Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Molecular Classification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed2026

The Impact of Molecular Characteristics on the Efficacy of Frontline Immune Checkpoint Inhibitor Therapy in Patients with Metastatic Melanoma.

Background: Metastatic melanoma in East Asian populations is enriched for acral and mucosal subtypes and harbors a distinct molecular landscape compared with Western cutaneous melanoma. However, data on the efficacy of first-line immune checkpoint inhibitor (ICI) therapy and on the impact of molecular characteristics on treatment effect in this population remain limited. We aimed to characterize the genomic landscape of an East Asian metastatic melanoma cohort and to evaluate the predictive values of molecular markers for first-line ICI therapy. Methods: This study included 135 patients with metastatic melanoma who received first-line ICI at Samsung Medical Center between January 2022 and December 2025. Of these, 108 with paired next-generation sequencing (NGS) data were included in the molecular analysis. Survival outcomes were estimated by the Kaplan-Meier method, and the prognostic value of molecular subtype was assessed using univariable and multivariable Cox proportional hazards models. Results: Mucosal melanoma was the most common primary site (58, 43.0%), followed by acral melanoma (31, 23.0%) and cutaneous melanoma (25, 18.5%); 4 (3.0%) had uveal melanoma and 17 (12.6%) had melanoma of other or unknown primary origin. The overall objective response rate to first-line ICI was 37.8% (51 of 135), and median progression-free survival (PFS) was 6.2 months (95% confidence interval [CI] 4.0-9.6). Using the hierarchical classification, 108 patients were classified into five molecular subtypes: BRAF-altered (n = 17, 15.7%), RAS-altered (n = 17, 15.7%), KIT-altered (n = 15, 13.9%), and NF1-altered (n = 7, 6.5%), and quadruple-wild-type (n = 52, 48.1%). TMB-high status (10.2%) showed no significant association with outcomes. Molecular subtype was significantly associated with PFS (log-rank p = 0.009). After multivariable adjustment, BRAF fusion (hazard ratio [HR] 5.05, 95% CI 1.70-14.98, p = 0.003) and KIT-altered status (HR 2.91, 95% CI 1.46-5.77, p = 0.002) emerged as independent adverse prognostic factors, whereas BRAF V600 single-nucleotide variants did not differ significantly from quadruple-wild-type. Conclusions: In this East Asian metastatic melanoma cohort, BRAF fusion and KIT alterations were independent adverse prognostic factors for first-line ICI. These findings suggest that BRAF fusion and KIT-altered tumors may represent distinct subgroups that warrant further investigation.

immune checkpoint inhibitor↗
PubMed2003

Primary cutaneous lymphomas: a review with current treatment options.

Primary cutaneous T- and B-cell lymphomas are a heterogenous group of diseases with varied clinical presentations and prognosis. The use of new molecular, histological, and clinical criteria have enhanced the recognition of primary cutaneous T- and B-cell lymphomas. Compared to their nodal counterpart they have a different clinical behavior and therefore require a different treatment approach. Independent predictive factors identified clinically, histologically, and by immunopheno- and immunogenotyping are essential to assess the appropriate treatment for each subtype. The European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Study Group provide a classification of cutaneous lymphomas taking into account of the histological and molecular features. Based on this classification we will provide a summary of the current medical literature in diagnosis, treatment, and prognosis for primary cutaneous lymphomas with emphasis on new treatment strategies.

Antibodies, Monoclonal↗
PubMed2002

[The new WHO classification of tumors of the nervous system 2000. Pathology and genetics].

New developments in neuro-oncology have prompted an update of the World Health Organization (WHO) classification of tumors of the nervous system. Major changes include the addition of new entities and the refinement of criteria for the diagnosis and grading of various neoplasms, in particular the meningiomas. As novel clinico-pathological entities, the chordoid glioma of the third ventricle, the atypical teratoid/rhabdoid tumor (AT/RT), the solitary fibrous tumor, and the perineurioma have been listed. The former lipomatous medulloblastoma of the cerebellum, previously incorporated in the family of embryonal tumors, is now classified as cerebellar liponeurocytoma. The term mixed pineocytoma/pineoblastoma has been replaced by pineal parenchymal tumor of intermediate differentiation. Furthermore, the large cell medulloblastoma and the tanycytic ependymoma were established as novel tumor variants. A separate chapter on the peripheral neuroblastic tumors has now been included in the classification. Substantial revisions were introduced in the meningioma chapter. For both atypical meningioma WHO grade II and anaplastic meningioma WHO grade III, histopathological criteria are now precisely defined. An important new addition to the WHO 2000 classification of nervous system tumors is the inclusion of molecular pathology findings. With this combination of pathology and genetics it has set the stage for a new format of the WHO tumor classification series.

Astrocytoma↗
PubMed2005

Molecular pathogenesis of Hodgkin's lymphoma.

According to the WHO classification, Hodgkin's lymphoma (HL) is subdivided into a classical variant and a nodular lymphocyte predominant variant which are characterized by the presence of Hodgkin's and Reed-Sternberg (H-RS) cells or lymphocytic and histiocytic (L&H) cells, respectively. This article reviews genetic characteristics and transcriptional changes of H-RS and L&H cells, including recent knowledge about transforming mechanisms and signaling pathways that contribute to the antiapoptotic phenotype displayed by H-RS and L&H cells. We also discuss major cellular and molecular mediators contributing to the establishment and maintenance of a reactive background in HL-affected tissues. We believe that an in-depth understanding of the pathogenesis of HL will eventually lead to the development of novel biologically based therapeutic strategies in the near future.

Female↗
PubMed2002

Testing the new animal phylogeny: first use of combined large-subunit and small-subunit rRNA gene sequences to classify the protostomes.

Although the small-subunit ribosomal RNA (SSU rRNA) gene is widely used in the molecular systematics, few large-subunit (LSU) rRNA gene sequences are known from protostome animals, and the value of the LSU gene for invertebrate systematics has not been explored. The goal of this study is to test whether combined LSU and SSU rRNA gene sequences support the division of protostomes into Ecdysozoa (molting forms) and Lophotrochozoa, as was proposed by Aguinaldo et al. (1997) (Nature 387:489) based on SSU rRNA sequences alone. Nearly complete LSU gene sequences were obtained, and combined LSU + SSU sequences were assembled, for 15 distantly related protostome taxa plus five deuterostome outgroups. When the aligned LSU + SSU sequences were analyzed by tree-building methods (minimum evolution analysis of LogDet-transformed distances, maximum likelihood, and maximum parsimony) and by spectral analysis of LogDet distances, both Ecdysozoa and Lophotrochozoa were indeed strongly supported (e.g., bootstrap values >90%), with higher support than from the SSU sequences alone. Furthermore, with the LogDet-based methods, the LSU + SSU sequences resolved some accepted subgroups within Ecdysozoa and Lophotrochozoa (e.g., the polychaete sequence grouped with the echiuran, and the annelid sequences grouped with the mollusc and lophophorates)-subgroups that SSU-based studies do not reveal. Also, the mollusc sequence grouped with the sequences from lophophorates (brachiopod and phoronid). Like SSU sequences, our LSU + SSU sequences contradict older hypotheses that grouped annelids with arthropods as Articulata, that said flatworms and nematodes were basal bilateralians, and considered lophophorates, nemerteans, and chaetognaths to be deuterostomes. The position of chaetognaths within protostomes remains uncertain: our chaetognath sequence associated with that of an onychophoran, but this was unstable and probably artifactual. Finally, the benefits of combining LSU with SSU sequences for phylogenetic analyses are discussed: LSU adds signal, it can be used at lower taxonomic levels, and its core region is easy to align across distant taxa-but its base frequencies tend to be nonstationary across such taxa. We conclude that molecular systematists should use combined LSU + SSU rRNA genes rather than SSU alone.

Animals↗
PubMed2001

Characterization and partial sequencing of species-specific sarcoplasmic polypeptides from commercial hake species by mass spectrometry following two-dimensional electrophoresis.

The Merluccidae family comprises marine species, some of them of high commercial value and others less appreciated, whose commercialization in Europe under the generic name of "hake" is highly remarkable. The potential of proteomics was employed in this study with the aim of achieving the differential characterization of five different hake species: Merluccius merluccius (European hake), M. australis (Southern hake), M. hubbsi (Argentinian hake), M. gayi (Chilean hake), and M. capensis (Cape hake), some of them very closely related. Species-specific polypeptides were observed for the five hake species studied in isoelectric focusing (IEF) and/or two-dimensional electrophoresis (2-DE) high-resolution gels. The peptide mass maps of two polypeptide groups, previously selected by 2-DE analysis as potentially species-specific, were obtained by "in-gel" tryptic digestion, followed by matrix assisted laser desorption/ ionization-time of flight-mass spectrometry (MALDI-TOF-MS). Analysis of group A polypeptides (with pI in the range of 5.0-5.5 and molecular mass of 17 kDa), allowed the differential classification of the hake species into two groups: the East Atlantic coast group and the West Atlantic coast group. Moreover, the peptide mass-maps from the heat-resistant parvalbumin fraction (pI below 4.5; molecular mass <12 kDa) allowed the detection of a peptide characteristic of M. australis not present in the other four hake species tested. A specific 17 kDa protein from M. merluccius was also partially sequenced by nanospray-ion trap-tandem MS, revealing a high homology with rat nucleoside diphosphate kinase A (NDKA). This work opens the way to the application of proteomics to the differential characterization of commercial hake species at the molecular level.

Amino Acid Sequence↗
PubMed1990

Drugs and receptors. An overview of the current state of knowledge.

This paper reviews the theoretical concepts and methods utilised with isolated tissues to characterise drugs and drug receptors. Specifically the impact, on the in vitro measurement of agonist affinity and relative efficacy, of the idea that receptors bind to transduction proteins in the lipid bilayer of the cell membrane is discussed. The effects of ternary complex formation of agonist-receptor equilibria raise theoretical objections to the measurement of agonist receptor equilibrium dissociation constants. Possible 'promiscuity' of receptors with respect to the G-proteins with which they can interact makes classification of receptors by agonists suspect. The use of Schild analysis for the measurement of antagonist affinity and subsequent classification of receptors is considered in the light of recent data showing that estimates calculated with this method are heterogeneous. Resultant analysis for the detection of allosteric effects is also discussed. Lastly, the impact of molecular biology on the drug and drug receptor classification process is considered, as well as the effects of pathological processes on drug action at the receptor level.

Animals↗
PubMed1993

Use of a rule based graph-theoretical system in evaluating the activity of a class of nucleoside analogues against human immunodeficiency virus.

A rule based graph-theoretical system has been used to evaluate qualitatively the activity of a class of nucleoside analogues against human immunodeficiency virus (HIV). The system identifies biologically relevant vertices (atoms) in the molecular graphs of the compounds which have the biological activity of interest. The idea is to relate biological activity with the structural or substructural characteristics of the compounds from the point of view of molecular topology (connectivity). The system brings vertices of similar or close topological environment in the respective compounds together and this is reflected in the ranges of values formed by a distance based index of the vertices, the 'distance exponent index (Dx)', where x is any real number. It is found that the system makes correct prediction of the activity of all the compounds (active as well as inactives) of both training set and the test set against HIV. It is also apparent from this study that the index D-4, which has been used here, can make a useful classification of the vertices according to their molecular environment and the system can produce significant result in a small as well as diverse data base.

Antiviral Agents↗
PubMedDate not supplied

Classification of biologically active compounds by median partitioning.

The median partitioning (MP) method was originally developed for the selection of diverse subsets from compound databases. Following this approach, property descriptors are used in subsequent steps to divide compounds into defined partitions from which representative molecules are selected. For descriptor analysis, MP was coupled to a genetic algorithm. MP subset selection does not depend on pairwise comparison of molecules and is therefore applicable to very large compound pools. Here the MP approach was evaluated for the classification of molecules according to biological activity. A total of 317 molecules belonging to 21 different activity classes were studied. MP compound classification calculations were carried out both in the presence and absence of 2000 randomly selected "background" molecules. The performance of MP was compared to cell-based partitioning and found to be at least comparable, with up to approximately 82% of active molecules occurring in "pure" partitions consisting only of molecules sharing the same activity. Different from cell-based methods, MP classification is based on "direct" and "sequential" contributions of molecular property descriptors. Our results suggest that MP in not only an effective method for the selection of diverse subsets but also for the classification of active compounds and searching for molecules with desired activity.

Computer Simulation↗
PubMed2026

Breed classification of Lao People's Democratic Republic (Lao PDR) and Thai native chickens using synchrotron radiation-based Fourier transform infrared spectroscopy and genotyping by sequencing.

Lao PDR harbors substantial genetic diversity in native chicken populations, representing an important resource for sustainable production and long-term food security. This study aimed to classify five Lao native chicken breeds-Ou, Black Bone, Horn Chou, Yolk, and Chae-and to discriminate them from a Thai native breed, Leung Hang Khao (LK), using integrative genotype-based approaches. Blood samples were collected from 50 LK and Lao native chickens (32 Ou, 10 Black Bone, 9 Horn Chou, 121 Yolk, and 41 Chae). Genomic DNA was extracted and analyzed using synchrotron radiation-based Fourier-transform infrared (SR-FTIR) spectroscopy to characterize biochemical composition, while genotyping-by-sequencing (GBS) was employed to identify genome-wide single nucleotide polymorphisms (SNPs). SR-FTIR analysis revealed highly significant differences among breeds in nucleotide-associated functional groups, including thymine, adenine, guanine, cytosine, as well as DNA backbone and deoxyribose components (P < 0.001). Multivariate analyses demonstrated that principal component analysis (PCA) of SR-FTIR spectra effectively discriminated chicken breeds, while hierarchical cluster analysis (HCA) further resolved them into two major clusters with distinct sub-clusters, reflecting variation in DNA biochemical composition. In contrast, GBS analysis identified 1484 common SNPs; however, PCA based on SNP data showed limited resolution in clearly separating breeds, despite revealing similar clustering trends. Overall, the results highlight the strong discriminatory power of SR-FTIR spectroscopy for rapid and effective classification of native chicken breeds at the molecular level, outperforming SNP-based differentiation under the current marker density. This study provides novel insights into the application of synchrotron-based spectroscopic techniques in poultry genetics and contributes valuable baseline information for the conservation and utilization of Lao native chicken genetic resources.

Breed classification↗
PubMed1996

Pediatric epilepsy syndromes: an update and critical review.

Epilepsy syndromes occupy an important position in the current nosology of the epilepsies, describing and classifying seizure disorders with shared clinical and EEG features. Increasingly, this schema is being refined as new information becomes available and our understanding of etiology and presentation of each syndrome widens. Advances in neuroimaging and neurogenetics have been particularly important and are likely to fundamentally change our concepts of syndrome classification. At present, the International League Against Epilepsy classification of epilepsy syndromes according to presumed localization (partial, generalized, undetermined) and etiology (idiopathic, cryptogenic, symptomatic). In clinical practice, it is often useful to conceptualize epilepsy syndromes according to their usual age at presentation, which greatly facilitates syndrome identification in new patients and recognizes the age-related expression of many childhood epilepsies. Definitional problems exist for many pediatric epilepsy syndromes, particularly the epileptic encephalopathies of early infancy, the benign epilepsies of infancy and childhood, the myoclonic epilepsies of infancy and early childhood, and the idiopathic generalized epilepsies of childhood and adolescence. It is likely that further input from the fields of molecular genetics and neuroimaging will enable the classification of epilepsies to become more etiologically oriented and disease specific.

Adolescent↗
PubMed2003

Fish microsporidia: fine structural diversity and phylogeny.

Structural diversity of fish microsporidian life cycle stages and of the host-parasite interface is reviewed. In the infected cell of the fish host, microsporidia may either cause serious degradation of the cytoplasm and demise of the cell, or they may elicit host cell hypertrophy, producing a parasite-hypertrophic host cell complex, the xenoma. The structure of the xenoma and of its cell wall may differ according to the genus of the parasite, and seems to express properties of the parasite rather than those of the host. In merogony, the parasite cell surface interacts with the host cell in diverse ways, the most conspicuous being the production of thick envelopes of different types. Sporogony stages reveal different types of walls or membranes encasing the sporoblasts and later the spores and these envelopes may be of host or parasite origin. Nucleospora differs from all other fish microsporidia by its unique process of sporogony. Except for the formation of conspicuous xenomas, there are no essentially different structures in fish-infecting microsporidia compared with microsporidia from other hosts. Although the structures associated with the development of fish microsporidia cannot be attributed importance in tracing the phylogeny, they are relevant for practical determination and assessing the relation to the host. The possibility of the existence of an intermediate host is discussed. Higher-level classification of Microsporidia is briefly discussed and structure and evolutionary rates in microsporidian rDNA are reviewed. Discussion of rDNA molecular phylogeny of fish-infecting microsporidia is followed by classification of these parasites. Most form a rather cohesive clade. Outside this clade is the genus Nucleospora, separated at least at the level of Order. Within the main clade, however, there are six species infecting hosts other than fish. Based on data available for analysis, a tentative classification of fish-infecting microsporidia into five groups is proposed. Morphologically defined groups represent families, others are referred to as clades. Group 1, represented by family Pleistophoridae, includes Pleistophora, Ovipleistophora and Heterosporis; Vavraia and Trachipleistophora infect non-fish hosts. Group 2, represented by family Glugeidae, is restricted to genus Glugea and Tuzetia weidneri from crustaceans. Group 3 comprises three clades: Loma and a hyperparasitic microsporidian from a myxosporean; Ichthyosporidium and Pseudoloma clade and the Loma acerinae clade. For the latter species a new genus has to be established. Group 4 contains two families, Spragueidae with the genus Spraguea and Tetramicridae with genera Microgemma and Tetramicra, and the Kabatana and Microsporidium seriolae clade. Group 5 is represented by the family Enterocytozoonidae with the genus Nucleospora and mammal-infecting genus Enterocytozoon.

Animals↗
PubMed1999

Mitochondrial DNA analysis of sympatric morphotypes of bottlenose dolphins (genus: Tursiops) in Chinese waters.

The classification within the bottlenose dolphin (genus Tursiops) is controversial. Although many morphological variants exist, most authors have concluded that the genus is composed of a single species, Tursiops truncatus (Montagu 1821). Two distinct morphotypes of bottlenose dolphins, which have been referred to as T. truncatus and T. aduncus, exist in sympatry in Chinese waters. Comparisons of a 386-bp fragment of the mitochondrial DNA (mtDNA) control region (n = 47) indicated that the two sympatric morphotypes were genetically distinct, with seven fixed site differences and a sequence divergence of approximately 4.4%. Phylogenetic analyses using maximum likelihood, neighbour-joining and maximum parsimony approaches showed that the truncatus-type dolphins from Chinese waters were more closely related to Atlantic Ocean truncatus-type than to the sympatric aduncus-type dolphins. The Atlantic truncatus-type dolphins also shared the same diagnostic sites that separated Chinese truncatus-type from aduncus-type dolphins. The molecular data agreed completely with the morphological classifications of the specimens. This congruence is strong evidence that the sympatric morphotypes in Chinese waters are reproductively isolated and comprise two distinct species. These findings have important implications for the conservation of bottlenose dolphins in Chinese waters.

Animals↗
PubMed1997

Review: hepatitis delta.

The causative agent of hepatitis delta virus (HDV) is the most unusual of all causative agents for all hepatitis viruses. Current knowledge of the molecular biology of HDV strengthens its proposed classification within the satellites, a family of subviral agents, some of which are pathogens of higher plants. Hepatitis delta virus is the only virus in the satellite family known to infect animal species, with hepatitis D having affected more than 10 million people worldwide who are also infected with its helper virus, HBV. Recently, the world map for hepatitis D appears somewhat modified, with decreasing HDV prevalence in certain areas and some new foci of HDV endemicity. Despite changing HDV prevalence, hepatitis. D, particularly the chronic form, is still an important health problem worldwide in terms of morbidity and mortality (mainly due to chronic liver disease, including hepatocellular carcinoma). Molecular studies have greatly advanced our understanding of the life cycle of HDV and of the function of its proteins. The new molecular information is of clinical relevance, with implications for the pathogenesis of liver damage, the diagnosis of HDV infection, for the natural course of the disease and, potentially, for therapy. Sensitive assays for HDV-RNA by polymerase chain reaction and sequencing techniques have clarified the patterns of HDV transmission and have confirmed the existence of unusual clinical forms of the virus and their relationship to replicative levels and genotypes of HDV. Prevention and treatment of hepatitis D are still in their infancy. However, liver transplantation for delta cirrhosis has proven far more successful than in any other viral form of cirrhosis, with few reinfections of the grafted liver, and has given important information on HDV biology and the pathogenesis of liver damage.

Animals↗
PubMed1999

Molecular phylogenetic studies on Theileria parasites based on small subunit ribosomal RNA gene sequences.

Classification of Theileria parasites of south-east Asian countries is still ambiguous due to the lack of basic studies, especially their molecular genetic information. In this study, we included 6 known species and 14 unclassified Theileria parasite isolates: Theileria annulata, Theileria parva, Theileria taurotragi, Theileria sergenti, Theileria buffeli, Theileria types Sable, Theileria types A, B, B1, B2, C, D, E, F, G, G1, Theileria type Medan (Indonesia), Theileria type Ipoh (Malaysia) and Theileria type Thong Song (Thailand). Small subunit ribosomal RNA (srRNA) nucleotide sequence data were collected by PCR, cloning and dideoxy sequencing. The srRNA nucleotide sequences were aligned and analyzed by distance methods, maximum parsimony algorithms and maximum likelihood methods to construct phylogenetic trees. Bootstrap analysis was used to test the strength of the different phylogenetic reconstructions. The data indicated that all of the tree-building methods gave very similar results. This study identified two groups of Theileria, the pathogenic and benign groups, which are strongly supported by bootstrap analysis. The analysis also indicated that three subgroups (A, B and C) were generated within the benign Theileria group whereas the classification of Theileria type D and Thong Song is questionable. However, more basic information such as life cycle differences, vectors, modes of transmission, virulent and genetic/sexual compatability is essential for clearer taxonomic definition of the benign Theileria parasites.

Animals↗
PubMed2001

Stage progression in Ta papillary urothelial tumors: relationship to grade, immunohistochemical expression of tumor markers, mitotic frequency and DNA ploidy.

PURPOSE: We studied 363 patients with stage Ta bladder tumors during long-term followup who were classified according to the 1998 WHO and International Society of Urological Pathology consensus classifications. We determine whether various immunohistochemical and molecular markers could predict tumor progression. MATERIALS AND METHODS: A total of 680 patients in western Sweden with a first diagnosis of bladder carcinoma in 1987 and 1988 were registered and followed for at least 5 years. There were 363 (53%) tumors that were papillary stage pTa. The tumors were classified as papillary urothelial neoplasm of low malignant potential in 95 patients, low grade papillary urothelial carcinoma in 160 and high grade carcinoma in 108. Of the patients in the latter group 95 were subdivided into WHO grade 2 and 13 into WHO grade 3. Tissue from the primary tumors that progressed in stage during followup was further analyzed with immunohistochemical methods (p21, p53, Ki67 and pRb), DNA ploidy and mitotic frequency. The results were compared with those in matched controls (nonprogressors). RESULTS: Recurrence developed in 35% of patients with papillary urothelial neoplasm of low malignant potential compared to 71% with low grade urothelial carcinoma and 73% with high grade carcinoma (p <0.0001). No papillary urothelial neoplasm of low malignant potential progressed in stage. Disease progressed in 4% of patients with low grade compared to 23% with high grade carcinoma (p <0.0001). Of the patients with WHO grade 3 disease progressed in 45% compared to grade 2 in 20% (p <0.0011). At first diagnosis p53 score was significantly higher (p <0.0022) among patients with WHO grade 2 carcinoma which later progressed compared to that in matched controls but there was no significant difference regarding the other markers. In contrast to grade 2 most grade 3 carcinoma was aneuploid, had high mitosis frequency, high p53 and Ki67 scores as well as loss of retinoblastoma gene expression. CONCLUSIONS: The 1988 WHO and International Society of Urological Pathology consensus classifications divide noninvasive papillary bladder tumors into 3 subgroups with different clinical behavior, which seems to be an advantage compared with the 1973 WHO classification. A disadvantage is that the high grade carcinoma group contains 2 subgroups with different progression rates and immunohistochemical marker profiles, corresponding to the 1999 WHO grades 2 and 3. Grade 2 tumors in patients that progressed in stage years later seem to have different immunohistochemical and molecular marker profiles compared to those in matched controls.

Aged↗
PubMed2003

Molecular immunoglobulin/T- cell receptor clonality analysis in cutaneous lymphoproliferations. Experience with the BIOMED-2 standardized polymerase chain reaction protocol.

BACKGROUND AND OBJECTIVES: Molecular clonality analysis of immunoglobulin (Ig) and T-cell receptor (TCR) genes is a widely used diagnostic tool for discrimination between polyclonal, oligoclonal, and monoclonal lymphoproliferative skin lesions. We studied Ig/TCR clonality in a series of 60 patients with an initial suspicion of (primary) cutaneous B- or T-cell lymphoma (CBCL/CTCL). Clonality of Ig/TCR gene rearrangements was assessed by Southern blot (SB) and polymerase chain reaction (PCR) analysis using standardized PCR primers and protocols of the BIOMED-2 Concerted Action BMH4-CT98-3936. The obtained PCR products were subjected to heteroduplex (HD) and GeneScan (GS) analysis. We compared the data of 154 samples with the histopathologic diagnosis, based on the EORTC classification of skin lymphomas. DESIGN AND METHODS: Molecular results were largely concordant with histopathology. In 12 CBCL patients PCR analysis of Ig gene rearrangements detected clonality in 83% of cases whereas SB did so in 92%. Clonal TCR gene rearrangements were detected by SB in 68% of CTCL patients, whereas TCRG and TCRB PCR analysis detected clonality in 76% and 66% of cases, respectively. PCR GS analysis of TCR rearrangements appeared to be slightly more informative than HD analysis. Clonality assessment was particularly informative for studying involvement of extracutaneous sites, such as regional lymph nodes, peripheral blood, and bone marrow. INTERPRETATION AND CONCLUSIONS: Our study shows that the BIOMED-2 multiplex PCR analysis strategy is a reliable and useful technique in the diagnostic process of patients with an initial suspicion of (primary) CBCL/CTCL and for assessment of extracutaneous dissemination, provided that the results are interpreted in the context of clinical, histologic and immunophenotypic data.

Clone Cells↗
PubMed2000

Impact of molecular analysis in the diagnosis of cutaneous lymphoid infiltrates.

The diagnosis and classification of cutaneous lymphomas is a challenge for the dermatopathologist. This is particularly true for determining the distinction between a malignant lymphoma and a benign reactive infiltrate (pseudolymphoma). Recent advances in molecular genetics, as the determination of clonality of lymphoid infiltrates, have emerged as an important tool to overcome these diagnostic dilemmas. In our experience, more than 90% of cutaneous T-cell lymphomas have a rearrangement of the T-cell receptor gamma chain gene, whereas clonal rearrangements in cutaneous T-cell pseudolymphomas could not be found. However, the demonstration of clonality does not necessarily indicate malignancy. There have been several reports that have identified clonal lymphoid proliferations in pityriasis lichenoides et varioliformis acuta, pseudolymphomas, and lichen planus. For this reason one must carefully evaluate the information that is provided by these techniques. The results should always correlate with clinical, histologic, and immunophenotypic data to achieve the correct diagnosis.

Blotting, Southern↗