Activation and clinicopathologic significance of AKT/mTOR signaling pathway in diffuse large B-cell lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>(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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>(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).</p><p><b>CONCLUSIONS</b>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.</p>

Microsatellite instability of sporadic colorectal carcinomas and its clinicopathological significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the incidence of microsatellite instability (MSI) in sporadic colorectal carcinoma (CRC) using BAT-25 and BAT-26 loci, and its association with clinicopathological features.</p><p><b>METHODS</b>Microsatellite analysis was performed on tissue samples from 73 primary and 53 metastatic tumors collected at the Department of Pathology, Fudan University Cancer Hospital in 2002. Genomic DNA was extracted from paraffin-embedded tissues. Microsatellite alterations of BAT-25 and BAT-26 were detected using fluorescent PCR followed by fragment analysis on automatic DNA sequencer with GeneScan 3.1 software. A case of hereditary nonpolyposis colorectal cancer syndrome (HNPCC) with known high-frequency MSI (MSI-H) was included as positive control.</p><p><b>RESULTS</b>Eleven out of 73 samples from primary tumors (15.1%) were MSI-positive and significantly associated with patient age, tumor site, differentiation and prognosis (P < 0.05). There was no significant difference between the positive rate of MSI in tissue samples from primary and metastatic sites among the 53 metastatic tumors, being 17.0% and 13.2%, respectively, P > 0.05. Two cases with negative MSI at the primary site but positive at the metastatic sites were observed.</p><p><b>CONCLUSION</b>MSI is a frequent molecular event that may serve as a useful parameter for studying tumor biological behavior. MSI plays a partial role in the metastasis of sporadic CRC, but the role of mismatch repair genes and its exact mechanism remains to be determined. The classification of sporadic CRC according to MSI may be of importance both theoretically and practically.</p>