A, which implies that MMR deficiency occurs in this malignancy. Intriguingly, in non-Hodgkin lymphoma patients treated by CHOP/VEPA-based therapies, response to chemotherapy was significantly worse in those with microsatellite-unstable tumours (p=0.027). As a consequence, the patient outcomes at 1 year after treatment were significantly less favourable in this population (p=0.046), although the survival difference was not statistically confirmed in a longer term. These findings suggest that in some non-Hodgkin lymphomas MMR deficiency may lead to drug resistance in tumour cells and, consequently, to poor patient outcomes. In non-Hodgkin lymphoma, MSI may be a potential biomarker that predicts the tumour response against chemotherapy.
Miyashita
Kaname
K
Institute for Clinical Research, National Kyushu Cancer Center, Fukuoka, Japan.
Fujii
Kei
K
Yamada
Yu
Y
Hattori
Hiroyoshi
H
Taguchi
Kenichi
K
Yamanaka
Takeharu
T
Yoshida
Mitsuaki A
MA
Okamura
Jun
J
Oda
Shinya
S
Muta
Koichiro
K
Nawata
Hajime
H
Takayanagi
Ryoichi
R
Uike
Naokuni
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053843:DNA Mismatch Repair; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005453:Fluorescence; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics
C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein