[Activation and clinicopathologic significance of AKT/mTOR signaling pathway in diffuse large B-cell lymphoma].
OBJECTIVE
(1) To investigate the activation of AKT/mTOR signaling transduction pathway in DLBCL and its association with the expression of bcl-6 and some other clinical pathologic factors. (2) To estimation of the signaling pathway function in diverse subtypes of DLBCL and its potential value in the targeted treatment of DLBCL.


METHODS
Immunohistochemical (IHC) EnVision staining was used to detect the expressions of pAKT and pmTOR in 100 DLBCL and 10 reactive hyperplasia fresh lymph node samples; TaqMan real-time reverse transcription polymerase chain reaction (real-time RT-PCR) technique was used to explore the expression of bcl-6 mRNA in the DLBCL samples. IHC staining was used to detect the expressions of bcl-6, CD10 and MUM1 in 75 of the 100 corresponding paraffin-embedded samples and these 75 DLBCL samples were subdivided into GCB and non-GCB subgroups.


RESULTS
(1) The expression of pAKT and pmTOR was 76% (76/100) and 75% (75/100), respectively, and the expression of the two proteins correlated with each other. (2) The expression of bcl-6 protein and mRNA significantly correlated with each other. The expression of bcl-6 protein and mRNA in pAKT and pmTOR high-expression group was significantly lower than that in low-expression group (both P < 0.01). (3) The expression of pAKT and pmTOR in non-GCB group was 82.5% (47/57) and 84.2% (48/57), respectively, which were significantly higher than that in GCB group, which showed an expression rate of 44.4% (8/18) and 44.4% (8/18), respectively (both P < 0.01). (4) The expression of pAKT and pmTOR in male was higher than that in female, and the percentage of patients with abnormal LDH in pAKT and pmTOR positive groups was higher than that in negative groups, although there were no statistical significance (both P > 0.05). There was no relationship between the expression of pAKT and pmTOR and age, sex, stage, KPS and B symptoms (P > 0.05).


CONCLUSIONS
Activation of AKT/mTOR signaling pathway plays an important role in the development of DLBCL, and it is closely related to the low or non-expression of bcl-6 and non-GCB subgroup. Molecules in this pathway might serve as the new targets in the treatment of certain group of DLBCL.
Yu
Bao-hua
BH
Department of Pathology, Cancer Hospital, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Zhou
Xiao-yan
XY
Xiao
Xiu-ying
XY
Yan
Shi-yan
SY
Qin
Tao
T
Shi
Da-ren
DR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012737:Sex Factors; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D055815:Young Adult; D000099218:Interferon Regulatory Factor-4
D050835:Interferon Regulatory Factors; D015260:Neprilysin; D051057:Proto-Oncogene Proteins c-akt; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D058570:TOR Serine-Threonine Kinases; D000099218:Interferon Regulatory Factor-4; C546842:MTOR protein, human