Background‘Double-hit’ lymphoma (DHL) and ‘double-expression’ lymphoma (DEL) involving gene rearrangement and protein expression of MYC and BCL2/BCL6 have recently become the most commonly used terms to describe the poor prognostic types of diffuse large B-cell lymphoma (DLBCL). However, the clinical and pathological spectra of these rare entities have not been well defined. The aim of this study was to determine the frequency of DHL and DEL in DLBCL and their prognostic impacts in the era of cyclophosphamide, doxorubicin, vincristine and prednisone plus rituximab therapy.MethodsThe data and tissues from 98 patients diagnosed with DLBCL were used in this study. Formalin-fixed and paraffin-embedded tissues were constructed for immunohistochemistry (IHC) and interphase fluorescene in situ hybridisation (FISH) analysis for MYC, BCL6 and BCL2 rearrangements.ResultsThere were 14 cases (14.29%, 14/98) and 34 cases (34.70%, 34/98) of lymphomas with the DHL and DEL of MYC and BCL2/BCL6, respectively. DLBCL patients with MYC/BCL2 rearrangements more frequently had bone marrow involvement (p=0.002), and their tumours were commonly of the germinal centre B cell (GCB) subtype. Patients with MYC+/BCL2 +coexpression were more often assessed using the International Prognostic Index (IPI), (Performance Status) PS score and bone marrow involvement. Patients with MYC+/BCL6 +coexpression were associated with their IPI values, Eastern Cooperative Oncology Group scores and occurrence of B symptoms. Their lymphomas were more often of the non-GCB subtype (p=0.010). Multivariate analysis showed that IPI, bone marrow involvement, rearrangements of BCL2, BCL6 and MYC, expression concurrent with rearrangements and coexpression were all significantly associated with overall survival and progression-free survival, with the exception of MYC+/BCL6 +coexpression.ConclusionsMYC/BCL2 DHL, MYC/BCL6 DHL and MYC/BCL2 DEL are an aggressive B cell lymphoma and patients have a poor prognosis. IPI and bone marrow involvement were independent prognostic factors for DHL and DEL. BCL2, BCL6 and MYC rearrangements translocation, expression concurrent rearrangements and coexpression were were independent prognostic factors for survival.Potential implicationsThe present study analysed the genomic alterations and protein expression levels of MYC, BCL2 and BCL6 using FISH and IHC in Chinese patients with DLBCL.We assessed the frequency, clinicopathological features and the prognostic impacts of DHL and DEL in a cohort of de novo DLBCL patients and evaluated the role of each genetic translocation separately and in combination in order to provide reliable conclusions and practical recommendations for diagnostic workups and prognostic predictions.

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To assess the prevalence and prognostic value of myeloid differentiation factor 88 (MYd88) expression and mutational status in diffuse large B cell lymphoma (dlBcl), a total cohort of 100 patients with dlBcl were studied using immunohistochemistry (iHc) and droplet digital polymerase chain reaction (ddPcr), and the association between MYd88 expression and clinicopathological parameters was analyzed. overall, the positive expression rate of MYd88 protein was 38% and the gene mutation rate was 29%. The positive expression and mutation rates were the highest in the primary central nervous system lymphomas (58.33 and 66.67%, respectively). The coincidence rate of the results of MYd88 expression between iHc and ddPcr results was 73% (73/100). univariate survival analysis showed that age (≥60 years old), high neutrophil/lymphocyte count ratio, low lymphocyte count, c-Myc ≥40%, positive MYd88 protein expression, and gene mutation were associated with poorer prognosis rates. Multivariate survival analysis revealed that MYd88 expression was an independent prognostic factor affecting overall survival. in conclusion, the results of this study demonstrated that MYd88 mutation was a valuable index to evaluate the prognosis of dlBcl. ddPcr can be used as a method for detecting MYd88 mutations, although it was not completely consistent with the results of iHc.

This retrospective study is to explore the clinicopathologic, immunophenotypic, and molecular genetic features of Waldeyer ring B-cell lymphoma (WR-BCL). Tissue arrays from 65 WR-BCL cases were subjected to pathologic and immunophenotypic detections. Expression of Epstein–Barr virus-encoded small RNA (EBER) was detected by in situ hybridization. Interferon regulatory factor 4 (IRF4), BCL-2, BCL-6, and C-myelocytomatosis viral oncogeneav (MYC) gene abnormalities were investigated using interphase fluorescence in situ hybridization. Among the 65 patients, there were 12 nasopharynx cases, 49 tonsil cases, and 4 tongue root cases. Moreover, there were 49 cases of diffuse large BCL (DLBCL) and 16 cases of follicular lymphoma (FL). More than 60% of the patients had Ann Arbor stage III/IV disease, with infiltrated neighboring organs, invaded spleens, and increased lactate dehydrogenase (LDH) levels. Tumor cells were positive for multiple myeloma antigen 1 (MUM1), BCL-2, BCL-6, and C-MYC. EBER expression was detected in lymphoma cells of 2 cases. Alteration frequencies of IRF4, BCL-2, BCL-6, and C-MYC were 24.6%, 32.3%, 27.7%, and 30.7%, respectively. Approximately 67.69% cases had stages 0 to II disease, while 32.31% cases had stage III disease. Five-year overall survival rate was 65.12%. Eastern Cooperative Oncology Group performance status (ECOG) score ≥2 was the only adverse factor for overall survival. IRF4/MUM1, C-MYC, and CD10 expressions were related to poor disease prognosis. WR-BCLs were largely dependent on ECOG, LDH, and bone marrow involvement. WR-DLBCL was associated with poor survival outcomes compared with WR-FL. The WR-DLBCLs have distinct clinicopathologic features, with correlations between the IRF4/MUM1, C-MYC and CD10 expressions, ECOG, LDH, bone marrow involvement, and the disease prognosis.

The KRAS gene mutation is involved in several types of tumors. However, the potential role of the KRAS mutation in human primary and paired metastatic colorectal cancer (CRC) among different nationalities is poorly understood. In the present study, we assessed the relationship between KRAS mutation status and overall survival (OS) and disease-free survival (DFS) in 230 patients with primary and paired metastatic CRC. The KRAS mutation rate in primary CRC tissue was 43.0% (99/230), which was higher than in paired metastatic CRC, which was 31.9% (23/72; P<0.001). Clinicopathologically, the KRAS gene mutation rate was higher in tumors that had infiltrated more deeply (T3, T4) and in lymph node (LN) metastases (N1/N2) (P=0.029 and P=0.010, respectively). The KRAS gene status did not differ between the Han and Uyghur nationalities in both primary and metastatic CRC. In 72 paired cases, the KRAS mutation rate in primary CRC was significantly higher than in metastatic CRC (P<0.001) and in metastatic CRC that had infiltrated more deeply (T3, T4) (P=0.034). In the metastatic cases, the KRAS gene mutation rate was higher in patients aged over 65 years (P=0.035). Specifically, KRAS mutation was correlated with a poorer OS and DFS (P=0.004 and P=0.029, respectively). In our study, 35 patients with wild-type KRAS who received cetuximab targeted therapy had a better DFS than patients with mutant KRAS (P=0.029). The results of the current study demonstrate that the KRAS status is significantly associated with infiltrating LN metastases and the TNM stage in primary CRC. In addition, the results show that the KRAS mutation is significantly more common in primary tumors than in paired metastatic CRC, and the KRAS mutation is correlated with a shorter OS and DFS, as patients with wild-type KRAS who received cetuximab experienced a longer DFS.

Although it has been known that PIK3CA was amplified and PTEN was deficient on protein level in DLBCL, the clinicopathological significance of PIK3CA and PTEN genetic change on DNA level hasn’t been established. Here, in our present study, to understand the clinical significance of genetic status of PIK3CA and PTEN in DLBCL, fluorescent in-situ hybridization (FISH) was employed to evaluate the genetic change of PIK3CA and PTEN in clinical sample tissues consist of 205 cases. Incidentally, to understand the clinicopathological significance of genetic change of PIK3CA and PTEN, Cross-table analysis was used to analyze the association between genetic change of PIK3CA and PTEN versus clinicopathological variables available to us, including age, gender, size, location, international prognosis index, performance state, B-symptom, clinical stage, Extra nodal site, concentration of lactate dehydrogenase, therapeutic effects, treatment and overall prognosis. It was found that PIK3CA was amplified and PTEN was deficient on DNA level, the percentage of amplification and loss was 12.7% (26/205) and 12.2% (25/205), respectively. Additionally, no significant association was observed between genetic change of PIK3CA and PTEN versus clinicopathological variables available. Nor was the significant correlation found between loss of PTEN versus PIK3CA amplification. Our results suggest that PTEN deficiency and amplification of PIK3CA on DNA level was an event in the pathogenesis of DLBCL.

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