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Sylke Gellrich

Publications and source records attributed to Sylke Gellrich.

12 recordsLinked to original sources
PubMed2006

CD56-positive haematological neoplasms of the skin: a multicentre study of the Cutaneous Lymphoma Project Group of the European Organisation for Research and Treatment of Cancer.

BACKGROUND: Cutaneous lymphomas expressing CD56, a neural cell adhesion molecule, are characterised in most cases by a highly aggressive clinical course and a poor prognosis. However, prognostic subsets within the CD56+ group have been difficult to identify due to the lack of uniform clinicopathological and immunophenotypical criteria. METHODS: A multicentre study was conducted by the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer to define prognostic parameters and establish diagnostic and therapeutic guidelines for CD56+ haematological neoplasms presenting primarily in the skin. RESULTS: Four different subtypes of lymphoproliferations with CD56 expression were identified: (1) haematodermic neoplasm; (2) skin infiltration as the first manifestation of CD56+ acute myeloid leukaemia; (3) nasal-type extranodal natural killer/T-cell lymphoma; and (4) "classical" cases of cutaneous T-cell lymphoma (CTCL) with co-expression of the CD56 molecule. Patients in the first three groups had a poor outcome (93% died) with a median survival rate of 11 months (95% CI 2-72 months), whereas all patients with CD56+ CTCL were alive at the last follow-up. CONCLUSION: Results show that CD56+ cutaneous lymphoproliferative disorders, with the exception of CD56+ CTCL have a very poor prognosis. It is therefore clinically important to separate CD56+ CTCL from the remaining CD56+ haematological disorders.

Adolescent↗
PubMed2006

Evaluation of B-cell clonality in archival skin biopsy samples of cutaneous B-cell lymphoma by immunoglobulin heavy chain gene polymerase chain reaction.

Polymerase chain reaction (PCR)-based detection of clonal T- and B-cells is widely used in the diagnosis of various lymphomas, including those of the skin. A large number of corresponding methods have been published. Recently, for the first time, standardized PCR protocols were developed in common by 14 European centers of lymphoma diagnosis and research (Biomed-2 protocols). Here, we have applied Biomed-2 immunoglobulin heavy chain (IgH)-PCR for clonality detection in primary cutaneous B-cell lymphoma (CBCL) and compared it with previously established methods. The DNA of 43 paraffin-embedded lesional skin biopsies of confirmed CBCL cases [27 follicle center cell lymphoma (FCCL), 11 marginal zone B-cell lymphoma/immunocytoma (MZL/IC) and five large CBCL of the lower leg (CBCL-LL)] were amplified by the Biomed-2 IgH-PCR protocols as well as using four other assays, priming also the three IgH framework regions (FR) 1-3. All PCR products were analysed by fluorescence fragment analysis. Twenty-nine of 43 (67%) CBCL samples (5/5, 100% of CBCL-LL; six of 11, 54.5% of IC/MZL; 18 of 27, 66.7% of FCCL) showed monoclonal B-cell presence complementary in all of the IgH-PCR. The three Biomed-2 PCR indicated together clonality in 24 of 43 samples (56%). Considering each method separately, the Biomed-2 FR3-PCR showed the highest rate of clonality detection (20 of 43, 47%). In conclusion, the Biomed-2 FR3-PCR is recommended for detecting B-cell clonality in archival skin samples of CBCL but should be completed by FR1- and/or FR2-PCR.

Biopsy↗
PubMed2004

Immunofluorescent and FISH analysis of skin biopsies.

Cutaneous biopsies are traditionally studied for the expression of cellular markers by immunoenzymatic techniques. However, immunofluorescent analysis is a valuable, and largely overlooked, ancillary technique that can resolve questions arising from conventional immunostaining, since it allows pairs of antigens to be simultaneously visualized. Furthermore, a novel technique, based on a combination of immunoperoxidase and immunofluorescent staining, allows three markers to be demonstrated together. Fluorescent microscopy also allows skin biopsies from lymphoma cases to be analyzed for chromosomal abnormalities by the fluorescent in situ hybridization (FISH) technique, which is now applicable to routine biopsy samples. In this review, we describe the technical aspects of immunofluorescent and FISH analysis of routine cutaneous biopsy samples.

Biopsy↗
PubMed2004

Genomic aberrations and survival in cutaneous T cell lymphomas.

Information on chromosomal aberrations in cutaneous T cell lymphomas (CTCL), is scarce. In this study, comparative genomic hybridization (CGH) was used to analyze chromosomal imbalances (CI) in 32 patients with CTCL. CI were detected in 21 patients (66%). Euchromatic loss (dim) was localized most frequently (>16%) at the chromosomal regions 17p (28%), 13q (25%), 10q (16%), and 6q (19%), and gain of chromatin (enh) at 7 (25%), 8q (25%), and 17q (16%). The pattern dim6q-enh7-enh8-dim13 was the most frequent combination of CI. The number of aberrations per tumor sample varied between 0 and 19 and correlated with clinical tumor stages: from none in stage Ia to 8.75+/-1.8 (mean+/-SEM) in stage IVa. CI occurred more frequently in aggressive subtypes (9.33+/-2.16) than in indolent (2.88+/-0.8) subtypes. A high number of CI (>/=5) was associated with shorter survival. Gain of chromatin in 8q and loss of 6q and 13q correlated with a significantly shorter survival, whereas the most frequently observed aberrations (loss in 17p and gain in 7) did not influence the prognosis. In summary, CGH analysis revealed a characteristic pattern of recurring chromosomal gains and losses in CTCL. The association of the imbalances with the clinical course of the disease suggests that genes encoded at these loci may influence tumor development and progression.

Aged↗
PubMed2004

Cellular coincidence of clonal T cell receptor rearrangements and complex clonal chromosomal aberrations-a hallmark of malignancy in cutaneous T cell lymphoma.

Detection of a clonal T cell receptor (TCR) gene rearrangement is used in the diagnosis of primary cutaneous T cell lymphomas (CTCL) whereas chromosomal aberrations serve as a diagnostic tool for leukaemias and nodal lymphomas. To what extent both approaches specify the same cell population remains unknown. We investigated the coincidence of TCR clonality with complex clonal chromosomal aberrations, indicating qualitative alteration of the affected cells, in 17 CTCL patients. Out of 41 skin, blood, and lymph node samples studied, 34 gave results in chromosome and TCR analyses. With 88%, most specimens revealed corresponding results by both techniques (27 of 34 clonal, three of 34 non-clonal). In two patients, analysis of micro-dissected cells demonstrated that neoplastic T cells bear both a dominant TCR rearrangement and a complex chromosomal aberration. The cutaneous clone was found in blood samples of 11 of 12 patients (including early stages), and investigation of follow-up skin and blood samples indicated persistence of the T cell clone in 11 of 14 cases. In conclusion, we show that dominant TCR clones and chromosomal clones converge in all stages of CTCL. These clones disseminate into blood and skin at early disease stages and persist despite therapy. The coexistence of a dominant TCR clone and a clonal chromosomal aberration can thus be used as a hallmark of malignancy.

Adult↗
PubMed2003

Anti-tumor immune responses and tumor regression induced with mimotopes of a tumor-associated T cell epitope.

Mimotopes provide an alternative to natural T cell epitopes for cancer immune therapy, as they can recruit and stimulate T cell repertoires that deviate from the repertoires engaged with the tumor and exposed to disease-related immune suppression. Here, mimotopes of a shared tumor-associated T cell epitope in cutaneous lymphoma were tested for their capacities to induce clinical and immunological responses in cancer patients. The mimotope sequences had been determined by a combinatorial peptide library approach without knowledge of the corresponding natural tumor-associated antigen. Vaccination with these mimotopes together with helper T cell-inducing antigens led to complete tumor remission in the two patients tested. After each booster vaccination, enhanced frequencies of mimotope-specific CD8+ T cells were detected in the peripheral blood of the patients, and the CTL proved to be cytotoxic and tumoricidal when tested in vitro. These data provide a first indication of clinical efficacy of mimotopes in cancer patients.

Cancer Vaccines↗
PubMed2003

T cell receptor-gamma gene analysis of CD30+ large atypical individual cells in CD30+ large primary cutaneous T cell lymphomas.

The hallmark of primary cutaneous CD30+ large T cell lymphoma are large lymphoid tumor cells, at least 75% of which, by definition, must be positive for CD30. The relatively benign clinical course of this lymphoma type has been explained with CD30-induced apoptosis, on the assumption that expression of CD30 defines the tumor clone; however, this hypothesis has not been tested on the molecular level to date. In this study we analyzed CD30+ cells in four patients with primary cutaneous CD30+ large T cell lymphoma by single cell polymerase chain reaction of T cell receptor-gamma genes followed by sequencing. Here, we demonstrate that most of the large CD30+ atypical cells possessed identical T cell receptor-gamma gene rearrangements, indicative of clonal proliferation. Nevertheless, polyclonally rearranged T cells were present in all CD30+ samples studied. In addition, one patient showed a second clone in a separate biopsy and three of four patients showed chromosomal imbalances as revealed by comparative genomic hybridization. Taken together, our data suggest that the CD30+ population in primary cutaneous CD30+ large T cell lymphoma indeed contains the tumor clone, thus providing molecular support for a link between clinical course and CD30-related signaling. Importantly, however, CD30 expression does not define the tumor clone as bystander T cells, as well as occasional additional clones, are also present in this population.

Adult↗
PubMed2003

Peripheral blood T-cell clonality in mycosis fungoides and nonlymphoma controls.

In mycosis fungoides (MF), T-cell clonality is reported in about 90% of skin and 40% of blood samples. However, identity of blood and cutaneous T-cell clone and prognostic relevance of blood T-cell clonality remain controversial. By PCR/fluorescence fragment analysis with estimation of clonal fragment lengths and relative peak heights, we objectively identified T-cell clonality unrelated to malignant lymphoproliferation in healthy donors (5/38), autoimmune dermatoses (3/8), and nonlymphoma skin cancer (9/39). This T-cell expansion of undetermined significance (TEXUS) was also found in 8/64 MF patients. Dissemination of neoplastic cells into blood, as identified by identical clonal fragment lengths in blood and skin, was detected in 23/64 MF patients. When monitoring for progression at TNM stage for a mean of 45.7 months, univariate analysis identified age of >60 years and detection of a related blood T-cell clone to be of prognostic relevance, whereas detection of TEXUS, sex, TNM stage at initial diagnosis, and detection of a cutaneous T-cell clone were irrelevant. Although multivariate analysis was not possible, further stratification clearly indicated an age of >60 years to be the predominating prognostic factor. In conclusion, investigation of T-cell clonality in skin and blood samples at the initial diagnosis cannot predict the clinical course of MF and the occurrence of TEXUS should be considered when assessing blood T-cell clonality.

Adult↗