Biomedical subjects

M A Piris

Publications and source records attributed to M A Piris.

At least 55 records · Page 3Linked to original sources

PubMed1998

Clinical outcome in diffuse large B-cell lymphoma is dependent on the relationship between different cell-cycle regulator proteins.

PURPOSE: The goal of this work was to perform a comprehensive exploration of the relationship between the clinical outcome of diffuse large B-cell lymphoma (DLBCL) and the expression of a panel of tumor suppressor and oncogenic proteins, which includes some cell-cycle regulator proteins involved in the p53 pathway. PATIENTS AND METHODS: To this end, we collected the clinical data of 141 patients with DLBCL and immunohistochemically analyzed diagnostic tumoral tissue from each patient for the presence of Ki67 (MIB1, Immuno-tech, Marseille, France), bcl2, p53, p21/WAF1, MDM2, and retinoblastoma (Rb) proteins. RESULTS: The results show that several proteins are associated with some of the clinical traits analyzed. Multivariate analysis showed that an extended overall survival (OS) time was associated with low growth fraction, high Rb protein, and low MDM2 expression, as well as with known clinical parameters. The probability of inducing a complete remission (CR) was only associated with clinical parameters, although univariate study showed that a low growth fraction was associated with a higher probability of inducing a CR. Univariate study of disease-free survival (DFS) showed that tumors with high bcl2 expression and nodal origin have a shorter DFS time, although multivariate study only confirmed the adverse effect of bcl2 expression. CONCLUSION: Taking all these results into consideration, it seems that although the overall outcome for patients with DLBCL is decided by a combination of different clinical and biologic variables, the expression of some of these cell-cycle regulator proteins appears to be specifically associated with the different clinical features of tumors.

Adolescent↗

PubMed1998

Absence of cyclin D1 protein expression in splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is a recently recognized primary splenic lymphoma. SMZL can be associated with peripheral lymphocytosis, in which some cells have a villous morphology (splenic lymphoma with villous lymphocytes [SLVL]). Several recent studies suggested involvement of the bcl-1 locus and/or the cyclin D1 gene, located on chromosome 11q, in SMZL/SLVL. Translocation t (11;14) is associated with rearrangement of the bcl-1 locus and overexpression of the cyclin D1 gene. Both the translocation and cyclin D1 protein expression are characteristic of mantle cell lymphoma (MCL) and are rare in other lymphoid neoplasms; thus, their detection is useful in the diagnosis of MCL. Because the differential diagnosis of low-grade lymphoma in the spleen can be difficult, it is important to assess the frequency of cyclin D1 expression in SMZL to determine its usefulness in differential diagnosis from MCL. We analyzed the expression of cyclin D1 nuclear protein in paraffin sections using an immunoperoxidase technique in 17 cases diagnosed as SMZL. In eight cases, the presence of cyclin D1 mRNA was also assessed by Northern blot analysis. None of the 17 cases of typical SMZL showed expression of cyclin D1 mRNA or protein. In contrast, four cases used as controls showed either expression of cyclin D1 protein or mRNA or both. We conclude that assessment of cyclin D1 protein expression can be useful in distinguishing SMZL from MCL involving the spleen.

Aged↗

PubMed1997

Adverse clinical outcome in Hodgkin's disease is associated with loss of retinoblastoma protein expression, high Ki67 proliferation index, and absence of Epstein-Barr virus-latent membrane protein 1 expression.

Previous studies have shown that in non-Hodgkin's lymphomas and others neoplasms, tumoral progression, treatment response, and outcome are related to the expression of different oncogenic and tumor suppressor proteins. This study aimed to determine the prognostic significance of the expression of p53, bcl2, retinoblastoma protein (Rb), Ki67, CD15, and latent membrane protein 1-Epstein-Barr Virus (LMP1-EBV) proteins in Hodgkin's disease. A retrospective study was performed on 140 patients collected at the 11 participating centers belonging to the Spanish Collaborative Group for the Study of Hodgkin's Disease. A highly sensitive immunohistochemical method with previous microwave-induced antigen retrieval technique was used for the demonstration of the above-mentioned proteins. A Cox's multivariate analysis was performed to evaluate the impact of the variables in the overall survival, together with a logistic regression model for the achievement of complete remission. Univariate statistical analysis confirmed the prognostic significance of the alredy known clinical parameters: stage, age over 60 years, and B symptoms. High proliferation index (Ki67) and loss of Rb expression were also found to be adverse prognostic factors influencing respectively lower overall survival and failure to achieve complete remission. Multivariate analysis confirmed the independent significance of these two parameters and additionally identifies LMP1-EBV expression as a favorable prognostic marker, in relation with overall survival. Histopathological type, p53, bcl2, and CD15 expression lack significant influence on the outcome of this series. The progression of the disease or the response to treatment in HD patients is the consequence of the interrelationship of different factors, among which LMP1 expression, loss of Rb, and high growth fraction seems to play a more relevant role.

Adolescent↗

PubMed1997

p21WAF1/CIP1 and MDM2 expression in non-Hodgkin's lymphoma and their relationship to p53 status: a p53+, MDM2-, p21-immunophenotype associated with missense p53 mutations.

p53 is a tumour suppressor gene which is often found to be inactivated in most types of human cancer. p53 is a transcription factor, the inactivation of which may lead to significant variations in the levels of p53 downstream proteins, such as p21WAF1/CIP1 and MDM2. In view of the significance of p21WAF1/CIP1 and MDM2 as wild-type (wt) p53 targets, this study was undertaken to monitor the varying expression of these proteins in non-Hodgkin's lymphomas (NHLs) in relation to p53 gene status. A total of 57 cases of different histological types of NHL were included in this study. Proteins p53, p21WAF1/CIP1, and MDM2 were analysed by immunohistochemical techniques, taking the levels expressed in reactive lymphoid tissues as reference points. p53 gene point mutations (exons 5-8) were looked for using the PCR-SSCP technique and direct sequencing. Fifteen of the 57 cases studied showed 16 mutations at the p53 gene: 12 missense, one nonsense, two silent mutations, and one frameshift deletion. Most missense mutations were associated with high levels of p53 protein, while the nonsense mutations and frameshift deletion did not induce detectable levels of p53. All cases with mutation at the p53 gene (15) showed null or low levels of p21WAF1/CIP1 and MDM2 proteins, suggesting that null or missense mutations at this gene give rise to a protein that is unable to transactivate the p21WAF1/CIP1 and MDM2 genes. The association between missense p53 mutation and dissociate immunophenotype (p53+, MDM2-, p21-) was statistically significant (Fisher's exact test, P = 0.0024). This anomalous p53+, MDM2-, p21- phenotype was also found in a small group of five cases with wt p53; this could indicate that in these cases p53 transactivation capacity has been abrogated by a mechanism other than p53 mutation. Most cases with the wt p53 gene show simultaneous immunohistochemical expression of all three proteins and often display higher levels than those found in reactive lymphoid tissue. There is a tendency for EBV-positive cases to harbour high levels of p53+ and p21+, suggesting that EBV could be involved in the nuclear accumulation of p53 and p21WAF1/CIP1 in NHL.

Cyclin-Dependent Kinase Inhibitor p21↗

PubMed1997

Aleukemic "leukemia cutis" of monocytic lineage.

We describe aleukemic leukemia cutis (ALC) in a 50-year-old woman who presented with numerous skin nodular lesions and lack of peripheral blood and bone marrow involvement until late in the evolution of her disease. We emphasize the value of immunohistochemical studies to distinguish ALC from cutaneous large cell lymphoma.

Diagnosis, Differential↗

PubMed1997

Frequent involvement of chromosomes 1, 3, 7 and 8 in splenic marginal zone B-cell lymphoma.

We have studied 19 cases of splenic marginal zone B-cell lymphoma (SMZBCL) combining cytological features, conventional cytogenetics, and in situ hybridization (ISH) techniques. A clonal chromosome abnormality was found in 11/19 patients (58%). The more frequent recurrent abnormalities were: del(3), del (7q), and involvement of chromosomes 1, 3, 7 and 8. No patient showed the translocation t(11;14)(q13;q32). An outstanding finding was the low incidence of trisomy 3 (36%) compared to patients with MALT lymphoma. These findings support the interpretation that SMZBCL is a distinct lymphoproliferative disorder.

Chromosome Aberrations↗

PubMed1997

p53 expression in CMV-infected cells: association with the alternative expression of the p53 transactivated genes p21/WAF1 and MDM2.

The p53 tumour suppressor gene is a cell cycle regulator, able to induce cell cycle arrest to allow DNA repair or apoptosis. The molecular mechanisms underlying p53 action imply transactivation of p53 dependent genes such as WAF1 (for wild type p53 associated fragment 1) and the murine double minute (MDM2) gene. In some cases, inactivation of the p53 gene results from p53 gene mutations leading to p53 protein accumulation, but in others it may results from mechanisms other than mutation, such as interaction with viral or cellular proteins. The expression of p53 protein and p53 transactivated gene proteins p21/WAF1 and MDM2, combined with in situ detection of apoptosis, was studied in specimens of CMV-infected patients as an in vivo model of p53 alteration not due to point mutation. p53 positivity was found in CMV + cells in different tissues, in cells with typical inclusion bodies, and in in situ hybridization and immunohistochemistry CMV + cells without inclusions (hidden infection). Although this p53 reactivity was accompanied by the expression of MDM2 and p21/WAF1 proteins, the patterns of MDM2 and p21/WAF1 protein expression were mutually exclusive, and were associated with the presence or absence of inclusion bodies. Nuclei bearing inclusion bodies were usually MDM2+, p21/ WAF1-, while hidden infected cells were usually MDM2-, p21/WAF1+. Apoptosis was not detected in any tissue section from CMV-infected patients. Two alternative patterns were found in CMV-infected tissues: p53+, p21/WAF1+, MDM2-, or p53+, p21/WAF1-. MDM2+ protein expression. These may represent examples of p53 dependent alternative effects in the course of CMV infection. Early stages are represented by CMV + cells without inclusion bodies, which display p53 and p21/ WAF1 expression, suggesting that p53 could be acting as a growth suppressor protein. Late CMV infection is represented by cells harbouring inclusion bodies. These cells showed a p53+, p21/WAF1-, MDM2+ profile, consistent with MDM2 mediated p53 inactivation. The absence of p21/WAF1 expression and lack of apoptosis suggest that the p53 protein expressed by MDM2+ cells could be functionally inactivated in CMV-infected cells with inclusion bodies. Previous studies have suggested that p53 inactivation by MDM2 over-expression occurs in sarcomas and lymphomas. Our observations seem to indicate that this mechanism of MDM2 mediated p53 inactivation may play a role in the late phase of CMV infection.

Adrenal Glands↗

PubMed1997

Lymph node involvement by splenic marginal zone lymphoma: morphological and immunohistochemical features.

Splenic marginal zone lymphoma (SMZL) has recently been proposed as a distinctive type of low-grade B-cell lymphoma. Although there is general agreement that this entity exists, its precise definition is blurred by uncertainty in differential diagnosis from other low-grade B-cell lymphomas. There is even more uncertainty as to the histology of splenic hilar and peripheral lymph nodes involved by SMZL. We therefore reviewed the histological and immunohistochemical features of 19 of these lymph nodes (14 hilar and five peripheral) from 14 cases of classical SMZL and compared them with the features of lymph nodes involved by other B-cell lymphomas. The morphology and immunohistology of the lymph nodes resemble those found in the white pulp of the spleen, showing a distinctive pattern, different from that which is observed in other B-cell lymphomas. In these cases, the overall architecture of the lymph nodes is effaced and replaced by a nodular infiltrate, although the sinuses are preserved in most hilar lymph nodes. Some of the nodules contain a central reactive follicular center, around which there is a broad zone of small lymphocytes. In other cases, the central area is partially infiltrated or, more commonly, totally replaced by these small lymphocytes, which in the periphery of the nodules showed a pale, slightly larger cytoplasm. Scattered nucleolated blasts are present, largely confined to the periphery of the nodules. The tumoral cells express immunoglobulin (Ig)D, IgM, and Ig light chain restriction and show a low proliferation fraction. These findings confirm that SMZL is a real entity, and not merely a morphological pattern of splenic infiltration by different types of low-grade B-cell lymphoma.

Adult↗

PubMed1997

Expression of p21WAF1/CIP1 in fetal and adult tissues: simultaneous analysis with Ki67 and p53.

AIMS: To determine the expression of p21WAF1/CIP1 in relation to the expression of Ki67 and p53 in various normal adult and fetal tissues, and to investigate its distribution throughout the cell cycle. METHODS: The expression of p21WAF1/CIP1 in relation to Ki67 and p53 was analysed in adult and fetal tissues using immunohistochemical techniques. Heat induced epitope retrieval techniques were used to characterise the presence of p21WAF1/CIP1 in different tissues, as well as to detect its distribution throughout the cell cycle. In addition, flow cytometry and western blotting were used to test whether the level of p21WAF1/CIP1 expression varied at different phases of the cell cycle in phytohaemagglutinin (PHA) stimulated lymphocytes. RESULTS: p21WAF1/CIP1 expression varied from one tissue to another, and it was restricted mainly to the squamous and glandular epithelium, where it appeared in association with p53. Human tissues in which p21WAF1/CIP1 was found showed a mutually exclusive topographical sequential expression between p21WAF1/CIP1 and Ki67. This was confirmed by double labelling studies, which showed that p21WAF1/CIP1 positive cells were in the G0 phase. Unlike these findings of a decline in p21WAF1/CIP1 expression after the G0 phase, PHA stimulated lymphocytes showed a level of p21WAF1/CIP1 expression that rose as the cell progressed through the cell cycle. CONCLUSIONS: The analysis of p21WAF1/CIP1 expression in relation to the status of p53 should take into account the existence of variable p21WAF1/CIP1 expression in different tissues. This could provide an explanation for the varying frequency of p53 mutations in tumours of different cellular origin. In tissues characterised by regular p21WAF1/CIP1 expression, it appears in a pattern that is consistent with the proposed role of this inhibitor of cyclin dependent kinases in cell cycle arrest-that of inducing cell differentiation. The conflicting results of in vivo and in vitro studies could support the hypothesis that microenvironmental conditions may influence the location of p21WAF1/CIP1 in different phases of the cell cycle.

Adult↗

PubMed1997

Cyclin-dependent kinase inhibitor p27KIP1 in lymphoid tissue: p27KIP1 expression is inversely proportional to the proliferative index.

Cell cycle progression is regulated by the combined action of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CDKIs). p27KIP1, which has a high degree of similarity with p21WAF1, is a general CDKI thought to be involved in G1 arrest in response to agents that inhibit cell cycle progression. The aims of this study were 1) to establish the pattern of expression of p27KIP1 protein in nontumor lymphoid tissue, 2) to determine whether p27KIP1 is involved in lymphomagenesis, and 3) to address the possible relationship between p27KIP1 and p21WAF1 expression in reactive and tumor lymphoid tissue. p27KIP1 protein was found to be mainly present in quiescent lymphocytes in reactive lymphoid tissue as well as in peripheral blood lymphocytes, with an inverse expression for p27KIP1 and Ki-67 proteins. The same p27KIP1 expression pattern was observed in lymphomas, independently of histological type; small resting cells were p27KIP1 positive, and large proliferating cells were p27KIP1 negative. Therefore, tumors with a low proliferative index were mostly positive, whereas tumors characterized by a higher growth fraction bad low p27KIP1 protein levels. An unexpected finding was the existence of a group of six cases of high-grade lymphomas (three diffuse large B-cell lymphomas and three Burkitt's lymphomas) with homogeneously strong staining for p27KIP1 protein. All 6 of these cases belong to a group of 28 cases characterized by blockage of the p53 tumor suppressor pathway, as determined by genetic (p53 mutation) or immunophenotypic studies (p53+/p21-). p27KIP1 expression was not seen in any case of aggressive non-Hodgkin's lymphoma with an intact p53 pathway. The results indicate that p27KIP1 is down-regulated in lymphomas with a high proliferative index, although it is highly expressed in high-grade lymphomas with defects in the p53 pathway.

Cell Cycle Proteins↗

PubMed1996

p53 gene mutations and protein overexpression are associated with aggressive variants of mantle cell lymphomas.

Mantle cell lymphoma (MCL) is molecularly characterized by bcl-1 rearrangement and cyclin D1/PRAD-1 gene overexpression. Some aggressive variants have been recognized with a blastic or large cell morphology, higher proliferative activity, and shorter survival. p53 gene mutations in lymphoid neoplasms have been detected mainly in high grade lymphomas and have been associated with tumor progression in follicular and small lymphocytic lymphomas. To determine the role of p53 alterations in MCL, we examined 35 typical and 8 aggressive variants (5 blastic and 3 large cell) of MCLs by a combination of immunohistochemistry, single-strand conformational polymorphism analysis of genomic DNA and/or cDNA obtained by reverse transcriptase-polymerase chain reaction, denaturing gradient gel electrophoresis, and sequencing. Of the 8 aggressive MCLs, 3 (38%) contained missense point mutations in axon 8 codon 278 (Pro --> Leu), exon 8 codon 273 Arg --> His), and exon 5 codon 151 (Pro --> Ser), respectively. A diffuse p53 protein overexpression was observed in more than 50% of the tumor cells in these 3 cases. A fourth blastic MCL also showed strong p53 immunoreactivity. However, no mutations were detected in exons 5-9 in this case. p53 expression was also detected in 10% of the cells in an additional large cell type of MCL and in less than 1% of the cells in 6 typical cases. No mutations were detected in any of these cases or in the remaining cases with no expression of the protein. Four nucleotide changes were observed by single-strand conformational polymorphism analysis in 4 typical MCLs with no overexpression of the protein. Direct sequencing showed that these nucleotide changes were located at exon 6 (1 case), intron 7 (2 cases), and intron 8 (1 case). The changes in exon 6 and intron 7 were known polymorphisms. The nucleotide change in intron 8 was outside splicing sites of the neighboring exons. The overall survival of the 3 patients with p53 mutations (median, 18.3 months) was significantly shorter than that of patients with the nonmutated MCLs (median, 49 months; P < .01). These findings indicate that p53 gene mutations are an infrequent phenomenon in MCLs and are associated with a subset of aggressive variants.

Base Sequence↗

PubMed1996

MDM2 and p21WAF1/CIP1, wild-type p53-induced proteins, are regularly expressed by Sternberg-Reed cells in Hodgkin's disease.

Mutations in the p53 tumour suppressor gene are the most common genetic alteration found in human cancers. Most of them are accompanied by stabilization of the protein, which renders it detectable through immunohistochemical techniques. Although p53 expression is a very common finding in Hodgkin's disease (HD), the status of the p53 gene is scarcely known, due to the difficulty in sequencing this gene in a lesion in which tumour cells are thought to constitute a very minor subpopulation, diluted in a background of supposedly benign cells. The pattern of expression of two downstream p53 proteins (MDM2 and p21 WAF1/CIP1, was studied as an indirect way of assessing p53 gene status. MDM2 is a wild-p53 inducible protein which may form a complex with p53, abrogating its function, as has been found in human sarcomas and other malignancies. p21WAF1/CIP1 is another protein inducible by wild-type p53, involved in inhibiting cell-cycle progression, through binding to cyclin/cyclin-dependent-kinase complexes. MDM2 and p21WAF1/CIP1 immunostaining was detected in all the cases analysed, independently of histological type, and were mainly present in Sternberg-Reed and Hodgkin (H & SR) cells. These immunohistochemical results were confirmed by Western blotting. To study the cause of MDM2 protein accumulation, MDM2 mRNA expression was also investigated by reverse transcription polymerase chain reaction (RT-PCR). The results show the presence of MDM2 transcripts in all cases of HD, albeit at lower levels than those found in reactive lymphoid tissue. These results seem to support the hypothesis that p53 is transcriptionally active in at least some of the H & SR cells in HD, and is able to induce MDM2 and p21WAF1/CIP1 protein expression.

Blotting, Western↗

PubMed1996

Anomalous retinoblastoma protein expression in Sternberg-Reed cells in Hodgkin's disease: a comparative study with p53 and Ki67 expression.

Retinoblastoma (Rb) tumour-suppressor protein plays a critical role in cell cycle control. Rb inactivation is a frequent phenomenon in tumours of different cell lineages, in which the absence of Rb protein has been considered to be a marker of Rb disregulation. We used modern immunohistochemical techniques to study the expression of Rb protein in a large series of 130 patients with Hodgkin's disease. Simultaneously, Western blot was used to analyse a more restricted group (12 patients) to confirm the immunohistochemical results and to clarify the phosphorylation status of Rb protein. As the level of Rb expression varied according to cell cycle stage, we also performed immunostaining for Ki67, a protein present in proliferating cells. To make comparison possible, we first characterised the amount and phosphorylation status of Rb protein in reactive lymphoid tissue and phytohaemagglutinin (PHA)-stimulated lymphocytes. The presence of p53 in Sternberg-Reed cells was also included in the study, as both proteins (p53 and Rb) have been found to be closely associated in cell cycle control. PHA-stimulated peripheral blood lymphocytes showed a parallel increase in Rb and cell cycle progression, together with progressive Rb phosphorylation. In reactive lymphoid tissue there was also a clear correlation between Rb expression and the Ki67 proliferation index (R = 0.96, P = 0.038). When analysing Hodgkin's disease samples, a clear difference emerges between cases of nodular lymphocyte predominance, which preserve the relationship between Rb and Ki67 expression (r = 0.8727, P = 0.000), and classical forms of Hodgkin's disease (nodular sclerosis and mixed cellularity), which display a strong deviation from this pattern. Two main anomalies were found: (1) One group of 21/130 cases with partial or total loss of Rb protein expression, which could reflect the existence of genetic alterations, or an altered transcriptional or translational regulation of Rb gene. (2) Another group with an abnormally high Rb/Ki67 ratio, which could support conflicting interpretations: (i) excess Rb protein for controlling cell cycle progression; or (ii) adhesion of Rb protein to other cellular or viral proteins, such as p53 and MDM2. The results of this study indicate an anomalous pattern of expression of Rb in classical forms of Hodgkin's disease, and suggest the possibility of undertaking functional studies (E1A adhesion, p16 expression) with the aim of better characterising the status of Rb protein, and correlating these findings with clinical course in Hodgkin's disease patients.

Hodgkin Disease↗

PubMed1996

EBV-positive non-Hodgkin's lymphoma developing after phenytoin therapy.

We report the first case of Epstein Barr virus (EBV) positive non-Hodgkin's lymphoma occurring 20 years after continuous phenytoin therapy for idiopathic epilepsy. This malignant lymphoproliferative disease was preceded by an phenytoin-associated benign reactive lymphadenopathy. Serological findings suggested a chronic active EBV infection. Immunohistochemistry showed that neoplastic cells expressed B antigens (CD20, lambda) and the bcl-2 protein. The presence of EBV-encoded latent membrane protein 1 (LMP 1) was also expressed on neoplastic cells. Cytotoxic chemotherapy (CHOP) reversed the non-Hodgkin's lymphoma.

Anticonvulsants↗

PubMed1996

Detection of the bcl-1 rearrangement at the major translocation cluster in frozen and paraffin-embedded tissues of mantle cell lymphomas by polymerase chain reaction.

The t(11;14)(q13;q32) translocation and its molecular counterpart bcl-1 rearrangement are highly characteristic of mantle cell lymphomas (MCLs). Most of these translocations occur at the major translocation cluster (MTC) in a tight area that makes this rearrangement identifiable by the polymerase chain reaction (PCR). In this study, the specificity and sensitivity of the PCR technique in the identification of bcl-1 rearrangement and its suitability to amplify the t(11;14) MTC in fixed, paraffin-embedded tissues were analyzed. Genomic DNA was obtained from 21 MCLs and 1 chronic lymphocytic leukemia (CLL) with the t(11;14) translocation. The bcl-1 rearrangement was studied by Southern blot with the MTC, p94PS, and PRAD-1 probes. Polymerase chain reaction was performed using a JH consensus primer and specific primers for chromosome II in the MTC region. bcl-1 rearrangement was identified by Southern blot in the MTC in nine (43%) MCLs and in the p94PS region in the CLL. Polymerase chain reaction analysis of genomic DNA showed that the nine MCLs with MTC rearrangement also had an amplifiable band of the expected size (100%). No amplifiable products were detected in the negative MCLs or in the CLL. The specificity of the PCR products was confirmed by hybridization with an internal MTC oligonucleotide probe. Amplifiable DNA was obtained from the paraffin blocks of 7 cases with MTC rearrangement and 11 negative tumors. bcl-1 rearrangement was detected in this DNA of 6 positive MCLs (86%) by PCR and in none of the negative cases. In conclusion, this study demonstrates that the PCR technique is highly sensitive and specific for the detection of the bcl-1 rearrangement at the MTC. It can be used with both high molecular weight DNA and DNA obtained from formalin-fixed, paraffin-embedded tissues.

Base Sequence↗

PubMed1996

True histiocytic lymphoma of the stomach associated with low-grade B-cell mucosa-associated lymphoid tissue (MALT)-type lymphoma.

True histiocytic lymphoma is considered a rare entity, and its diagnosis requires the concordance of morphological, immunophenotypic, and molecular findings. The association of malignant lymphoma with tumors in the monocyte-macrophage system has rarely been described. We present a case of mucosa-associated lymphoid tissue (MALT)-type low-grade B-cell lymphoma of the stomach, contiguous to a large tumoral mass that fulfills the morphological criteria (large cells with abundant pale cytoplasm and lobulated or kidney-shaped nuclei) and immunophenotypical features (human leukocyte antigen-DR locus, CD68, S-100, lysozyme immunoreactivity, and negative B- and T-cell markers) required for the diagnosis of histiocytic lymphoma. The patient remains in complete remission 18 months after surgery. The association of low grade-malignant lymphoma with tumors of monocyte-macrophage system cells is an exceedingly rare phenomenon. Whether these tumors are directly related or occur due to pure chance requires the identification of new cases and further study.

Antibodies↗

PubMed1996

Evaluation of the international index in the prognosis of high grade gastric malt lymphoma.

The International Prognostic Index identifies four risk groups with different survival rates in aggressive non-Hodgkin's lymphoma. We have studied whether a slight modification of this index has prognostic significance in high grade gastric B-cell MALT lymphoma. In 53 patients with high grade gastric B-cell MALT lymphoma the following survival factors were investigated: age over or under 60 years, sex, B symptoms, more than one extranodal site of involvement other than the stomach, serum LDH levels, performance status, stage I/IIE1/IIE2 v.s. stage III/IV, treatment with surgery, chemotherapy or both modalities together and the four risk groups as defined by the Modified International Prognostic Index (MIPI). A multivariate Cox's test was used to evaluate the independent prognostic significance on survival of all the above variables. Advanced stage (III/IV) and involvement of more than one extranodal site not including stomach were the only variables influencing survival. The MIPI was not sufficient to separate groups with significant differences in survival or to stratify prognostic groups. In this series, the MIPI did not show prognostic significance in high grade gastric B-cell MALT lymphoma.

Adolescent↗

PubMed1996

Expression of retinoblastoma gene product (pRb) in mantle cell lymphomas. Correlation with cyclin D1 (PRAD1/CCND1) mRNA levels and proliferative activity.

Mantle cell lymphomas (MCLs) are molecularly characterized by bcl-1 rearrangement and constant cyclin D1 (PRAD-1/CCND1) gene overexpression. Cyclin D1 is a G1 cyclin that participates in the control of the cell cycle progression by interacting with the retinoblastoma gene product (pRb). Inactivation of the Rb tumor suppressor gene has been implicated in the development of different types of human tumors including some high grade non-Hodgkin's lymphomas. To determine the role of the retinoblastoma gene in the pathogenesis of MCLs and its possible interaction with cyclin D1, pRb expression was examined in 23 MCLs including 17 typical and 6 blastic variants by immunohistochemistry and Western blot. Rb gene structure was studied in 13 cases by Southern blot. Cytogenetic analysis was performed in 5 cases. The results were compared with the cyclin D1 mRNA levels examined by Northern analysis, and the proliferative activity of the tumors was measured by Ki-67 growth fraction and flow cytometry. pRb was expressed in all MCLs. The expression varied from case to case (mean, 14.1% of positive cells; range, 1.3 to 42%) with a significant correlation with the proliferative activity of the tumors (mitotic index r = 0.85; Ki-67 r = 0.7; S phase = 0.73). Blastic variants showed higher numbers of pRb-positive cells (mean, 29%) than the typical cases (10%; P < 0.005) by immunohistochemistry and, concordantly, higher levels of expression by Western blot. In addition, the blastic cases also had an increased expression of the phosphorylated protein. No alterations in Rb gene structure were observed by Southern blot analysis. Cyclin D1 mRNA levels were independent of pRb expression and the proliferative activity of the tumors. These findings suggest that pRb in MCLs is normally regulated in relation to the proliferative activity of the tumors. Cyclin D1 overexpression may play a role in the maintenance of cell proliferation by overcoming the suppressive growth control of pRb.

Aged↗