PubMed Health⌕ Search

Biomedical subjects

Jerzy Stachura

Publications and source records attributed to Jerzy Stachura.

At least 19 recordsLinked to original sources
PubMed2006

Loss of Ku70/Ku80 expression occurs more frequently in hereditary than in sporadic colorectal tumors. Tissue microarray study.

Ku70 and Ku80 proteins take part in the repairing of DNA double-strand breaks by their function as a regulatory subunit of the DNA-dependent protein kinase. In this study, expression of both genes was analyzed in colorectal carcinoma tissue arrays applying immunohistochemistry. Expression of both genes decreased along with pT stage. Significant differences in Ku70 and Ku80 expression were found between pT3 and pT4 as well as between pT2 and pT3 tumors, respectively. Loss of Ku70/Ku80 expression was more frequently observed in hereditary than in sporadic tumors. We conclude that expression of Ku70/Ku80 genes is down-regulated in colorectal carcinoma and that defects of these genes are more frequently observed in hereditary than in sporadic tumors.

Adult↗
PubMed2006

GISTs with PDGFRA exon 14 mutations represent subset of clinically favorable gastric tumors with epithelioid morphology.

Gastrointestinal stromal tumors (GISTs) are common mesenchymal tumors of the gastrointestinal tract. Activating KIT or PDGFRA (platelet-derived growth factor receptor alpha) mutations have been shown to be a major force in GIST pathogenesis. Recently, a previously undescribed N659K PDGFRA exon 14 mutation has been reported in GISTs. The purpose of this study was to evaluate the frequency of GISTs with PDGFRA exon 14 mutations and define the clinicopathologic profile of such tumors. In all, 200 GISTs negative for mutations in KIT exons 9, 11, 13 and 17 and PDGFRA exons 12 and 18 were evaluated for PDGFRA exon 14 mutations by PCR amplification and direct sequencing. Mutations were found in 11 of 119 (9%) gastric GISTs. None of the 81 GISTs from other than gastric location had such a PDGFRA mutation. A majority of these mutations (eight cases) represented simple 2125C>A or C>G missense mutations, leading to substitution of the lysine for asparagine (N659K). However, in two cases, 2123A>T missense mutations leading to substitution of the tyrosine for asparagine (N659Y) was found instead. Of 11 PDGFRA N659-mutant GISTs, 10 had pure epithelioid morphology. One tumor had mixed, predominantly spindle and focally epithelioid cell morphology. Frequency of PDGFRA N659-mutant GISTs among pure epithelioid GISTs was almost 19%. Immunohistochemically, the majority (64%) of these tumors lacked KIT expression or showed only focal scattered KIT positivity. Tumor size ranged from 2.5 to 16 cm (average 7.1 cm). Low mitotic activity, 5 cm tumors. Based on mitotic activity and tumor size, six tumors were classified as probably benign with very low malignant potential. Low to moderate malignant potential and high malignant potential was suggested in three and two tumors, respectively. In four cases with moderate or high malignant potential GISTs, a long-term follow-up (average 235.5 months) showed favorable course of disease.

Base Sequence↗
PubMed2006

Clonal lymphocytic populations in Philadelphia-negative chronic myeloproliferative disorders: is the T-cell clonality of 'undetermined' significance (TCUS) linked to a worse clinical outcome?

This study examined the clonality of B- and T-cells by PCR in 83 patients with Philadelphia-negative myeloproliferative disorders (Ph-MPD), to investigate its clinical and morphological correlates. Clonal lymphocytic populations were found in 23% of patients (T: n = 20, B: n = 3), with no frequency differences between ET, CIMF and PV. At the presentation, patients with clonal bands were older (58.1+/-13.8 vs 47.5+/-14.6, p = 0.0039), but did not differ in other clinical parameters. After the median follow-up of 21 months they were less likely to be asymptomatic (11.8% vs 41.1%, p = 0.029). The T-cell clonality was the strongest predictor of the symptomatic last follow-up by discriminant function analysis, surpassing the patient's age. This surprising negative prognostic impact of lymphocyte clonality in Ph-MPD may result from this phenomenon to be a better measure of the 'hematopoietic biologic age' than the metrical age itself.

Biopsy↗
PubMed2006

CDH1 gene promoter hypermethylation in gastric cancer: relationship to Goseki grading, microsatellite instability status, and EBV invasion.

Hypermethylation of the CDH1 promoter region seems to be the most common epigenetic mechanism in this gene silencing in gastric cancer. In this study, CDH1 promoter hypermethylation was observed in 54.8% (46/84) of the analyzed sporadic gastric carcinomas. We introduce a new relation: clustering of Goseki grading into 3 grade was determined by CDH1 promoter hypermethylation. The percentage of methylation in Goseki III cancers was significantly higher (83%) when compared with other grades; the lowest proportion was detected in IV (36%) and II (38%) groups, whereas grade I demonstrated typical percentage of promoter hypermethylation. A novel polymorphism R732R in exon 14 of the CDH1 gene was detected by mutational analysis. Additionally, all cases with the MSI-high phenotype revealed CDH1 promoter hypermethylation. In MSI-low and MSS gastric cancers, this percentage was lower, reaching 71% and 41%, respectively. Moreover, the methylation status was correlated with the LOH phenotype. We detected CDH1 promoter hypermethylation in all EBV-positive gastric cancers (5/5), whereas methylation in the EBV-negative group occurred in 58% of cases. We also report that "methylated" tumors were slightly larger than "nonmethylated," whereas the second group revealed a higher probability of longer patient survival, though these relationships were not statistically significant. These results suggest that downregulation of E-cadherin, caused by promoter hypermethylation, in sporadic gastric carcinomas may be associated with a worse prognosis and specific tumor phenotype.

Adult↗
PubMed2006

Effect of probiotics and triple eradication therapy on the cyclooxygenase (COX)-2 expression, apoptosis, and functional gastric mucosal impairment in Helicobacter pylori-infected Mongolian gerbils.

BACKGROUND: Helicobacter pylori infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis that mimics H. pylori-positive patients developing gastric ulcer and gastric cancer, but the effect of probiotic therapy on functional aspects of this infection remains unknown. METHODS: We compared the effects of intragastric inoculation of gerbils with H. pylori strain (cagA+ vacA+, 5 x 10(6) colony forming units/ml) with or without triple therapy including omeprazole, amoxicillin, and tinidazol or probiotic bacteria Lacidofil. Histology of glandular mucosa, the viable H. pylori, and density of H. pylori colonization were evaluated. The gastric blood flow was measured by H2-gas clearance method; the plasma gastrin and gastric luminal somatostatin were determined by RIA and expression of cyclooxygenase (COX)-2 and apoptotic Bax and Bcl-2 proteins were evaluated by Western blot. RESULTS: The gastric H. pylori infection was detected in all animals by histology and H. pylori culture. Basal gastric acid was significantly reduced in H. pylori-infected animals but not in those with triple therapy or Lacidofil. Early lesions were seen already 4 weeks upon H. pylori inoculation and consisted of chronic gastritis and glandular atypia associated with typical regenerative hyperplasia and increased mitotic activity and formation of apoptotic bodies. The H. pylori infection was accompanied by the fall in gastric blood flow, the marked increase in plasma gastrin, the significant fall in gastric somatostatin levels and Bcl-2 protein expression, and the rise in expression of COX-2 and Bax proteins. These mucosal changes were counteracted by the triple therapy and Lacidofil. CONCLUSIONS: H. pylori infection in gerbils, associated with regenerative hyperplasia of glandular structure, results in the suppression of gastric secretion, overexpression of COX-2, and enhancement in apoptosis and impairment of both, gastric blood flow and gastrin-somatostatin link that were reversed by anti-H. pylori triple therapy and attenuated by probiotics.

Amoxicillin↗
PubMed2006

The relationship between MSI status and vessel density in colorectal carcinoma.

The development of new blood vessels is a prerequisite for progression of malignant neoplasms. Factors that induce neoangiogenesis include VEGF, VEGF-C, VEGF-D, PD-ECG, ANG-2, TSP-1, HIF-1 and HIF-2. From the etiopathogenetic viewpoint, colorectal carcinoma is heterogenic. It may develop via a sequence of mutations leading to chromosome instability or else result from DNA repair defects, which are manifested as microsatellite instability. The objective of the present investigations was the comparison of neoangiogenesis in microsatellite-stable colorectal carcinomas, as well as in tumors with low and high instability levels. The material included 71 surgical cases of colorectal carcinoma. Vessel density was assessed by immunohistochemical reactions to CD34 and vWf, calculating the number of vessel sections within the invasion margin, in visual fields selected at random, and within hot spots. Microsatellite instability was evaluated in frozen materials employing the PCR reaction with gel and capillary electrophoresis. In all the cases, the authors detected CD34+ and less numerous vWf+ vessels within the tumor and in its vicinity. In 45 cases, no microsatellite instability was found, in 13 cases, low level instability (MSI-L) was observed, and in another 13 - high microsatellite instability (MSI-H). Some differences in vessel density were noted between the above groups, yet they were not statistically significant. On the other hand, the authors observed more numerous CD34+ vessels in cases with metastases to the regional lymph nodes. In conclusion, it is suggested that neoangiogenesis in sporadic colorectal carcinoma is directly related to metastatic potential, but not to MSI status.

Adenocarcinoma↗
PubMed2006

High thymidylate synthase expression is typical for sporadic MSI-H colorectal carcinoma.

Colorectal carcinoma is etiopathologically heterogenic. It may develop through a sequence of mutations leading to chromosome instability or be a result of defects in DNA repair mechanisms manifested by microsatellite instability. Carcinomas of this type are supposed to be characterized by a better prognosis and a different response to chemotherapy. The main target of 5-fluorouracil (5-FU) treatment is thymidylate synthase (TS). High TS expression has been identified as promoting resistance to 5-FU. The objective of the present investigation was to determine whether microsatellite instability is associated with thymidylate synthase expression. Ninety-eight cases of colorectal carcinoma were studied. Microsatellite instability was evaluated in frozen material employing the PCR reaction with gel and capillary electrophoresis. TS expression levels were assessed in preparations stained immunohistochemically using a semiquantitative method on a scale with scores from 0 to 3. The MSI-H phenotype was detected in ten cases, MSI-L in 16, and MSS in 72. The mean TS expression score was 1.79. In the MSS group, the mean TS expression score was 1.69, in the MSI-L group the mean TS expression score was 1.73, and in the MSI-H group the mean TS expression score was 2.67. The differences between MSI-H and MSS/MSI-L were statistically significant (p<0.0002 and p<0.004, respectively). The results may explain the different response of MSI-H carcinomas to 5-FU treatment.

Adenocarcinoma↗
PubMed2006

High prevalence of non-Hodgkin's lymphomas in Polish population--1106 new cases diagnosed according to WHO classification in only one district.

The authors present the true incidence of non-Hodgkin's lymphomas basing on the cases diagnosed in Małopolska district during one-year period. The data point to higher lymphoma morbidity than the incidence of them reported by National Cancer Register. Noteworthy is also the distribution of lymphoma types in Polish population being different from that one reported in majority of other Europe countries. The present report indicate the lymphomas become growing diagnostic and clinical challenge, as they place among the most frequent neoplasms in population.

Adolescent↗
PubMed2006

Tissue microarray FISH applied to colorectal carcinomas with various microsatellite status.

Colorectal carcinoma is etiopathologically heterogenic. It may develop through a sequence of mutations leading to chromosome instability or be a result of defects in DNA repair mechanisms manifested by microsatellite instability of varying degrees. Colorectal carcinoma can thus be classified into microsatellite-stable (MSS), highly microsatellite unstable (MSI-H) and intermediate low-level microsatellite unstable (MSI-L) groups. Fluorescent hybridization in situ (FISH) is a method of detecting specific sequences of nucleic acids that is based on specific bonding of a fluorescent marker-associated probe and specific DNA fragment. The material consisted of 146 non-selected cases of colorectal carcinoma patients operated on at First Chair of General Surgery, Collegium Medicum, Jagiellonian University in Cracow, Poland. Following a standard histopathological evaluation, tissue microarrays were prepared using a Tissue MicroArray Builder, and FISH was performed employing probes specific for chromosomes 1, 8, 17 and 18. Microsatellite instability was evaluated in frozen material using the PCR reaction with gel and capillary electrophoresis. The mean number of signals obtained for chromosome 1 in the entire material was 2.06, while the corresponding mean values in the MSS group equaled 2.07, in the MSI-L group - 2.07, and in the MSI-H group - 2.01. The mean number of signals for chromosome 17 in the entire material was 2.1, in the MSS group - 2.11, in the MSI-L group - 2.13, and in the MSI-H group - 2.01. The number of signals for chromosome 18 in the entire material was 2, in the MSS group - 2, in the MSI-L group - 2, and in the MSI-H group - 2. The means number of signals for chromosome 8 in the entire material was 2.07, in the MSS group - 2.08, in the MSI-L group - 2.01, and in the MSI-H group - 2. These differences are not sufficient for distinguishing colorectal carcinoma molecular forms.

Adenocarcinoma↗
PubMed2006

Correlation of microsatellite status, proliferation, apoptotic and selected immunohistochemical markers in colorectal carcinoma studied with tissue microarray.

Colorectal carcinoma is a frequent malignant tumor, characterized by varying clinical course and response to treatment. At the molecular level, colorectal carcinomas are divided into tumors with chromosomal instability (microsatellite-stable, MSS), microsatellite instability (MSI-H) and low microsatellite instability (MSI-L). The method of tissue microarrays allows for combining materials originating from multiple patients into a single slide, what makes possible to simultaneously investigate large material for the presence of numerous, diversified markers. The study material consisted of 208 cases of colorectal carcinoma. Microsatellite instability was evaluated in frozen material employing the PCR reaction with gel and capillary electrophoresis. Following a standard histopathological assessment, tissue microarrays were prepared using a MTA-1 microarrayer (Beecher) and standard immunohistochemical reactions were performed to detect the presence of bcl-2, CDX-2, Ki67, MLH1, MSH2, MSH6, p16, p53 and survivin. Apoptotic cells were detected using the TUNEL method. The correlations between the reactions were investigated and differences in the expression of the investigated proteins noted in carcinomas with various degrees of microsatellite instability. The agglomeration analysis showed differences in patterns of expression between MSS, MSI-L and MSI-H carcinomas. The discriminant function analysis demonstrated that the MSI-H carcinomas were best differentiated by MLH1, survivin and Ki67 expression, while the MSI-L tumors differed from the remaining colorectal carcinomas by their apoptotic index, local tumor stage (pT), the presence of angioinvasion and mucin production.

Adenocarcinoma↗
PubMed2005

Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis: involvement of cyclooxygenases and heat shock protein 70.

AIM: To determine whether ischemic preconditioning (IP) affects the development of edematous cerulein-induced pancreatitis and to assess the role of cyclooxygenase-1 (COX-1), COX-2, and heat shock protein 70 (HSP 70) in this process. METHODS: In male Wistar rats, IP was performed by clamping of celiac artery (twice for 5 min at 5-min intervals). Thirty minutes after IP or sham operation, acute pancreatitis was induced by cerulein. Activity of COX-1 or COX-2 was inhibited by resveratrol or rofecoxib, respectively (10 mg/kg). RESULTS: IP significantly reduced pancreatic damage in cerulein-induced pancreatitis as demonstrated by the improvement of pancreas histology, reduction in serum lipase and poly-C ribonuclease activity, and serum concentration of pro-inflammatory interleukin (IL)-1beta. Also, IP attenuated the pancreatitis-evoked fall in pancreatic blood flow and pancreatic DNA synthesis. Serum level of anti-inflammatory IL-10 was not affected by IP. Cerulein-induced pancreatitis and IP increased the content of HSP 70 in the pancreas. Maximal increase in HSP 70 was observed when IP was combined with cerulein-induced pancreatitis. Inhibition of COXs, especially COX-2, reduced the protective effect of IP in edematous pancreatitis. CONCLUSION: Our results indicate that IP reduces pancreatic damage in cerulein-induced pancreatitis and this effect, at least in part, depends on the activity of COXs and pancreatic production of HSP 70.

Animals↗
PubMed2005

Objective, planimetry-based assessment of megakaryocyte histological pictures in Philadelphia-chromosome-negative chronic myeloproliferative disorders: a perspective for a valuable adjunct diagnostic tool.

Philadelphia-chromosome-negative chronic myeloproliferative disorders (Ph- CMPDs)--essential thrombocythemia (ET), chronic idiopathic myelofibrosis (CIMF), and polycythemia vera (PV)--may show clinical and morphological similarities, particularly at the early stages. The differential diagnosis of Ph- CMPDs is important due to their different treatment and prognosis. Cytological features of megakaryocytes are considered valuable in this differentiation. To establish an objective measure of megakaryocyte dysplasia in Ph- CMPDs, we performed computer-assisted morphometry of more than 4,000 cells from 20 cases of ET, 10 of CIMF, 10 of PV, and 10 controls. Megakaryocyte sets from three Ph- CMPDs differed significantly in respect to many planimetric parameters, but not a single shape or size parameter could have been used as a discriminative tool between the entities. However, the discriminant function analysis with the simultaneous assessment of 12 planimetric variables allowed for a proper classification of 20 of 20 ET, 10 of 10 PV, and 9 of 10 CIMF cases based solely on the morphometric features of megakaryocytes. Additionally, we identified certain new patterns of megakaryocytes specific for ET, PV, and CIMF, which, although not dominating in one Ph- CMPD, are unlikely to occur in two others. Objective measurements of megakaryocyte sizes and shapes may assist the diagnosis of Ph- CMPDs.

Adult↗
PubMed2005

Biomarkers in various types of atrophic gastritis and their diagnostic usefulness.

Atrophic gastritis has been shown to involve either the oxyntic gland area, resulting in hypergastrinemia and hypopepsinogenemia I, the antral gland area, causing hypogastrinemia without change in serum pepsinogen I (diffuse antral gastritis; DAG), or the entire gastric mucosa (multifocal atrophic gastritis; MAG), resulting in both hypogastrinemia and hypopepsinogenemia I; and rare atrophic gastritis limited to the oxyntic gland area, with antibodies against oxyntic cells and/or intrinsic factor (autoimmune metaplastic atrophic gastritis; AMAG). This study was performed on 126 patients with various forms of gastritis and on 126 age- and gender-matched controls, who were subjected to endoscopy with biopsy, H. pylori testing (13C-UBT, serology), assays for serum gastrin and pepsinogen I, and testing for basal and pentagastrin-induced gastric acid secretion. The following groups of patients were examined: group I (N = 22), with AMAG; group II (N = 53), with DAG; group III (N = 51), with MAG; and group IV (N = 126), age- and gender-matched controls without gastritis. The following changes were found. In group I very high serum gastrin and very low pepsinogen I were observed, and all patients were achlorhydric and H. pylori negative. In group II, with low serum gastrin and normal pepsinogenemia and gastric chlorhydria, all patients were H. pylori positive. In group III, with lower serum gastrin and lower pepsinogen I levels and reduced chlorhydria, all patients were also H. pylori positive. And all group IV controls, with normal serum gastrin and pepsinogen I and normal gastric acid secretion without antral or fundic gastritis, were H. pylori negative. We conclude that measurements of serum gastrin and pepsinogen I and gastric acid secretion as well as testing for H. pylori infection may be useful in noninvasive diagnosis of various types of atrophic gastritis and in identification of patients with premalignant gastritis and a high risk of gastric cancerogenesis.

Adult↗
PubMed2005

Loss of heterozygosity on chromosome 22q in gastrointestinal stromal tumors (GISTs): a study on 50 cases.

Mutational activation of KIT or PDGFRA is considered an early step in pathogenesis of gastrointestinal stromal tumors (GISTs); however, other nonrandom genetic changes have also been identified. At least three common regions of deletions on chromosome 22q, which may harbor putative tumor suppressor genes, have been defined. However, mapping of these regions has been inconsistent. It has also been speculated that GI autonomous nerve tumors (GANTs), GISTs with ultrastructural features suggestive of autonomic nerve differentiation, are characterized by a specific deletion involving 22q13 cytogenetic region. This study was undertaken to evaluate loss of heterozygosity (LOH) on chromosome 22q in 50 GISTs, including 10 GANTs. Four tumors were incidental minimal lesions <or=10 mm in diameter. LOH was evaluated using 20 PCR-based microsatellite markers and capillary gel electrophoresis. In all, 15 (30%) cases showed LOH of more than 75% of informative markers, suggesting loss of chromosome 22q. A total of 24 GISTs (50%) revealed LOH of one to seven informative markers clustered in different loci suggesting simultaneous involvement of different regions. The highest frequency of LOH was seen at D22S922 and D22S425, mapped to 22q13.33 and 22q11.22, respectively. However, LOH at other regions including IL2RB and NF2 locus was also found. No NF2 mutations were identified in four analyzed tumors. LOH on chromosome 22q was more frequent among intestinal than among gastric GISTs; however, there was no difference between LOH pattern seen in tumors defined by different histologic, ultrastructural (GANT) and molecular features (KIT and PDGFRA mutations). Although minimal GISTs revealed LOH on chromosome 22q, there was a higher LOH frequency in malignant than in benign tumors. An isolated LOH at D22S425 was equally found in both benign and malignant tumors. These observations may suggest that LOHs on chromosome 22q in GISTs play a role in early stages of tumor formation as well as in late tumor progression.

Adult↗
PubMed2005

Influence of gastric colonization with Candida albicans on ulcer healing in rats: effect of ranitidine, aspirin and probiotic therapy.

OBJECTIVE: Candida albicans frequently inhabits the gastrointestinal tract of humans leading to gastrointestinal candidiasis, especially following suppression of gastric acidity, but studies on the relation between this fungal infection and gastric pathology are limited due to lack of convenient animal models resembling Candida infection in humans. MATERIAL AND METHODS. We compared the effects of C. albicans and vehicle inoculation on gastric secretion and healing of gastric ulcers induced by acetic acid in rats treated with 1) ranitidine (30 mg kg(-1) day(-1) s.c.) and 2) aspirin (ASA) (60 mg kg(-1) day(-1) i.g.) with or without probiotic bacteria Lactobacillus acidophillus. At day 0 and at 4, 15 and 25 days after ulcer induction, the ulcer area, the gastric blood flow (GBF), the quantitative gastric cultures of Candida and the expression of mRNAs for pro-inflammatory cytokines IL-1beta and TNF-alpha and growth factors EGF and TGFalpha were assessed in the gastric mucosa. RESULTS: Gastric acid output was reduced by over 40% soon after Candida inoculation and this effect persisted during all time intervals tested. The area of ulcers in control rats significantly decreased at day 15 and the ulcers disappeared almost completely after 25 days of their induction. In contrast, the ulcers were present until day 25 in Candida-inoculated rats followed by a fall in GBF and a rise in plasma gastrin levels, these effects being significantly attenuated by the co-treatment with Lactobacillus. Candidiasis was accompanied by up-regulation of mRNA for IL-1beta, TNF-alpha, EGF and TGFalpha and a significant increment in plasma IL-1beta and TNF-alpha levels. CONCLUSIONS: 1) Persistent colonization with Candida could be achieved in rats treated with antisecretory agents or non-steroidal anti-inflammatory drugs (NSAIDs) such as ASA; 2) candidiasis reduces gastric acid secretion, while delaying ulcer healing possibly due to the impairment in GBF in the ulcer area and enhanced expression and release of IL-1beta and TNFalpha and 3) probiotic therapy could be useful in the treatment against the deleterious action of fungal infection on the healing of pre-existing gastric ulcers.

Animals↗
PubMed2005

Multifocal atrophic gastritis: pathogenesis and therapeutic implications.

OBJECTIVE: This study, carried out on 51 patients with multifocal atrophic gastritis (MAG) and 92 age and sex-matched dyspeptic controls, was designed to examine both exocrine (gastric acid) and endocrine (gastrin) gastric secretion before and after therapeutic intervention including Helicobacter pylori eradication and vitamin C treatment. METHODS: Fasting and gastrin-releasing peptide-induced gastric acid secretion, serum levels of gastrin and proinflammatory (IL-1beta, IL-8, TNF-alpha) as well as gastric mucosal gene expression of ornithine decarboxylase (ODC), cyclooxygenase 2 (COX-2) and growth factors (epidermal growth factor and transforming growth factor alpha) were determined before and after the eradication of Helicobacter pylori and therapy with large doses (1 g/d) of vitamin C for 3 months. RESULTS: The H. pylori eradication, assessed by C-urea breath test, and vitamin C therapy failed to reverse the histological atrophy of the gastric mucosa but improved significantly the functional status of the atrophied mucosa, especially its exocrine and endocrine secretory activities, attenuated the expression of premalignant markers such as ODC and COX-2, raised the production of growth factors and diminished the release of proinflammatory cytokines. CONCLUSIONS: These results indicate that MAG may be considered as an environmental disease of the gastric mucosa, whose functional status can be improved by the eradication of H. pylori combined with antioxidant therapy with large doses of vitamin C.

Adult↗
PubMed2005

ALK-positive diffuse large B-cell lymphoma: two more cases and a brief literature review.

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare, recently defined tumor distinct in many aspects from ALK-positive anaplastic large cell lymphoma (ALCL). We present two additional cases of ALK+DLBCL recently diagnosed in our department and a review of literature. A 48-year old man presented with a large upper neck mass growing slowly over 18 months. Histologically the tumor was diagnosed as an ALK-positive diffuse large B-cell lymphoma. with plasmablastic features. Large, frequently intrasinusoidal tumor cells expressed CD138, EMA, weakly IgA and kappa, but were negative for other B-cell markers, T-cell markers and CD30. The ALK staining was cytoplasmic with the increased intensity in the Golgi area. At the diagnosis the patient manifested with the stage IIIB. Three courses of CHOP resulted in partial and only transient remission. The patient died of massive bleeding from his decomposing tumor 3 months after the diagnosis. A 49-year old man complaining of abdominal pain revealed abdominal lymphadenomegaly and a gastric infiltrate, involving the deep portions of the gastric wall. The tumor showed immunoblastic/anaplastic morphology, with some Reed-Sternberg-like cells positive for ALK. ALK immunostaining was cytoplasmic, weak in a routine immunostain, enhanced with double (proteinase + pressure cooker) antigen retrieval. FISH was consistent with the t(2;5)/nucleophosmin(NPM)-ALK rearrangement. The tumor demonstrated similar "null" B/T phenotype with positivity for IgA, lambda, EMA and LCA. The patient (stage IVB) currently undergoes chemotherapy. ALK-positive DLBCL affects mostly middle-aged men, shows generally poor but stage-dependent prognosis (at least 60% mortality rate), presents typically as a lymph node-based disseminated disease, and very rarely involves the bone marrow. Genetic studies showed that the majority of ALK+DLBCL cases are characterized by the clathrin (CLTC)-ALK fusion and in a few cases the NPM-ALK rearrangement has been found.

Anaplastic Lymphoma Kinase↗