Biomedical subjects

J Diebold

Publications and source records attributed to J Diebold.

At least 37 records · Page 2Linked to original sources

PubMed2002

Peripheral T-cell lymphoma (excluding anaplastic large-cell lymphoma): results from the Non-Hodgkin's Lymphoma Classification Project.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is rare in most parts of the world. Therefore, we have evaluated the 96 cases of PTCL diagnosed within the Non-Hodgkin's Lymphoma Classification Project (NHLCP) (1378 cases) for their geographical distribution, pathologic features and diagnostic reliability, as well as clinical presentation and outcome. MATERIALS AND METHODS: Diagnoses of all cases were rendered independently by five experienced hematopathologists based on morphology only, and after introduction of the immunophenotype and clinical data. Divergent diagnoses were jointly discussed and a final consensus diagnosis was established in each case. Reliability of the diagnoses was evaluated statistically, and the clinical features and outcome were analyzed according to the consensus diagnoses. RESULTS: Seven per cent of all non-Hodgkin's lymphoma (NHL) cases reviewed were classified as PTCL and the frequency varied from 1.5% to 18.3% in different countries. The interobserver agreement with the consensus diagnosis of PTCL was 86% in the Revised European-American Lymphoma (REAL) classification, but the designation of subtypes was less reliable. Diagnostic reliability improved from 41% to 86% after immunophenotyping, but did not improve further with the addition of detailed clinical data. Clinically, angiocentric nasal lymphoma presented in young females (median age 49 years) at extranodal sites, but with few adverse risk factors, whereas angioimmunoblastic lymphoma presented most often in older males (median age 65 years) at nodal and extranodal sites with numerous risk factors. The 5-year overall and failure-free survivals for patients with PTCL treated with doxorubicin (Adriamycin)-containing regimens were only 26% and 20%, respectively. Both failure-free and overall survival were strongly correlated with the performance status and International Prognostic Index scores at presentation, but differences in survival were not observed between the major histological types. However, within the PTCL 'not otherwise specified' category, but not angioimmunoblastic lymphoma, the number of transformed blasts was prognostically relevant. CONCLUSIONS: PTCLs can be diagnosed reliably by experienced hematopathologists, but immunophenotyping is absolutely necessary. Currently, all types of PTCL should be considered high-grade lymphomas. An increased ability to distinguish T-lymphocyte subsets is needed in order to better subclassify the PTCLs for therapeutic and prognostic purposes.

Adolescent↗

PubMed2002

Characteristic pattern of genetic aberrations in ovarian granulosa cell tumors.

The cytogenetic abnormalities of granulosa cell tumors (GCT) of the ovary are only partially known. Up to now, mainly numerical chromosomal aberrations have been described. Therefore we performed a comprehensive study on paraffin-embedded material of 20 GCT (17 adult, 3 juvenile; patient age between 16 and 78 y) combining comparative genomic hybridization (CGH); fluorescence in situ hybridization (FISH) using DNA-specific probes for chromosome 12, 17, 22, and X; DNA cytometry; and immunohistochemistry (inhibin, p53, Ki67). By DNA cytometry, 16 of 20 tumors (80%) were diploid. However, 6 of 16 diploid tumors (37%) showed aberrations by FISH. FISH revealed monosomy 22 in 8/18 cases (40%); trisomy 12 in 5/20 (25%); monosomy X in 2/20 (10%); and loss of chromosome 17 in one case (5%). The main findings by CGH were gains of chromosomes 12 (6 cases, 33%) and 14 (6 cases, 33%) and losses of chromosomes 22 (7 cases, 35%) and X (1 case, 5%), mostly comprising whole chromosomes or chromosome arms. Inhibin and p53 were expressed in 100% and 95% of the tumors, respectively. The Ki67 index ranged from 0% to 61%. Neither immunohistochemistry, nor DNA cytometry and molecular genetic analysis, provided statistically significant prognostic information. In summary, our study reveals a distinctive pattern of cytogenetic alterations in GCT. Our observations confirm earlier reports that trisomy 12 and 14 are frequent aberrations; however, monosomy 22 seemingly is even more prevalent.

Adolescent↗

PubMed2001

Systemic anaplastic large-cell lymphoma: results from the non-Hodgkin's lymphoma classification project.

Anaplastic large-cell lymphoma (ALCL) is a heterogeneous process that may have a T-cell, B-cell, or indeterminant (null) phenotype and which may or may not express the anaplastic lymphoma kinase (ALK) oncoprotein. Because the clinical significance of these variants of ALCL is unclear, we evaluated the cases of ALCL-T/null and ALCL-B identified in the Non-Hodgkin's Lymphoma Classification Project. We evaluated 1,378 cases of non-Hodgkin's lymphoma (NHL), and a consensus diagnosis of ALCL-T/null was made in 33 patients (2.4%) with a diagnostic accuracy of 85%. Compared to 96 patients with other forms of peripheral T-cell lymphoma (PTCL), those with ALCL-T/null were significantly younger, less likely to have advanced-stage disease or bone marrow involvement, more likely to have a low International Prognostic Index score, and had a significantly better survival. Among those with ALCL-T/null, there were no significant differences in the clinical features or survival on the basis of ALK expression. A consensus diagnosis of ALCL-B was made in 15 patients (1.1%), and the diagnostic accuracy was 67%. However, compared to 366 patients with other forms of diffuse large B-cell lymphoma (DLBCL), those with ALCL-B were no different with regard to clinical features or survival. We conclude that patients with ALCL-T/null have favorable prognostic features and excellent survival and should be separated from those with other forms of PTCL for prognostic and therapeutic purposes. In contrast, patients with ALCL-B appear to be similar to those with other forms of DLBCL.

Adult↗

PubMed2001

Prognostic relevance of hMLH1, hMSH2, and BAX protein expression in endometrial carcinoma.

Endometrial carcinoma is the most common gynecologic malignancy in perimenopausal and postmenopausal women. A role of mismatch repair genes, like hMLH1 and hMSH2 in their pathogenesis, has been suggested. Loss of their function leads to the accumulation of replication errors (mutator phenotype), which are responsible for further mutations in genes with microsatellite sequences in their coding region, such as Bax. We analyzed the expression of hMLH1, hMSH2, and Bax genes in 89 formalin-fixed paraffin-embedded endometrial carcinomas. The immunostains were scored with regard to percentage of positive tumor cells (0%, <10%, 10 to 50%, >50%), and relative staining intensity (1+, 2+, 3+). The staining results were correlated with clinicopathologic features and survival. Loss of hMSH2 expression (0% positive cells) was observed in 1.1% (1/89) of the tumors; loss of hMLH1 was seen in 12.4% (11/89) of the cases, particularly in endometrioid tumors with mucinous differentation (5/11; 45%; P =.03). No significant association was found between the immunoscores and grade, stage criteria of the International Federation of Obstetrics and Gynecology (FIGO), or age of the patients. Among 11 tumors with loss of Bax expression (12.4%), 4 had also loss of hMLH1 (4/11; 36.4%; P =.017). In multivariate analysis (Cox model), significantly longer survival was found for patients with tumors in FIGO Stage I-II (P <.0001), endometrioid type (P =.001), low grade (P =.001), and absence of hMLH1 expression (P =.027). Our results suggest that loss of function of hMLH1 and Bax occur in a subgroup of endometrial carcinoma. In addition to the classical prognostic factors, absence of hMLH1 expression is associated with better outcome of patients.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Synchronous pulmonary adenocarcinoma and extranodal marginal zone/low-grade B-cell lymphoma of MALT type.

A case of synchronous adenocarcinoma of lung and extranodal marginal zone/low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is reported. Primary pulmonary non-Hodgkin's lymphoma is relatively rare, however, the majority of these lesions are low-grade B-cell lymphomas of MALT. After the stomach, the lung is the second most common location for such latter lesions. Lung adenocarcinoma in selected countries is fast becoming the leading form of non small-cell lung carcinoma. To our knowledge, this synchronous occurrence in the lung has not been previously reported. Such associations have been primarily limited to gastric lesions where an association with Helicobacter pylori infection has been identified. This case report highlights the importance of adjunctive diagnostic investigations such as molecular techniques in conclusive analysis of synchronous cases such as ours.

Adenocarcinoma↗

PubMed2001

[Dyspnea caused by leiomyomatous tumor of the oropharynx].

BACKGROUND: Leiomyoma and Leiomyosarkoma are not often found in ENT-diseases. PATIENTS: We report on a 62-year old female patient presenting with a 3 x 4 cm tumor in the oropharynx that had developed within a period of about three weeks. The patient complained of increasing dysphagia and dyspnea especially when lying on the left side. To secure breathing the patient had to be primarily ventilated by placing a needle percutaneously through the conical ligament and was then intubated. For this procedure the patient was positioned on the right side. The tumor measuring 3 cm, was removed surgically. RESULTS: The tumor turned out to be a leiomyomatous neoplasia of undetermined malignant potential. Since an unfavourable behaviour of such neoplasms cannot be excluded, patients with tumors of this type should be followed closely. CONCLUSIONS: In this case the tumor leads to an acute dyspnoea and a special procedure of anesthesia was necessary. Therapeutic considerations and differential diagnosis of this very rare tumor of the oropharynx are discussed by reviewing the literature.

Deglutition Disorders↗

PubMed2001

Pathologic and clinical features of 77 Hodgkin's lymphoma patients treated in a lymphoma protocol (LNH87): a GELA study.

Between 1987 and 1993, 77 of 2855 lymphomas included in the LNH87 protocol of the GELA as non-Hodgkin lymphoma (NHL) and reviewed by a panel of pathologists had a diagnosis changed to Hodgkin lymphoma (HL). Some of these lymphomas had been initially interpreted as anaplastic large-cell lymphoma Hodgkin-like (ALCL-HL subtype). The purpose of this study was to analyze the histologic pitfalls initially encountered, to define more clearly the diagnostic criteria of lymphomas placed in the gray zone around HL, and to follow the survival of these 77 patients affected with HL and initially treated with NHL regimens. The 77 cases of HL were reviewed by three hematopathologists and immunostained with a large panel of antibodies, including CD30, CD15, CD3, CD20, CD45, CD43, LMP-1, EMA, BNH-9, TiA1, and ALK1. Each case was classified according to the Lukes-Rye system and the British National Lymphoma Investigation (BNLI) grading. The initial clinical presentation of patients was analyzed, and the overall and event-free survival rates of the 77 patients were estimated. Among the 77 HLs, 46 were misinterpreted as NHL by primary individual pathologists (12 as ALCL, 8 as ALCL-HL, 12 as peripheral T-cell lymphoma (PTCL), 6 as B-cell lymphoma, and 8 as unclassifiable NHL). The other 31 cases had been first considered by the panel as consistent with ALCL-HL (n = 18) or with PTCL (n = 13) and were changed later in view of an immunophenotype concordant with HL. Fifty-five percent of the patients completed the full NHL treatment. The 5-year event-free and overall survival rates were 54% and 77%, respectively. The current results indicate that lymphomas initially called ALCL-HL should not be regarded as a variant of ALCL, but as HL. The clinical consequences of misdiagnoses seem to be a lower event-free survival rate compared with that of classical HL, probably because of more relapses of initially inappropriately treated HL.

Adolescent↗

PubMed2001

Cellular apoptosis susceptibility gene expression in endometrial carcinoma: correlation with Bcl-2, Bax, and caspase-3 expression and outcome.

Deregulation of proliferation and apoptosis is known to contribute to neoplastic transformation and growth. Using specific antibodies for the cellular apoptosis susceptibility (CAS) gene, caspase-3, Bcl-2, and Bax, we examined the protein expression in 89 endometrial carcinomas and in 56 samples of nonneoplastic adjacent endometrium for comparison. Immunostaining results were scored with regard to approximate percentage of positive tumor cells (< 10%, 10% to 50%, > 50%) and relative immunostaining intensity (1+, 2+, 3+). In nonneoplastic endometrium, CAS protein was expressed in 70.6%, Bax in 64%, caspase-3 in 52%, and Bcl-2 in 87%. In neoplastic tissue, CAS was present in 93% of the tumors, Bax in 88%, caspase-3 in 77%, and Bcl-2 in 51%. Bcl-2:Bax ratio was > 1 in 9 cases (10%). In cases of atrophy (n = 24) and simple (n = 10) and complex (n = 22) hyperplasia in the adjacent endometrium, lower levels of expression compared with carcinoma were observed for CAS (p = 0.003), caspase-3 (p = 0.034), and Bax (p = 0.04) and higher levels for Bcl-2, although for this protein the results were not statistically significant (p = 0.32). There was no association between immunoscores and FIGO stage. High caspase-3 levels were seen in endometrioid tumor type (p = 0.017). CAS expression was higher in grade 3 tumors (p = 0.002) and older patients (p = 0.013). All tumors of younger patients (< 50 years) were Bcl-2 negative (p = 0.037). Caspase-3 correlated positively with CAS (p = 0.008), Bax (p = 0.04), and low Bcl-2:Bax ratio (p = 0.043), and inversely (as a trend) with Bcl-2 (p = 0.056). Survival analysis (Kaplan-Meier and Cox regression) established a strong association between prognosis and stage, grade, and histologic type (all p < or = 0.0036). In addition, shorter survival was observed for patients whose tumors contained > 50% of positive cells for caspase-3 (p = 0.024) or for CAS (p = 0.04). Age, Bcl-2, Bax, and Bcl-2:Bax ratio did not provide prognostic information. Our results suggest a role of CAS, Bcl-2, Bax, and caspase-3, which are apparently involved in the progressive deregulation of proliferation and apoptosis leading from simple and complex hyperplasia to carcinoma. In addition, CAS and caspase-3 protein levels may be useful markers in predicting the outcome of the patients.

Adenocarcinoma, Mucinous↗

PubMed2001

[Cutaneous manifestations of B-CLL masked by florid epithelioid granulomatous response].

We report an unusual case of iterative cutaneous manifestations of B-cell chronic lymphocytic leukaemia, masked by a florid epithelioid granulomatous response. These cutaneous lesions appeared without blood hyperlymphocytosis or lymph node enlargement. The diagnosis of cutaneous tumorous infiltrates was morphologically very difficult and required immunohistochemistry as well as PCR. This observation stresses the diagnostic difficulties encountered in lymphoma, with intense stroma reaction and the need for complementary techniques to reach the right diagnosis and thus deliver appropriate therapy.

Aged↗

PubMed2001

[Phenotype--genotype--correlation in ovarian neoplasia].

Ovarian neoplasms display a wide range of phenotypic differentiation patterns. In the recent past, molecular genetic aberrations have been increasingly identified in various types of ovarian tumors. Granulosa cell tumors most often contain numeric chromosomal aberrations (monosomy 22, trisomy 12 and 14). Numeric changes can also be found in benign and borderline epithelial neoplasms, however without demonstrating specific patterns. K-ras mutations are characteristic for mucinous ovarian tumors and for serous borderline (LMP) tumors. In serous LMP tumors they are associated with low level microsatellite instability. Complex chromosomal aberrations are not detected in benign and borderline tumors. Invasive ovarian carcinomas show complex genetic changes. Chromosomal gains at 3q26, 8q24 and 20q13 apparently represent early lesions, whereas loss of material of chromosomes 4, 13, 16, 18 and X is associated with tumor progression and poor prognosis. The main targets of chromosomal changes are regulatory genes of cell proliferation and apoptosis (e.g. p16, cyclin D1, Rb, p53, myc, bcl-2) and members of the signaling cascade of tyrosine kinase receptors (e.g. Her-2/neu, dab-2, K-ras, PI3-K, PTEN). The genetic alterations of ovarian neoplasms described so far apparently correlate with the different level of aggressiveness. However, they do not fully explain the spectrum of phenotypic variability of these tumors.

Apoptosis↗

PubMed2000

Prognostic significance of survivin expression in diffuse large B-cell lymphomas.

Survivin is an inhibitor of apoptosis overexpressed in various human cancers but undetectable in normal differentiated tissues. A potential expression and prognostic significance of survivin was studied in 222 patients with diffuse large B-cell lymphomas (centroblastic, 96%; immunoblastic, 4%). All patients were enrolled between 1987 and 1993 (median follow-up, 7 years) in the LNH87 protocol of the Groupe d'Etudes des Lymphomes de l'Adulte (GELA) and treated either with the reference ACVBP arm (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone)[AU3A] (n = 79) or other experimental anthracycline-containing regimens (n = 143). The characteristics of these patients were median age of 56 years; serum lactate dehydrogenase (LDH) greater than 1N, 60%; stage III-IV, 55%; performance status, according to the Eastern Cooperative Oncology Group (ECOG) scale, more than 1, 23%; extranodal sites more than 1, 29%; mass more than 10 cm, 44%; bone marrow involvement, 15%. Of the 222 patients studied, 134 (60%) revealed survivin expression in virtually all tumor cells by immunohistochemistry. The overall 5-year survival rate was significantly lower in patients with survivin expression than in those without (40% vs 54%, P =.02). Multivariate analysis incorporating prognostic factors from the International Prognostic Index (IPI) identified survivin expression as an independent predictive parameter on survival (P =.03, relative risk [RR] = 1.6) in addition to LDH (P =.02, RR = 1.6), stage (P =.03, RR = 1.7), and ECOG scale (P =.05, RR = 1.6). A second analysis incorporating IPI as a unique parameter demonstrated that survivin expression (P =.02, RR = 1.6) remained a prognostic factor for survival independently of IPI (P =.001, RR = 1.5). Survivin expression may be considered a new unfavorable prognostic factor of diffuse large B-cell lymphoma. (Blood. 2000;96:1921-1925)

Adolescent↗

PubMed2000

Photodetection of cervical intraepithelial neoplasia using 5-aminolevulinic acid-induced porphyrin fluorescence.

BACKGROUND: Screening for cervical carcinoma and its precursors is based on cervical cytology and diagnostic colposcopy. Despite the decrease in the incidence of cervical carcinoma in countries with a good screening program, this rate of decline is leveling off. Known problems are false-negative rates of cytology and low specificity of colposcopy. This clinical study examined the diagnostic potential of porphyrin fluorescence in patients with cervical intraepithelial neoplasia Grade 1-3 (CIN 1-3). METHODS: Sixty-eight women attending our colposcopy clinic underwent a gynecologic examination, including cytology, human papillomavirus (HPV) testing, and colposcopy. They received 10 mL 0.5% or 1.0% 5-aminolevulinic acid (5-ALA) topically. After 30-360 minutes, real-time image analysis was performed, and spectra were obtained from 685 sites. RESULTS: Due to rapid photobleaching, 0.5% 5-ALA proved ineffective for fluorescence assessment. Using 1% 5-ALA, the authors found that fluorescence intensities correlated with incubation time; however, fluorescence contrast showed a maximum at 60-90 minutes (ratio 11:1). HPV DNA positive lesions showed significantly higher fluorescence. Fluorescence imaging after 60-90 minutes achieved similar sensitivity and specificity compared with colposcopy in detecting CIN with 94% and 51% versus 95% and 50%, respectively. However, the specificity was markedly improved by fluorescence spectroscopy, achieving 75%. The evaluation of spectral measurements revealed significantly higher values for CIN compared with normal tissue and for CIN 2/3 compared with CIN 1 (P < 0.001). CONCLUSIONS: Using a time interval of 60-90 minutes after topical application of 1% 5-ALA, the authors observed specific porphyrin fluorescence of CIN. Fluorescence spectroscopy promises to become a valuable tool for the diagnosis of CIN.

Adult↗

PubMed2000

Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminolevulinic acid.

Photodynamic (PDT) therapy is a relatively new technique with unique properties that make it attractive for the local treatment of superficial epithelial disorders. The objective of this study was to investigate the clinical response of PDT with the photosensitizing agent 5-aminolevulinic acid (5-ALA) in patients with vulvar intraepithelial neoplasia (VIN) grades 1 to 3. Twenty-five patients with 111 lesions of VIN 1-3 were topically sensitized with 10 ml of a 20% solution of 5-ALA and treated with 57 cycles of laser light at 635 nm (100 J/cm(2)). Seventy (64%) of the 111 VIN lesions regressed after various PDT cycles. A complete response was achieved in 13 patients (52%) with 27 lesions. All patients with VIN 1 and mono- and bifocal VIN 2-3 showed complete clearance. However, a complete response could be achieved in only 4 (27%) of 15 women with multifocal VIN 2-3, whereas a partial response was noted in 9 of these patients with a total of 70 lesions, out of which 44 (63%) lesions disappeared. No response was seen in 2 patients with multifocal VIN 3. Histological assessment of the fluorescence-directed biopsies revealed that increased pigmentation and hyperkeratosis of the lesions were associated with low response rates. PDT using 5-ALA represents an alternative treatment modality for VIN which is easy to perform and has the advantage of minimal tissue destruction, low side effects and excellent cosmetic results. However, multifocal VIN disease with pigmented and hyperkeratinic lesions remains difficult to treat.

Adult↗

PubMed2000

20q13 and cyclin D1 in ovarian carcinomas. Analysis by fluorescence in situ hybridization.

In ovarian carcinomas, alterations of the chromosomal region 20q13 and the cyclin D1 gene have been described. This study has sought to determine their prognostic significance. Fluorescence in situ hybridization (FISH) on dissociated nuclei and paraffin sections with DNA probes for 20q13.2 and cyclin D1, as well as immunohistochemistry (cyclin D1), were applied to formalin-fixed tissue of 69 invasive ovarian carcinomas, mainly of serous type. On dissociated nuclei 33/47 cases (70%) and on tissue sections 13/66 cases (20%) demonstrated an increase of 20q13.2 copies. The presence of > or =4 copies per nucleus (isolated nuclei) and > or =3 copies per nucleus (sections) was associated with an adverse prognosis (Kaplan-Meier for FIGO stage III after stratification for residual tumour: p=0.0049 and p=0.03, respectively). Thirty-four out of 47 cases (72%) showed an increase of cyclin D1 copies. Kaplan-Meier analysis for FIGO stage III after stratification for residual tumour>2 cm or < or =2 cm revealed an unfavourable outcome for cases with more than two cyclin D1 copies (p=0.04). No correlation was seen between FISH and immunohistochemistry. Multivariate analysis identified residual tumour (p=0.0002), 20q13.2 gain (p=0.0004) and cyclin D1 gain (p=0.0343) as independent prognostic factors. It is concluded that gains of chromosomal region 20q13.2 and the cyclin D1 gene are frequent and biologically important events, with prognostic relevance, in advanced ovarian carcinomas.

Adult↗

PubMed2000

In vitro-generated stem cell leukaemia showing altered cell cycle progression with distinct signalling of the tyrosine-phosphorylated rasGAP-associated p62(dok) protein.

In an attempt to gain more insight into the events of leukaemic transformation, a cell line overexpressing MHC class II (DR) was generated by transfecting an early CD34-negative haematopoietic progenitor stem cell line with the appropriate constructs. The stable transfection with genes for DR antigens leads to cellular transformation. The DR(+) transformed cell clones express a tyrosine-phosphorylated DR heterodimer and show a significantly different morphology. DR(+) clones present the morphology of an immature myeloid neoplasia expressing alpha-naphthyl-acetate-esterase (ANAE), but neither myeloperoxidase nor CD34. While D064 cells predominately grow adherent as fibroblast-like cells, the DR(+) clones display a decrease in adherent growth. Although both cell lines express similar amounts of the interleukin-6 (IL-6) signal transducer gp130, the DR-transfected cells still show activation of STAT factors by IL-6, whereas D064 cells do not. Although the transformed clones present acceleration of cell-cycle transition and growth, the G(0)/G(1) progression inhibitor p27(kip-1) is up-regulated, while the expression of proteins involved in the S/G(2) phase transition, such as cyclin B and cdc2 (p34), is suppressed. Instead cyclin D3, one of the G(0)/G(1) progression factors, is up-regulated, as well as tyrosine-phosphorylated p62(dok), suggesting dysregulation of cell cycle-controlling proteins. In addition, DR(+) leukaemia-like cells also overexpress Bcl-2, while bax expression is suppressed, compared with the wild-type (wt) parental haematopoietic stem cell line.

Acute Disease↗

PubMed2000

Mantle cell lymphoma, in leukaemic phase with prominent splenomegaly. A report of eight cases with similar clinical presentation and aggressive outcome.

Mantle cell lymphoma (MCL) is a well-defined peripheral B-cell lymphoma usually diagnosed upon peripheral lymph node biopsy. We report eight cases of peripheral B-cell leukaemia that demonstrate presumptive evidence of mantle cell characteristics. The patients had a median age of 68.5 years, and five were male. All presented with an enlarged spleen without any peripheral lymphadenopathies, and they were leukaemic at presentation (median lymphocytosis, 38x10(9)/l). Morphological diagnosis of MCL was very difficult in five cases but easier in three because we were able to analyse either pre- or post-mortem lymph nodes and spleen. The immunophenotype of blood lymphocytosis using flow cytometry, the presence of a t(11;14)(q13;q32) and a cyclin D1 expression by leukaemic cells all fit with the diagnosis of MCL. All patients progressed and died with a median overall survival of 8 months. Multifocal areas of transformation in blastoid or large cell variants were observed in the three autopsied patients. In summary, one should consider the diagnosis of MCL at presentation in leukaemic phase even in the absence of peripheral adenopathies.

Aged↗

PubMed2000

Immunohistochemical analysis of drug resistance-associated proteins in ovarian carcinomas.

Loss of function of the tumor suppressor gene p53, increased expression of glutathione-S-transferase pi (GST7pi) and the major vault protein are involved in drug resistance of ovarian carcinomas. However, a study comparing these factors has not yet been performed. Therefore, paraffin-embedded material of 213 ovarian tumors with well-documented follow-up was used for immunohistochemical analysis of p53 protein, GSTpi, and major vault protein (antibodies LRP-56, LMR-5). Forty-six percent of the cases showed nuclear p53 accumulation. Strong immunoreactivity for GSTpi, LRP-56, and LMR-5 was seen in 50%, 36%, and 47%, respectively. p53 positivity was most often found in serous carcinomas (p < 0.05). Strong GSTpi expression was the only factor that correlated with clinical resistance to chemotherapy (p = 0.04). In the whole group, as well as in FIGO III cases stratified for residual disease < or = and >2 cm, p53 and GSTpi correlated with an adverse outcome (p = 0.01 for p53 and p = 0.04 for GSTpi). Strong LRP-56 or LMR-5 staining was associated with a tendency towards poorer prognosis, without reaching statistical significance. In multivariate analysis for FIGO III, only residual disease and p53 proved to be independent prognostic factors. Our observations confirm the prognostic significance of p53 accumulation in ovarian carcinomas. Only GSTpi immunoreactivity was significantly correlated with drug resistance.

Adenocarcinoma, Mucinous↗

PubMed2000

Quality control and sensitivity of polymerase chain reaction techniques for the assessment of immunoglobulin heavy chain gene rearrangements from fixed- and paraffin-embedded samples.

Frozen tissue is considered the gold standard if DNA is to be extracted for polymerase chain reaction (PCR) analysis. In molecular studies from paraffin-embedded material, only positive results are usually taken into account. Our goal was to evaluate both the sensitivity and the specificity of PCR techniques for immunoglobulin heavy chain (IgH) gene rearrangement according to various lengths and types of fixative before paraffin embedding. One set of studies compared IgH rearrangement in a case of mantle cell lymphoma tissue that had been fixed in 14 different ways before paraffin embedding and frozen tissue. Formalin fixation was found not to be deleterious for DNA, amplification being possible up to 15 days after fixation with good sensitivity. In contrast, the performance of PCR decreased for samples fixed in Bouin's liquid for longer than 6 hours or after 48 hours of incubation in a vacuum infiltration processor (in which Bouin's liquid-fixed and formalin-fixed samples are mixed). In addition, we undertook a retrospective study of 20 routinely processed B-cell lymphomas, with frozen formalin-fixed and Bouin's liquid-fixed tissues for each case. Of the 14 positive cases on frozen material, 13 were also clonal from paraffin-embedded tissues. Whatever the IgH locus analyzed, each time the adapted control was positive, results from paraffin-embedded material were identical to results obtained from frozen tissue. In this study, we showed that the use of paraffin-embedded tissue is efficient for the study of IgH gene rearrangement. Whenever adapted controls are used, it is even possible to assess negative results.

DNA Primers↗