Malignant lymphomas in HIV-seropositive patients. Frequency,features, and prognosis. Report on 31 cases

Summary In a random HIV-seropositive population, malignant lymphomas were diagnosed in 31 patients, of whom 24 (77%) had non-Hodgkin lymphoma (NHL) and 7 (23%) Hodgkin lymphoma (HL). The prevalence of NHL among AIDS patients was 8% (23/279 cases), with a prevalence of 17% among autopsied patients (16/96 cases). No patient with HL had AIDS at the time of diagnosis. In 7 of 23 AIDS patients with NHL (30%) the diagnosis was made only post mortem; among these were all 5 patients with primary CNS NHL. Median survival from the time of diagnosis was 1 month for patients with NHL and 3 months for those with HL. In individual patients, survival for several years may be possible with chemotherapy. Certain patients with NHL appear to benefit from intensive chemotherapy with a combination of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOPB protocol). Appropriate, therapeutic strategies taking into account the patients' individual conditions, including the overall prognosis, urgently requires development. Metastatic CNS involvement, which was the primary cause of death in 5 of 11 patients with NHL (45%) receiving chemotherapy, represents a serious limitation to successful treatment.Abbreviations AIDS acquired immunodeficiency syndrome - CB centroblastic - CDC Centers for Disease Control - CHOP cyclophosphamide, doxorubicin, vincristine, prednisone - CMV cytomegalovirus - CNS central nervous system - COPBLAM cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin, procarbazine - COPP/ABVD cyclophosphamide, vincristine, prednisone, procarbazine/doxorubicin, bleomycin, vinblastine, darcarbazine - CR complete remission - CT computerized tomography - ELISA enzyme-linked immunosorbent assay - HIV human immunodeficiency virus - HL Hodgkin lymphoma - IT intrathecal - IMVP16 ifosfamide, methotrexate, etoposide - KC Kiel classification - MACOP-B methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin - ML malignant lymphoma - NHL non-Hodgkin lymphoma - OI opportunistic infection - PCP Pneumocystis carinii pneumonia - PD progressive disease - PR partial remission - RT radiation therapy - WBC white blood cells - WF Working Formulation     

Different bcl-2 protein expression in high-grade B-cell lymphomas derived from lymph node or mucosa-associated lymphoid tissue.

High-grade B-cell lymphomas, whether originated in a lymph node or in mucosa-associated lymphoid tissue (MALT), show similar morphologic traits, a fact that has fueled a long-running controversy about whether they represent different entities. They differ, however, in that some high-grade MALT lymphomas show less aggressive clinical behavior, a focal low-grade component being identified in some of them. In a search for bcl-2 protein expression, we have found a significant difference between nodal (39/48) and MALT high-grade B-cell lymphoma (1/15) (P less than 0.01). Bcl-2 gene product is an inner mitochondrial membrane protein able to give a survival advantage to B-cell lines by blocking programmed cell death. This protein is usually expressed by memory or resting B cells, most activated B cells being bcl-2 negative, except in lymph-node-originated high-grade B-cell lymphomas, which appear to be mainly bcl-2 positive. Presence of bcl-2 protein in nodal large-cell lymphomas seems to be independent of a t(14;18) translocation, only being found in 19 to 28% of these lymphomas, although it constitutes a definite difference between both tumors, suggesting the existence of different molecular genetic characteristics and pathogenesis, and is possibly related to the more aggressive clinical behavior of nodal high-grade tumors.     

Diffuse aggressive B-cell lymphomas of the gastrointestinal tract. An immunophenotypic and gene rearrangement analysis of 22 cases.

Twenty-two diffuse aggressive B-cell lymphomas of the gastrointestinal tract were studied using light microscopic examination, immunohistochemical methods, and Southern blot analysis. The results suggest that diffuse aggressive B-cell gastrointestinal tract lymphomas may be divided into two groups: large cell lymphomas and small noncleaved cell lymphomas. Large cell lymphomas often involve the stomach; commonly express the lymphocyte adhesion molecules CD44, LFA-1 (CD11a and CD18), and CD54; and may express monotypic cytoplasmic immunoglobulin in approximately one third of cases. Southern blot analysis demonstrates rearrangements of the c-myc gene that do not co-migrate with rearrangements of the immunoglobulin heavy chain gene, as detected with a JH probe in approximately one half of the cases. Small noncleaved cell lymphomas typically involve the ileocecal region. In these lesions, monotypic cytoplasmic immunoglobulin is not detected, and the CD44 and LFA-1 molecules usually are not expressed, particularly in small noncleaved cell lymphomas of the Burkitt type. The CD54 antigen is positive in fewer than one half of cases. Southern blot studies often demonstrate rearrangements of the c-myc gene that co-migrate with immunoglobulin heavy chain gene rearrangements indicative of the t(8;14) chromosomal translocation, with the c-myc region translocated into the immunoglobulin heavy chain gene joining region. Thus, immunohistochemical and genotypic results, in accordance with the site of involvement and histologic findings, suggest a different pathogenesis for large cell lymphomas and small noncleaved cell lymphomas. The findings in large cell immunoblastic lymphomas are more akin to those of the large cell group. In addition, immunophenotypic and molecular data may be helpful in improving histologic classification when the morphologic findings are equivocal.     

The pattern of prion-related protein expression in the gastrointestinal tract

Prion diseases or transmissible spongiform encephalopathies have been shown to be communicated by oral ingestion of the infectious agent. However, the exact route of transmission is still unknown. In order to better understand the pathophysiology of these diseases, it is crucial to identify cell types of peripheral tissues in which the infectious agent may propagate. Since expression of cellular prion protein (PrP^c) is a prerequisite for prion replication, we determined the expression of PrP^c in the mucosa of the gastrointestinal tract using immunohistochemistry. Expression of PrP^c was negative or weak in the neck region of the gastric mucosa and moderate to strong in crypts of both the small and the large bowel. PrP^c was found to be upregulated in the mucosa of patients with Helicobacter pylori gastritis. In contrast, PrP^c staining appeared to be downregulated in patients with inflammatory disorders of the large bowel and it remained moderate to strong in inflammatory disorders of the small bowel. Our results support the notion that epithelial cells of the gastrointestinal tract may represent a possible target for prion entry and replication. Received: 15 September 1999 / Accepted: 23 December 1999     

Primary lymphomas of the gastrointestinal tract I. Plasma cell tumours

The histology of 125 cases of primary gastrointestinal lymphomas arising in the stomach and small and large intestine has been reviewed. The material was gathered from the Bland-Sutton Institute of Pathology at the Middlesex Hospital and from the Westminster Hospital. Of the initial total of 143 cases diagnosed, 18 were rejected. Of the acceptable 125 cases, 51 lymphomas were arising in stomach, 53 in the small intestine and 21 in the large intestine including rectum. Excluding the four children in the series, ages ranged from 18 to 82 and were fairly evenly distributed across the decades. There was no significant sex difference in the Middlesex Hospital cases but in the Westminster Hospital series the male to female ratio was approximately 2.6 to 1. One significant finding to emerge from this histological survey, and which forms the basis of this communication, is the proportion of lymphomas considered to be predominantly of plasma cell type. These plasma cell tumours, or extramedullary plasmacytomas, accounted for 49 out of the 125 cases (39%) of gastrointestinal lymphomas. They were less common in stomach and most common in the intestine, the majority occurring in the ileocaecal region. Conversely, Hodgkin's disease, in contrast to some series, was not encountered. Of the non-Hodgkin's lymphomas, grade I tumours were uncommon and true histiocytic lymphomas were distinctly rare. The high incidence of plasma cell tumours were uncommon and true histiocytic lymphomas were distinctly rare. The high incidence of plasma cell tumours in our series is in keeping with the morphological findings of a previous study carried out in patients with alpha-chain disease and in a small series of primary gastrointestinal lymphomas.     

Expression of the bcl-2 protein in B cell lymphomas arising from mucosa associated lymphoid tissue.

AIM--To determine whether lymphomas arising from mucosa associated lymphoid tissue (MALT) express the bcl-2 protein. METHODS--Forty two cases of MALT B cell lymphomas, 20 low grade neoplasms and 22 high grade tumours, were studied. Immunohistological staining was performed on paraffin wax embedded tissue using a monoclonal antibody specific for the bcl-2 protein. RESULTS--All of the low grade lymphomas gave positive results on staining, with clear cytoplasmic labelling for bcl-2 protein in the small neoplastic cells, some of which formed characteristic lympho-epithelial lesions. A striking feature was that larger bcl-2 negative cells were observed in nine of these tumours. They were either scattered singly among the small neoplastic cells or formed small clusters, suggesting that they could represent early areas of transformation to high grade neoplasia. Germinal centres in the vicinity of the tumours lacked bcl-2 protein and hence contrasted clearly with the neoplastic cells. In some cases this permitted germinal centres, which were not obvious on conventional histological staining, to be recognised. In 20 of the 22 cases of high grade B cell lymphoma the large neoplastic cells were bcl-2 negative; the remaining two cases, however, contained a proportion of large neoplastic bcl-2 positive cells. In four of the 22 cases of high grade tumours a low grade component was found which expressed bcl-2 in all cases. CONCLUSION--Bcl-2 protein is expressed in low grade, but not in most high grade, MALT lymphomas. In view of recent data indicating that most high grade nodal lymphomas express bcl-2, these findings suggest that MALT lymphomas may regulate bcl-2 gene expression differently to nodal lymphomas.     

Cyclooxygenase-2 expression in stromal tumors of the gastrointestinal tract

Cyclooxygenase (COX) is a key enzyme in the conversion of arachidonic acid to prostaglandins, prostacyclin, and thromboxane. COX-2 is expressed in many epithelial malignancies, particularly those of the gastrointestinal (GI) tract. COX-2 has been implicated in the pathogenesis of cancers and has a significant negative effect on survival. To date, little is known about the expression of COX-2 in nonepithelial tumors. The objective of this study was to evaluate the expression of COX-2 in GI stromal tumors (GISTs). We evaluated 15 GISTs using tissue microarray. Tissue blocks were retrieved and stained with hematoxylin and eosin to evaluate the histological tumor type. In addition, immunohistochemistry was performed for COX-2, the macrophage marker, CD68 (KP-1), and KIT (CD117). Two pathologists then evaluated the tissues to determine the extent and intensity of COX-2 expression. The location of CD68-positive cells, and whether these cells were COX-2 positive, was also evaluated. The results showed that 80% (12 of 15) of the tumors expressed COX-2. Expression was noted in the cytoplasm of the tumor cells, with variable intensity of staining among the tumors. COX-2 was expressed in both epithelial cell and spindle cell tumors, but appeared stronger in epithelial lesions. In mixed lesions, COX-2 was expressed to a greater extent in epithelial areas. There was a greater extent of COX-2 expression in malignant tumors and tumors located within the stomach. Tumor-infiltrating macrophages (CD68-positive cells) were identified in all of the lesions; in 80% of cases, those macrophages also expressed COX-2. This study is the first to demonstrate COX-2 expression in stromal lesions of the GI tract. The enzyme may play a role in the proliferation of these lesions, suggesting the potential use of nonsteroidal anti-inflammatory drugs in treatment.     

Non-Hodgkin's lymphomas of the gastrointestinal tract. An evaluation of paraffin section immunostaining.

Although the gastrointestinal (GI) tract is the most common site of primary extranodal lymphomas, the lineage of these tumors has been controversial. The authors used paraffin-reactive antibodies detecting markers of B-, T-, histiocytic, and epithelial cells to study 34 non-Hodgkin's lymphomas of the GI tract for which unequivocal frozen-section immunophenotypine was available as a control to determine whether these antibodies are reliable in the study of these tumors. Frozen-section studies revealed 31 tumors of B-cell origin and three T-cell tumors. Paraffin-reactive antibodies confirmed B-cell lineage in 28 of the 31 cases, with equivocal results in the remaining three. Only one of the T-cell lymphomas was identified in paraffin studies. Our results indicate that paraffin-reactive antibodies can reliably identify most B-cell lymphomas in the GI tract but may be unreliable in the detection of lymphomas of T-cell origin.     

Angiodysplasia of the gastrointestinal tract: description of 2 cases

Gastrointestinal angiodysplasia is an acquired and degenerative lesion characterized by proliferation and ectasias of the vessels of the mucosa and submucosa. It's thought to be one of the most common causes of lower gastrointestinal bleeding in the elderly. We describe two cases of angiodysplasia and review the related literature.     

bcl-2 and p53 protein expression in follicular lymphoma

Recent studies have shown bcl-2 to be regulated by p53. Other studies have suggested an inverse relationship between p53 and bcl-2 protein expression in breast and colonic cancers and in a variety of subtypes of non-Hodgkin's lymphoma. This study investigates the relationship between bcl-2 and p53 protein expression and the correlation between these findings and the grade and cell type of follicular lymphomas according to the REAL classification. Paraffin-embedded nodal follicular lymphomas (n=37) were subjected to bcl-2 and p53 immunohistochemistry on tissue sections using a three-step ABC system. Positive immunostaining for both oncoproteins was scored using a three-tiered scale: +, <10 per cent cells; ++, 10–50 per cent cells; and +++, >50 per cent cells (<10 per cent was used as a cut-off to define negative tumours). Ninety-seven per cent (36/37) of follicular lymphomas expressed bcl-2 protein in all three grades, manifesting in the small cell (grade 1) through to the large cell (grade 3). p53 protein expression showed a pattern of increasing immunostaining with progression towards the high-grade follicular lymphoma: grade 1=6 per cent (1/16); grade 2=48 per cent (10/21); grade 3=100 per cent (6/6). Five cases comprised varying combinations of grades. This latter finding suggests a role for p53 mutation in the progression/transformation of follicular lymphoma. The mechanism, however, differs from that suggested in breast and colonic cancers, since an inverse relationship between bcl-2 and p53 was not demonstrated in the present study. © 1997 John Wiley & Sons, Ltd.     

Pathologic features and expression of insulin-like growth factor-2 in adrenocortical neoplasms

We analyzed a series of adrenocortical neoplasms to compare the clinicopathologic features and the expression of insulin-like growth factor-2 (IGF-2) in adrenocortical adenomas and carcinomas. IGF-2 is a growth factor commonly expressed in many tumors including adrenal cortical and medullary neoplasms. Formalin-fixed paraffin-embedded tissues from 64 adrenocortical adenomas and 67 adrenocortical carcinomas were analyzed. The carcinomas were histologically graded from 1 to 4 based on mitotic activity and necrosis. Tumor weight, size, and follow-up information were obtained by chart review. Expression of IGF-2 was detected by immunohistochemistry with the avidin-biotin-peroxidase complex method and a monoclonal antibody against IGF-2. Adrenocortical carcinomas were larger (mean: 13.1 cm, 787 g) than adenomas (mean: 4.2 cm, 52 g) (p<0.001). In patients with adrenocortical carcinomas, high tumor grade (3 or 4) (p=0.01) was associated with decreased survival. Expression of IGF-2 was higher in adrenocortical carcinomas than in adenomas (p<0.001). These results show that tumor size and weight along with expression of IGF-2 protein are useful features to assist in distinguishing between adrenocortical adenomas and carcinomas, and that high tumor grade is a predictor of survival in adrenocortical carcinomas. However, single immunohistochemical markers such as IGF-2 or single histopathologic features cannot by themselves separate adrenocortical adenomas from carcinomas, and a combination of clinical, gross, and microscopic features are needed to establish the diagnosis in difficult cases.     

不同类型淋巴瘤中survivin和bcl-2的表达及意义

目的　探讨检测抗凋亡基因survivin和bcl- 2在不同类型淋巴瘤的表达及对淋巴瘤诊断和分型的意义。方法　石蜡标本制作组织芯片,应用免疫组化S P法检测219例淋巴瘤及13例反应性增生淋巴结石蜡标本中survivin和bcl 2表达;同时应用RT PCR技术检测18例淋巴瘤、2例淋巴结反应性增生survivin和bcl- 2mRNA表达,并进行半定量分析。结果　survivin在弥漫性大B细胞淋巴瘤(diffuselargeBcelllymphoma,DLBL) (88. 6%, 70 /79)、淋巴母细胞淋巴瘤(lymphoblasticlymphoma,LBL) (92 3%, 12 /13)、伯基特淋巴瘤(Burkitt slymphoma,BL) (2 /2)有较高的表达;而在滤泡性淋巴瘤(follicularlymphoma,FL)、黏膜相关淋巴组织边缘区B细胞淋巴瘤(extranodalmarginalzoneB celllymphomaofmucosa associatedlymphoidtissuelymphoma,MALTL)和淋巴结边缘区B细胞淋巴瘤(marginalzonelymphoma,MZL)中表达较低,且多为弱阳性。高表达组与低表达组之间差异有统计学意义(P<0. 01 )。bcl- 2在小淋巴细胞淋巴瘤(smalllymphocyticlymphoma,SLL)、套细胞淋巴瘤(mantlecelllymphoma,MCL)、外周T细胞淋巴瘤(peripheralTcelllymphoma,PTL)、间变性淋巴瘤(anaplasticlargecelllympho ma,ALCL)、DLBL和FL有较高的表达,但各组间差异无统计学意义(P     

Significantly different bcl-2 expression profiles in gastric and non-gastric primary extranodal high-grade B-cell lymphomas

Fifty-five cases of primary extranodal high-grade B-cell non-Hodgkin's lymphoma were investigated for bcl-2 and p53 protein expression as well as for t(14;18) translocations and p53 mutations. Phenotypic and genotypic profiles were compared between tumours of gastric (27 cases) and non-gastric (28 cases) origin. bcl-2 protein expression was significantly lower in gastric (11/27) than in non-gastric (28/28) lymphomas (p<0.0001), while nuclear p53 protein expression did not differ significantly between these two groups. In the stomach, there were no significant differences in either bcl-2 or p53 expression profiles between high-grade lymphomas with (n=14) and without (n=13) evidence of a low-grade component of MALT type. However, secondary high-grade lymphomas showed a significant down-regulation of bcl-2 protein (p<0.0001) and, conversely, an up-regulation of p53 protein (p<0.0001) as compared with their low-grade tumour components. In extranodal high-grade B-cell lymphomas, bcl-2 protein expression was not associated with t(14;18) translocation. Only one gastric lymphoma had a p53 point mutation with potential alteration of the amino acid sequence. These findings indicate that primary gastric high-grade B-cell lymphomas are immunohistologically distinct from primary extranodal high-grade B-cell lymphomas of an origin other than in the stomach.     

p53 and bcl-2 protein expression in non-small-cell lung carcinoma

The diagnostic significance of p53 and bcl-2 proteins in epithelial non–small-cell lung cancers was examined, and the relationship between these proteins expression and other disease parameters, including stage of the disease and tumor differentiation, were studied. We analyzed p53 and bcl-2 proteins expression in 60 imprint smears of freshly resected lung tumors (37 squamous and 23 adenocarcinomas) using the immunocytochemical technique. There were seven patients with stage I disease, 24 with stage II, 23 with stage IIIa, and six with stage IIIb disease, according to the International Staging System classification. Sixteen of the tumors were bcl-2 positive and 25 were p53 positive. Twenty tumors were negative for both bcl-2 and p53 (33.3%). Statistical analysis showed no association between the incidence of p53 or bcl-2 positivity. Adenocarcinoma or squamous carcinoma analysis showed significant associations between p53 positivity and poor differentiation and advanced disease stage as well as bcl-2 and early disease stage and well-differentiated tumors. There was also an association between the stage of the disease and the degree of differentiation of the tumors. In conclusion, bcl-2 positivity must be considered a good prognostic sign. On the other hand, p53 positivity seems to indicate, even in tumors at a relatively early stage, that a serious aggressive tumor which will not be easily eradicated is present. Diagn. Cytopathol. 1998;19:255–259. © 1998 Wiley-Liss, Inc.     

The bcl-2 proto-oncogene and the gastrointestinal epithelial tumor progression model.

We report overexpression of the proto-oncogene bcl-2 in gastrointestinal adenocarcinoma and its precursor lesions. The bcl-2 proto-oncogene is centrally involved in the oncogenesis of human follicular lymphoma via a chromosomal translocation t(14;18)(q32;q21) and is also expressed in the epithelial regenerative compartment or the basal crypts of the normal colon and small intestine. We describe an immunohistochemical analysis of fixed, paraffin-embedded tissue using both a polyclonal rabbit and a monoclonal mouse antibody to the Bcl-2 protein. In addition to confirming bcl-2 expression in normal colonic and small intestinal crypts, we also observed expression in the gastric epithelial regenerative compartment, the mucous neck region. No increased expression was found in nonneoplastic or inflammatory gastrointestinal conditions, including ulcerative colitis, Crohn's disease, or inflammatory or hamartomatous polyps. Increased bcl-2 expression, however, was present in hyperplastic colonic polyps and in the majority of dysplastic lesions, from the earliest precursors through large adenomas, high grade flat dysplasia, and adenocarcinoma, all in comparison with adjacent internal control normal epithelium. Increased expression was present in dysplastic glandular lesions from all gastrointestinal sites, including colon, small bowel, and stomach. Furthermore, bcl-2 expression was frequently abnormal in nondysplastic epithelium surrounding dysplastic lesions, suggesting that altered expression occurred before the development of morphological dysplasia. Specifically, directly contiguous morphologically nondysplastic epithelium often showed abnormal bcl-2 expression throughout the full length of the crypt-villus axis. This expression pattern gradually diminished to involve only the crypt base (the normal pattern of expression), proceeding away from malignant or dysplastic lesions. Abnormal bcl-2 immunoreactivity in 1), the earliest precursor dysplastic lesions and its persistence throughout neoplastic progression and 2), contiguous morphologically unaltered nondysplastic epithelium suggests that bcl-2 alterations occur early during the morphological and molecular sequence of events leading to gastrointestinal epithelial neoplasia.     

Schwannomas of the gastrointestinal tract: clinicopathological features of 12 cases including a case of esophageal tumor compared with those of gastrointestinal stromal tumors and leiomyomas of the gastrointestinal tract

We analyzed the clinicopathological features of 12 gastrointestinal (GI) schwannomas and compared them with those of 37 GI stromal tumors (GISTs) and 15 leiomyomas. Grossly, the schwannomas showed rubbery to firm, yellow-white to tan, glistening, and often trabeculated cut surfaces, resembling soft tissue schwannomas. The GISTs were firm to soft or fish-flesh tan, gray-pink, or variegated tumors with a degenerative change, and the leimyomas resembled typical uterine leiomyomas. Histologically, GI schwannomas were moderately cellular tumors with focal significant nuclear pleomorphism and rare mitotic figures. A characteristic peripheral lymphoid cuff was observed in all cases, but was indistinct in two cases. The GISTs were highly cellular spindle cell, epithelioid or, occasionally, pleomorphic tumors with basophilic appearance. Leiomyomas were paucicellular tumors with eosinophilic appearance. Immunohistochemically, schwannomas were S-100 protein- and glial fibrillary acidic protein (GFAP)-positive, but were negative for c-kit, CD34, and smooth muscle actin (SMA). GISTs were all c-kit- and/or CD34-positive, but GFAP-negative. Leiomyomas were SMA-positive and were negative for c-kit, CD34, S-100 protein, and GFAP. The mean Ki-67 index of schwannoma was 0.7, and those of GIST and leiomyoma were 5.9 and 0.3, respectively. The patients with schwannomas and leiomyomas had a favorable outcome, whereas 12 patients with GISTs showed progression and died of disease. The separation of GISTs from schwannomas is clinically important because the former group has a high risk of malignant behavior. GI schwannomas differed from the conventional soft tissue schwannomas in that they had peripheral lymphoid cuffs, lacked fibrous capsule and vascular hyalinization, and rarely showed degenerative changes. GI schwannomas, however, resembled soft tissue schwannomas in many aspects, and the clinical, gross, histological, and immunohistochemical features were different from those of GISTs and leiomyomas.     

Frequency and clinicopathological features of fibroelastotic changes in the gastrointestinal tract

Fibroelastotic changes (FEC) and especially elastotic polyps of the gastrointestinal (GI) tract are considered rare benign lesions. They consist of accumulations of elastic fibers within the mucosal, submucosal, or muscular layer, occurring in all parts of the GI tract and often appearing as polyps, but also as diffuse non-polyp-forming deposits. They have been the subject of only a few studies. To explore the clinical and histopathological features of FEC in the GI tract, a series of 162 elastotic lesions was collected within a 2-year period. The clinical data and endoscopic findings were correlated. FEC appeared as polyp-forming lesions of the large intestine in 23 samples (14 %), all other samples concerning histological findings without an identifiable gross mass. Frequently related findings were postinterventional status (9 %), previous irradiation (7 %), and history of GI lymphoma (4 %). Eight samples (5 %) presented endoscopically with lesions justifying surgical intervention. We identified three different histological patterns of FEC, which we have called fibroelastosis, angioelastosis, and elastofibroma. Consistent with previous studies, CD34 immunohistochemical staining (performed on 38 polypoid FEC specimens) showed an increase of CD34-positive mesenchymal cells in 95 % of immunostained samples, suggesting a potential role for CD34-positive mesenchymal cells in the accumulation of elastic fibers. In conclusion, FEC are more common in the GI tract than previously recognized. They often present as a benign polyp. Many accompany other diseases like ulcers and atrophic gastritis or represent a residual finding after an intervention.     

Developmental regulation of bcl-2 expression in the thymus.

An important factor in shaping the T-cell receptor (TcR) repertoire during thymocyte development is the susceptibility of double-positive (CD4+ CD8+) thymocytes to induction of apoptosis (negative selection) when the TcR is engaged by 'self'-antigens. Recent evidence has suggested that this susceptibility to apoptosis may be influenced by the expression of bcl-2, a proto-oncogene known to increase the resistance to apoptosis in various cell systems. Using a semi-quantitative polymerase chain reaction (PCR) technique in conjunction with staged embryonic material and purified thymocyte subpopulations we have investigated patterns of bcl-2 expression during normal T-cell development. Our results show that while bcl-2 alpha gene expression is readily detectable in immature CD3-CD4-CD8- thymocytes and in mature single-positive TcRhi cells, it is drastically reduced in TcR negative double-positive (CD3- CD4+ CD8+) cortical thymocytes of intermediate maturity. Careful mapping of bcl-2 alpha re-expression in relation to the onset of TcR expression within the population of embryonic thymocytes indicates that bcl-2 alpha is up-regulated as soon as TcR molecules are expressed on the surface of CD4+ CD8+ thymocytes. Therefore, thymocytes susceptible to apoptosis on TcR ligation express bcl-2 alpha mRNA suggesting that changing levels of bcl-2 expression are unlikely to be the only determinant regulating susceptibility to apoptosis in the thymus. The possible implications of these changes in bcl-2 expression regarding other facets of thymocyte development will be discussed.     

Apoptosis and expression of bcl-2 protein in invasive ductal adenocarcinoma of the pancreas

Apoptosis plays a central role in the development and/or progression of cancer. There are several methods for detection of apoptotic cells in tissue sections including light and electron microscopy, in situ nick end-labeling (ISEL), TdT-mediated dUTP nick-end labeling (TUNEL) and immunohistochemical detection of proteins associated with apoptosis. Apoptosis was assessed by the monoclonal antibody M30 CytoDEATH (M30), which is specific for neo-epitope in cytokeratin 18 that becomes available at an early caspase cleavage during apoptosis. Expression of bcl-2 protein was evaluated, because bcl-2 protein plays an important role in the regulation of apoptosis. Twenty-six invasive ductal adenocarcinomas of the pancreas were studied immunohistochemically with antibodies M30 and bcl-2. The mean apoptotic index (AI, the percentage of apoptotic cells of the total tumor cells number) was 2.75%. High AI (> 10%) was observed in 4 cases of the 26 pancreatic carcinomas (15%). Protein bcl-2 was expressed in 3 cases (11.5%). The AI did not correlate with the expression of protein bcl-2. In conclusion, the detection of neo-epitope in cytokeratin 18 by monoclonal antibody M30 can be used for quantification of apoptotic cells with immunohistochemical techniques in tissue sections. It is a new approach to evaluate apoptosis in pancreatic carcinomas. The low positivity of bcl-2 expression in pancreatic adenocarcinomas suggests that bcl-2 protein does not play a central role in pancreatic tumorigenesis and cancer progression.     

胃肠MALT淋巴瘤中bcl-10 mRNA和蛋白的表达

目的　探讨bcl- 10基因在胃肠黏膜相关淋巴组织(MALT)淋巴瘤中的表达情况及意义。方法　采用免疫组化S P 法及原位杂交技术检测40例胃肠MALT淋巴瘤和14例正常淋巴结中bcl- 10基因的表达。结果　40例MALT淋巴瘤中有36 例(90.0%)表达bcl- 10蛋白,其中21例仅在胞质表达,15例在胞质胞核同时表达;39例(97.5%)表达bcl 10mRNA。bcl -10 蛋白与mRNA表达之间差异无统计学意义(P>0.05)。MALT淋巴瘤临床分期与bcl- 10蛋白核表达明显相关(P<0.01)。14 例淋巴结中,8例(57.1%)表达bcl -10蛋白。淋巴滤泡内生发中心B细胞呈高度表达,边缘区B细胞中等强度表达,套区细胞 微弱表达。结论　bcl -10的高度表达在MALT淋巴瘤发生发展可能起着重要作用。bcl -10蛋白核表达与进展期MALT淋巴瘤 相关。bcl -10蛋白在淋巴滤泡各区域的表达差异提示它对B细胞分化成熟有着重要意义。