WHAT IS BURKITT'S LYMPHOMA?

Burkitt's lymphoma (BL) has been defined on the basis of its characteristic cytomorphology. Although histologically identical, endemic BL and sporadic BL are distinct clinico-anatomical entities. Their morphological identity probably relates to similar chromosomal translocations in both tumours, resulting in c- myc de-regulation and consequent unrestrained proliferation without differentiation. Similar gene rearrangements are found in a proportion of AIDS-related lymphomas that are predominantly extranodal and have the cytomorphology of BL. The term “Burkitt-like lymphoma” (BLL) has been applied to a group of high-grade B-cell lymphomas that appear morphologically intermediate between BL and centroblastic/immunoblastic lymphomas, as detailed in an accompanying paper in this issue. These tumours do not usually show c- myc gene rearrangements. The association of Burkitt's name with such a disparate group of tumours is confusing and new terminology for sporadic BL, AIDS-related BL and BLL is desirable. It is important that clinico-anatomical features, as well as cytomorphology, should be taken into account in the diagnosis of endemic BL. The origin of a case from tropical Africa does not, in itself, imply that it is endemic BL, even more since the AIDS epidemic in that continent. © 1997 John Wiley & Sons, Ltd.     

CHANGES IN Bcl-2 AND p53 EXPRESSION IN RECURRENT B-CELL LYMPHOMAS

The aim of this study was to investigate the changes involved in the evolution of nine cases of recurrent B-cell lymphomas. Using the polymerase chain reaction (PCR) on formalin-fixed, paraffin-embedded tissue from both the primary and the recurrent lymphoma of each case, monoclonality was demonstrated in every tumour. In all nine cases, the recurrent lymphoma was shown to belong to the same clone as the primary lymphoma. Eight of these cases were then investigated by immunohistochemistry for changes in Bcl-2 and p53 expression. Five out of eight of the primary lymphomas showed Bcl-2 overexpression. Two of the three cases initially negative for Bcl-2 expression became positive in the recurrence. One out of eight of the primary lymphomas was positive for p53 expression. Of the seven negative cases, one became positive for p53 expression in the recurrence. Both of the p53-positive cases showed high-grade histology. This study shows that Bcl-2 overexpression is probably an important early event in the development of B-cell lymphomas, although it may occur as a post-neoplastic event. p53 mutation is probably more important as a late event and may be associated with high-grade transformation.     

POSITIVE CORRELATION BETWEEN APOPTOTIC AND PROLIFERATIVE INDICES IN GASTROINTESTINAL LYMPHOMAS OF MUCOSA-ASSOCIATED LYMPHOID TISSUE (MALT)

To understand the role of deregulation of apoptosis in the pathogenesis of gastrointestinal MALT lymphoma, apoptosis has been quantitatively studied in paraffin sections from 40 cases (19 low grade, 21 high grade). The extent of apoptosis was correlated with histological grade, proliferative activity as measured by immunostaining of Ki67 proliferation antigen, and the expression of bcl-2 and p53 oncoproteins, which are known to participate in the regulation of apoptosis. Both apoptotic and proliferative indices were significantly ( P <0·00001) higher in high-grade than in low-grade tumours. Overall, apoptotic indices were negatively correlated with bcl-2 expression, particularly in low-grade tumours in which both strong bcl-2 expression and low levels of apoptosis were observed. Thus, the slow expansion of low-grade MALT lymphoma may partly result from a prolonged life-span of tumour cells, due to bcl-2-mediated blockage of apoptosis. No difference in apoptotic indices was found between p53-positive and p53-negative cases. Furthermore, correlation analysis revealed a significantly positive association between apoptotic and proliferative indices. This supports the current belief that the mechanisms controlling apoptosis and proliferation are both activated during the cell cycle and whether a cell enters the proliferation cycle or the apoptotic process depends on survival factors.     

体细胞超突变与B细胞淋巴瘤

对免疫球蛋白基因超突变的分析让人们对各种B细胞及其肿瘤发生发展有了更深刻的认识。目前公认的是,生发中心前B细胞不含体细胞超突变,而生发中心B细胞和生发中心后B细胞（记忆性B细胞和浆细胞）表现出体细胞超突变。如果肿瘤性B细胞的免疫球蛋白超突变存在于肿瘤的发展中,那么连续获得的突变有可能导致肿瘤细胞行为的改变。一些原癌基因: bcl-6,bcl-2,c-myc也可发生体细胞超突变,与各种恶性淋巴瘤的发生相关联。对上述基因的体细胞超突变机制的共性以及它们相互之间是否有关联尚在深入研究中。     

Apoptosis in colorectal carcinoma occurring in patients aged 45 years and under: relationship to prognosis,mitosis, and immunohistochemical demonstration of p53, c-myc and bcl-2 protein products

The aim of this study was to ascertain whether apoptotic counts have prognostic significance in colorectal cancer and if such counts are related to the expression of proteins implicated in cell cycle regulation. Material from a cohort of patients aged 45 years or less with colorectal carcinoma was re-examined to determine apoptotic and mitotic counts by light microscopy, in addition to assessing p53, c-myc, and bcl-2 protein status by immunohistochemistry. The apoptotic index in the 74 patients who were alive or who had died of colorectal carcinoma ranged from 1·2 per cent to 12·3 per cent and exhibited independent prognostic significance, with high counts predicting better survival (P=0·02). Mitotic counts were not related to survival, despite a close correlation with apoptosis (r=0·85). Tumours regarded as not staining with the CM1 antibody for p53 protein demonstrated higher apoptotic counts, compared with those that stained (medians 5·2 and 4·0 per cent, respectively; P=0·03), but p53 expression was found not to be related to survival. The 68 tumours which stained for c-myc appeared to exhibit higher mitotic counts than those that did not. bcl-2 was detected in only four tumours. The latter two proteins exhibited no apparent relationship to the apoptotic index or survival. Although these results indicate a potential role for apoptotic counting in prognostic prediction in colorectal tumours, this is an uncommon group of patients who exhibited some atypical features. The likelihood of a proportion of cases arising within hereditary non-polyposis colorectal cancer syndrome may limit the application of the findings to a more general population with cancer of the colon and rectum. Further work is required, including critical measurement of reproducibility and assessment of the relative impact of this parameter compared with ‘traditional’ prognostic markers. © 1997 John Wiley & Sons, Ltd.     

腺病毒载体介导bcl-2基因转染在离体和在体状态下对损伤运动神经元的保护作用

本文目的在于观察携带 bcl-2基因的重组腺病毒 (Ad/ s-bcl-2 )在离体和在体条件下对损伤运动神经元的保护作用。采用培养脊髓运动神经元的谷氨酸损伤模型和大鼠坐骨神经切断损伤模型 ,评价重组 bcl-2腺病毒对损伤运动神经元的影响。指标是bcl-2原位杂交和免疫组化反应、台盼蓝拒染法检测培养神经元存活、TU NEL 阳性神经元计数以及脊髓运动神经元 ACh E反应。结果 :(1) Ad/ s-bcl-2可转染离体和在体脊髓运动神经元并使其过表达 bcl-2。 (2 )过表达 bcl-2可延长培养神经元的生存时间。(3 )过表达 bcl-2可显著地减少谷氨酸诱导的原代培养脊髓运动神经元的凋亡以及坐骨神经切断损伤诱导的脊髓运动神经元的凋亡。 (4 )过表达 bcl-2可显著地缓解坐骨神经损伤诱导的神经元内 ACh E的活性降低 ,并加速其恢复。本研究结果提示 :腺病毒载体中介 bcl-2基因转染对离体和在体损伤的运动神经元均具有保护作用     

复方丹参对大鼠脑缺血再灌注后大脑皮层神经细胞凋亡和Bcl-2 mRNA表达的影响

为了探讨中药复方丹参对大鼠局灶性脑缺血再灌注后大脑皮层神经细胞凋亡及Bcl-2mRNA表达的影响和保护作用,本研究采用大脑中动脉内栓线阻断法(MCAO)造成局灶性脑缺血再灌注模型,应用原位末端标记(TUNEL)和原位杂交技术检测大鼠大脑皮层神经细胞凋亡和神经细胞Bcl-2mRNA的表达,并进行图像分析。结果显示:缺血再灌注组凋亡神经细胞主要位于缺血侧大脑皮层缺血边缘区(半暗区);缺血侧大脑皮层缺血边缘区神经细胞Bcl-2mRNA的表达在缺血再灌注2h后升高,随着缺血再灌注时间的延长逐渐增强;复方丹参保护组神经细胞Bcl-2mRNA的表达明显强于缺血再灌组(P<0.01),凋亡神经细胞数明显低于缺血再灌组(P<0.01)。上述结果说明复方丹参可通过上调神经细胞Bcl-2mRNA的表达,抑制神经细胞凋亡,减轻缺血再灌注对大鼠大脑皮层神经细胞的损伤。     

INTERLEUKIN-6 PROMOTER POLYMORPHISM AND LATE-ONSET ALZHEIMER's DISEASE IN THE FINNISH POPULATION

Recently, the involvement of the inflammatory response in Alzheimer's disease (AD) has received considerable attention. The gene encoding for interleukin-6 (IL-6) is interesting since IL-6 has been reported not only to be involved in immune functions but also in AD. We investigated whether the IL-6-174 G/C polymorphism is associated with late onset AD (LOAD) in the Finnish subjects. The G allele was over-represented in ApoE4-LOAD patients but remained unimportant in all and in the ApoE E4 carriers. Interestingly, the G allele frequency was lower in our population in both AD patients and in controls compared to Southern European populations.     

Insight into the role of TSLP in inflammatory bowel diseases

Proinflammatory cytokines are thought to modulate pathogeneses of various inflammatory bowel diseases (IBDs). Thymic stromal lymphopoietin (TSLP), which has been studied in various allergic diseases such as asthma, atopic dermatitis (AD) and eosinophilic esophagitis (EoE), has been less considered to be involved in IBDs. However, mucosal dendritic cells (DCs) induced by various cytokines including TSLP were reported to cause polarization of T cell toward Th2 response, the differentiation of regulatory T-cell (Treg), and secretion of IgA by B cells. In this review, we discuss the concept that decreased TSLP has the potential to accelerate the development of Th1 response dominant diseases such as the Crohn's disease (CD) while increased TSLP has the potential to lead to a development of Th2 cell dominant diseases such the ulcerative colitis (UC). To examine TSLP's role as a potential determining factor for differentiating UC and CD, we analyzed the effects of other genes regulated by TSLP in regards to the UC and CD pathogeneses using data from online open access resources such as NetPath, GeneMania, and the String database. Our findings indicate that TSLP is a key mediator in the pathogenesis of IBDs and that further studies are needed to evaluate its role.     

Recent Advances in Pathology: the 2020 Annual Review Issue of The Journal of Pathology

This year's Annual Review Issue of The Journal of Pathology contains 18 invited reviews on current research areas in pathology. The subject areas reflect the broad range of topics covered by the journal and this year encompass the development and application of software in digital histopathology, implementation of biomarkers in pathology practice; genetics and epigenetics, and stromal influences in disease. The reviews are authored by experts in their field and provide comprehensive updates in the chosen areas, in which there has been considerable recent progress in our understanding of disease. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.