PubMed Health⌕ Search

Biomedical subjects

T Aigner

Publications and source records attributed to T Aigner.

At least 19 recordsLinked to original sources
PubMed2003

[Allergy-associated colitis. Characterization of an entity and its differential diagnoses].

There is substantial evidence that allergic reactions exist in the gastrointestinal tract (GI). However, patients with food allergy-related enteropathy pose a diagnostic challenge to physicians because the clinical features are variable, unspecific, occur in other gastrointestinal disorders, and specific diagnostic tools are missing. Several recent studies and reviews have focused on the function of eosinophilic granulocytes in GI disease. The role of eosinophils in the pathophysiology of GI hypersensitivity reactions is poorly defined. However, some findings have been reported that imply an involvement of eosinophils in allergic reactions of the gut. The presumptive histology of allergy-associated colitis in colonic and ileal biopsies is based on prominent pure eosinophilic infiltration of a normal lamina propria, submucosa and epithelium with variable degrees of degranulation. An immunoperoxidase stain for eosinophilic peroxidase is supportive in establishing the diagnosis if suspected. Neutrophils or mononuclear infiltrates are not significantly increased and damage to the intestinal tissue is not prominent. Despite characteristic histologic changes in colonic biopsy specimens, a final diagnosis depends on careful clinical examination and exclusion of several differential diagnoses.

Colitis↗
PubMed2003

Osteophyte development--molecular characterization of differentiation stages.

OBJECTIVE: Osteophytes are non-neoplastic osteo-cartilaginous protrusions growing at the margins of osteoarthritic joints. They can not only be considered as in situ repair tissue, but also represent an excellent in vivo model for induced cartilage repair processes. Our focus was to identify different steps of osteophyte development via analysis of expression patterns of marker genes of chondrocytic differentiation. DESIGN: We performed an extensive analysis of the presence and expression of matrix components using histochemical, immunohistochemical and in situ hybridization technology. RESULTS: Four different stages of osteophyte formation could be identified based on histomorphological and cell biological parameters: starting from mesenchymal condensates, chondrogenic differentiation is indicated by the onset of Col2A and aggrecan expression (stage I). Stage II shows fibrocartilage with an admixture of cartilaginous and fibrous matrix components such as Col2 and aggrecan on the one hand and Col1 on the other hand. The proliferating osteophyte (stage III) shows a zonal organization similar to the fetal growth plate cartilage with extensive chondrocyte hypertrophy in the zones next to ongoing endochondral bone formation. 'Mature' osteophytes (stage IV) resembled largely articular hyaline cartilage with a predominance of Col2 and aggrecan and Col6 found mainly pericellularily. CONCLUSIONS: The development of osteophytes is a good in vivo model to pursue chondrocyte differentiation from pluripotent mesenchymal cells to mature or hypertrophic chondrocytes in situ in the adult. The analysis of marker molecules of mesenchymal differentiation allows to identify different stages of repair tissue development and the transformation from fibrous tissue to neo-cartilage. Tissue architecture and matrix composition in mature osteophytes suggests that metaplastic neo-cartilagenous tissue might be one potential source of cartilage repair tissue in the adult joint.

Aged↗
PubMed2003

YKL-39 (chitinase 3-like protein 2), but not YKL-40 (chitinase 3-like protein 1), is up regulated in osteoarthritic chondrocytes.

OBJECTIVE: To investigate quantitatively the mRNA expression levels of YKL-40, an established marker of rheumatoid and osteoarthritic cartilage degeneration in synovial fluid and serum, and a closely related molecule YKL-39, in articular chondrocytes. METHODS: cDNA array and online quantitative polymerase chain reaction (PCR) were used to measure mRNA expression levels of YKL-39 and YKL-40 in chondrocytes in normal, early degenerative, and late stage osteoarthritic cartilage samples. RESULTS: Expression analysis showed high levels of both proteins in normal articular chondrocytes, with lower levels of YKL-39 than YKL-40. Whereas YKL-40 was significantly down regulated in late stage osteoarthritic chondrocytes, YKL-39 was significantly up regulated. In vitro both YKLs were down regulated by interleukin 1beta. CONCLUSIONS: The up regulation of YKL-39 in osteoarthritic cartilage suggests that YKL-39 may be a more accurate marker of chondrocyte activation than YKL-40, although it has yet to be established as a suitable marker in synovial fluid and serum. The decreased expression of YKL-40 by osteoarthritic chondrocytes is surprising as increased levels have been reported in rheumatoid and osteoarthritic synovial fluid, where it may derive from activated synovial cells or osteophytic tissue or by increased matrix destruction in the osteoarthritic joint. YKL-39 and YKL-40 are potentially interesting marker molecules for arthritic joint disease because they are abundantly expressed by both normal and osteoarthritic chondrocytes.

Adipokines↗
PubMed2003

Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. A prospective, comparative trial.

BACKGROUND: Current methods used to restore the joint surface in patients with localized articular cartilage defects include transplantation of an autologous osteochondral cylinder and implantation of autologous chondrocytes. The purpose of this study was to evaluate the clinical and histological outcomes of these two techniques. METHODS: We performed a prospective clinical study to investigate the two-year outcomes in forty patients with an articular cartilage lesion of the femoral condyle who had been randomly treated with either transplantation of an autologous osteochondral cylinder or implantation of autologous chondrocytes. Biopsy specimens from representative patients of both groups were evaluated with histological staining, immunohistochemistry, and scanning electron microscopy. RESULTS: According to the postoperative Lysholm score, the recovery after autologous chondrocyte implantation was slower than that after osteochondral transplantation at six months (p < or = 0.015), twelve months (p < or = 0.001), and twenty-four months (p < or = 0.012). On the basis of the Meyers score and the Tegner activity score, the results were equally good with the two methods two years after treatment. Histomorphological evaluation of biopsy specimens within two years after autologous chondrocyte implantation demonstrated a complete, mechanically stable resurfacing of the defect in all patients. The tissue consisted mainly of fibrocartilage, while localized areas of hyaline-like regenerative cartilage could be detected close to the subchondral bone. Although a gap remained at the site of the transplantation in all five biopsy specimens examined as long as two years after osteochondral cylinder transplantation, histomorphological analysis and scanning electron microscopy revealed no differences between the osteochondral transplants and the surrounding original cartilage. CONCLUSIONS: Both treatments resulted in a decrease in symptoms. However, the improvement provided by the autologous chondrocyte implantation lagged behind that provided by the osteochondral cylinder transplantation. Histologically, the defects treated with autologous chondrocyte implantation were primarily filled with fibrocartilage, whereas the osteochondral cylinder transplants retained their hyaline character, although there was a persistent interface between the transplant and the surrounding original cartilage. Limitations of our study included the small number of patients, the relatively short (two-year) follow-up, and the absence of a control group.

Adolescent↗
PubMed2002

Towards a new understanding and classification of chondrogenic neoplasias of the skeleton--biochemistry and cell biology of chondrosarcoma and its variants.

Despite substantial knowledge on the clinicopathology of chondrogenic skeletal neoplasms, only limited insights into the biology of the different tumor variants are available. There are virtually no established molecular markers for identification and classification of these neoplasms. In this paper, we present a systematic review of the biochemistry and cell biology of chondrogenic neoplasms of the bone focussing on our own recent investigations. The hallmark of all differentiated chondrogenic tumors is the presence of neoplastic chondrocytic cells responsible for the formation of the characteristic cartilaginous tumor matrix. These cells can show the full differentiation potential of physiologic chondrocytes depending on the tumor entity investigated. The high phenotypic diversity of physiologic chondrocytes explains the previously poorly understood, striking heterogeneity of the neoplastic cells and their surrounding extracellular matrix not only between different but also within chondrogenic tumors. In our studies, tumor classifications, so far based only on histomorphological criteria, were either confirmed or corrected: mesenchymal chondrosarcomas represent the prototypic neoplasm of pre-chondrogenic undifferentiated cells undergoing multifocal chondrocytic differentiation. Enchondromas, osteochondromas, and conventional chondrosarcomas are neoplasms of multi-phenotypically differentiated chondrocytes. Clear cell chondrosarcomas appear to be neoplasms of hypertrophic chondrocytic cells. A peculiar biology is displayed by dedifferentiated chondrosarcomas, which at least in most cases show neither "anaplasia" nor "dedifferentiation", but most likely "transdifferentiation" of part of the neoplastic cells to a cellular phenotype of a different mesenchymal differentiation lineage. Chondroblastomas do not show any chondroblastic differentiation at all. Our studies delineate molecular markers of chondrogenic neoplasms of the skeleton, which have the potential to be the basis of a new biology-orientated classification of skeletal neoplasms. The expression analysis of extracellular matrix genes, in particular of the collagen types, might be able to play herein a leading role in classification and diagnosis, similar to the cytokeratin subtypes or the CDs (cluster of differentiation) for the classification and diagnosis of neoplasms of the epithelia and the lymphatics.

Animals↗
PubMed2002

The C5 domain of Col6A3 is cleaved off from the Col6 fibrils immediately after secretion.

In articular cartilage, type VI collagen is concentrated in the pericellular matrix compartment. During protein synthesis and processing at least the alpha3(VI) chain undergoes significant posttranslational modification and cleavage. In this study, we investigated the processing of type VI collagen in articular cartilage. Immunostaining with a specific polyclonal antiserum against the C5 domain of alpha3(VI) showed strong cellular staining seen in nearly all chondrocytes of articular cartilage. Confocal laser-scanning microscopy and immunoelectron microscopy allowed localization of this staining mainly to the cytoplasm and the immediate pericellular matrix. Double-labeling experiments showed a narrow overlap of the C5 domain and the pericellular mature type VI collagen. Our results suggest that at least in human adult articular cartilage the C5 domain of alpha3(VI) collagen is synthesized and initially incorporated into the newly formed type VI collagen fibrils, but immediately after secretion is cut off and is not present in the mature pericellular type VI matrix of articular cartilage.

Aged↗
PubMed2002

Apoptosis, necrosis, or whatever: how to find out what really happens?

There is no doubt that thorough knowledge of apoptotic cell death is of paramount importance for many areas of current research. Despite many available ways of detecting apoptotic cell death, the analysis of apoptosis reveals considerable conceptual and technological problems. In this issue of The Journal of Pathology, Grogan and colleagues offer an interesting study, in which they present a promising model system for investigating the spatio-temporal events of initiation and progression of apoptosis (and other forms of cell death). The confusing complexity of results based on parallel experiments in this paper might be partly due to technical variability or insufficiency; more likely, however, this provides evidence that most if not all approaches thought to be 'specific' for apoptotic cell death address different aspects of cell death, have different sensitivities and specificities, and are rather complementary than redundant. Grogan and colleagues provide an excellent demonstration of the uncertainties and ambiguities which result from basically all currently available technologies, yielding, even in one system, results which are partly confusing, because they are partly contradictory. This situation is typical for cell death analysis at present-not only in the cartilage field.

Apoptosis↗
PubMed2002

Molecular pathology and pathobiology of osteoarthritic cartilage.

The biochemical properties of articular cartilage rely on the biochemical composition and integrity of its extracellular matrix. This matrix consists mainly of a collagen network and the proteoglycan-rich ground substance. In osteoarthritis, ongoing cartilage matrix destruction takes place, leading to a progressive loss in joint function. Beside the degradation of molecular matrix components, destabilization of supramolecular structures such as the collagen network and changes in the expression profile of matrix molecules also take place. These processes, as well as the pattern of cellular reaction, explain the pathology of osteoarthritic cartilage degeneration. The loss of histochemical proteoglycan staining reflects the damage at the molecular level, whereas the supramolecular matrix destruction leads to fissuring and finally to the loss of the cartilage. Chondrocytes react by increasing matrix synthesis, proliferating, and changing their cellular phenotype. Gene expression mapping in situ and gene expression profiling allows characterization of the osteoarthritic cellular phenotype, a key determinant for understanding and manipulating the osteoarthritic disease process.

Animals↗
PubMed2002

[Neoplastic chondroneogenesis as a characteristic of mesenchymal chondrosarcomas].

Mesenchymal chondrosarcomas are rare skeletal malignancies, which are typically characterized by tumor compartmentation. One tumor area is formed by small, undifferentiated neoplastic cells, whereas the second compartment is composed of cartilaginous areas. In this study, the application of in situ detection techniques enabled us to characterize the different tumor compartments according to their cellular differentiation patterns. The use of characteristic marker genes identified all steps of chondrogenesis within the different tumor compartments. Undifferentiated tumor cells in the small-cell areas were negative for vimentin and the cytoprotein S-100, whereas other tumor cells expressed collagen type IIA and vimentin indicating a chondroprogenitor cellular phenotype in these small-cell areas. Fully differentiated chondrocytic cells expressing collagen type II were found in the chondroid areas. The focal expression of type X collagen indicated hypertrophic differentiation of the neoplastic chondrocytes. The results characterize mesenchymal chondrosarcomas as skeletal malignancies that arise from undifferentiated chondroprogenitor cells and have the potential to undergo all steps of chondrocytic differentiation.

Biomarkers, Tumor↗
PubMed2002

Ultrastructural localization of type VI collagen in normal adult and osteoarthritic human articular cartilage.

OBJECTIVE: Type VI collagen is a major component of the pericellular matrix compartment in articular cartilage and shows severe alterations in osteoarthritic cartilage degeneration. In this study, we analysed the exact localization of type VI collagen in its relationship to the chondrocyte and the (inter)territorial cartilage matrix. Additionally, we were interested in its ultrastructural appearance in normal and osteoarthritic cartilage. DESIGN: Distribution and molecular appearance was investigated by conventional immunostaining, by multilabeling confocal scanning microscopy, conventional transmission, and immunoelectron microscopy. RESULTS: Our analysis confirmed the pericellular concentration of type VI collagen in normal and degenerated cartilage. Type VI collagen formed an interface in between the cell surface and the type II collagen network. The type VI collagen and the type II collagen networks appeared to have a slight physical overlap in both normal and diseased cartilage. Additionally, some epitope staining was observed in the cell-associated interterritorial cartilage matrix, which did not appear to have an immediate relation to the type II collagen fibrillar network as evaluated by immunoelectron microscopy. In osteoarthritic cartilage, significant differences were found compared with normal articular cartilage: the overall dimension of the lacunar volume increased, and a significantly increased type VI collagen epitope staining was observed in the interterritorial cartilage matrix. Also, the banded isoform of type VI collagen was found around many chondrocytes. CONCLUSIONS: Our study confirms the close association of type VI collagen with both, the chondrocyte cell surface and the territorial cartilage matrix. They show severe alterations in type VI collagen distribution and appearance in osteoarthritic cartilage. Our immunohistochemical and ultrastructural data are compatible with two ways of degradation of type VI collagen in osteoarthritic cartilage: (1) the pathologically increased physiological molecular degradation leading to the complete loss of type VI collagen filaments from the pericellular chondrocyte matrix and (2) the transformation of the fine filaments to the band-like form of type VI collagen. Both might implicate a significant loss of function of the pericellular microenvironment in osteoarthritic cartilage.

Adult↗
PubMed2001

Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis.

The reaction patterns of chondrocytes in osteoarthritis can be summarized in five categories: (1) proliferation and cell death (apoptosis); changes in (2) synthetic activity and (3) degradation; (4) phenotypic modulation of the articular chondrocytes; and (5) formation of osteophytes. In osteoarthritis, the primary responses are reinitiation of synthesis of cartilage macromolecules, the initiation of synthesis of types IIA and III procollagens as markers of a more primitive phenotype, and synthesis of active proteolytic enzymes. Reversion to a fibroblast-like phenotype, known as "dedifferentiation", does not appear to be an important component. Proliferation plays a role in forming characteristic chondrocyte clusters near the surface, while apoptosis probably occurs primarily in the calcified cartilage.

Animals↗
PubMed2001

Apoptotic cell death is not a widespread phenomenon in normal aging and osteoarthritis human articular knee cartilage: a study of proliferation, programmed cell death (apoptosis), and viability of chondrocytes in normal and osteoarthritic human knee cartilage.

OBJECTIVE: Chondrocytes are crucial for adequate matrix balance and function. Cell proliferation and, recently, extensive apoptotic cell death have been reported in osteoarthritic (OA) cartilage. Apoptotic cell death would be an obvious central factor in the initiation and progression of OA, since there is no potential for replacing articular chondrocytes in the adult. Therefore, we studied the occurrence of apoptotic cell disintegration and cell proliferation in OA and normal articular cartilage obtained from the knees of adult donors of all ages. METHODS: Following immunostaining for cellular proteins as well as staining for nuclear DNA, we performed triple-channel confocal laser scanning microscopy on thick cartilage slices to evaluate lacunar emptying and cell viability. Cell proliferation and apoptotic cell death were evaluated morphologically, by immunodetection of the proliferation-associated Ki-67 antigen, and by the TUNEL reaction. RESULTS: With the exception of the calcified layer, we were not able to detect any major (apoptotic or nonapoptotic) cell disintegration in normal young or aged articular knee cartilage. Single apoptotic cells were detected in OA articular knee cartilage. A significant increase in lacunar emptying was observed in late-stage specimens with higher Mankin scores compared with age-matched normal control cartilage specimens, but not in low-grade lesions. A significant (but lesser) increase in empty lacunae was also observed with age in normal cartilage. Cell proliferation was rarely detected in OA cartilage samples and was not detected at all in normal cartilage samples. CONCLUSION: Our results confirm the findings of previous studies showing that cell proliferation occurs in OA cartilage. They also show that, contrary to previous suggestions, apoptotic cell death is not a widespread phenomenon in aging or OA cartilage.

Adult↗
PubMed2001

Fibroblast-mediated delivery of growth factor complementary DNA into mouse joints induces chondrogenesis but avoids the disadvantages of direct viral gene transfer.

OBJECTIVE: To assess the advantages and disadvantages of a direct adenoviral and a cell-mediated approach to the induction of cartilage formation in joints by transfer of growth factor genes. METHODS: Adenoviral vectors carrying insulin-like growth factor 1 (IGF-1) or bone morphogenetic protein 2 (BMP-2) complementary DNA were constructed and applied to primary human and murine chondrocytes or fibroblasts. Transgene expression was quantified by enzyme-linked immunosorbent assay. Direct injection of these vectors or AdLacZ, a reporter gene vector, into mouse knee joints was compared with the transplantation of syngeneic fibroblasts (infected ex vivo with the same vectors) with respect to virus spread, immune response, and cartilage formation by use of histologic, immunohistochemical, and molecular analyses. RESULTS: AdIGF-1 and AdBMP-2 efficiently infected all cell types tested. Human cells secreted biologically relevant levels of protein over a period of at least 28 days. Direct transfer of AdLacZ into mouse knee joints resulted in positively stained synovial tissues, whereas AdLacZ-infected fibroblasts settled on the surface of the synovial membranes. Inadvertent spread of vector DNA into the liver, lung, and spleen was identified by nested polymerase chain reaction in all mice that had received the vector directly; this rarely occurred following fibroblast-mediated gene transfer. Direct injection of AdBMP-2 induced the synthesis of new cartilage in periarticular mesenchyme, accompanied by extensive osteophyte formation. When AdBMP-2 was administered by injecting ex vivo-infected fibroblasts, cartilage formation was observed only in regions near the injected cells. AdIGF-1 treatment did not lead to morphologic changes. Importantly, fibroblast-mediated gene transfer avoided the strong immune response to adenovirus that was elicited following direct application of the vector. CONCLUSION: Our results indicate that cell-mediated gene transfer provides sufficient BMP-2 levels in the joint to induce cartilage formation while avoiding inadvertent vector spread and immune reactions.

Adenoviridae↗
PubMed2001

Highly enhanced expression of the disintegrin metalloproteinase MDC15 (metargidin) in rheumatoid synovial tissue.

OBJECTIVE: The aim of the study was to analyze the expression of the disintegrin metalloproteinase MDC15 (metargidin, or ADAM15) at the messenger RNA (mRNA) and protein levels in synovial tissue from osteoarthritis (OA) and rheumatoid arthritis (RA) patients compared with normal specimens. METHODS: Conventional immunohistochemistry and confocal laser scanning microscopy of immunofluorescently stained sections, as well as in situ hybridization experiments and reverse transcription-polymerase chain reaction were performed for analyses of MDC15 expression on normal, OA, and RA synovial tissue specimens. RESULTS: In normal synovium, MDC15 expression was detectable at a very low level. MDC15 expression was considerably increased in OA-derived tissue samples, whereas a maximum of signal intensity for MDC15 mRNA and protein was seen in the RA lining layer. The CD68+ macrophage-like synoviocytes (type A) and the CD68- fibroblast-like synoviocytes (type B) were positive for MDC15. Moreover, a very strong expression of MDC15 was also found in CD138+ plasma cells in all RA tissues as well as in OA specimens that contained areas of mononuclear cell infiltrates. CD20+ B cells and CD4+ and CD8+ T cells, however, did not exhibit expression of MDC15, either in the synovial tissue in situ or in preparations of circulating lymphocytes made from the peripheral blood of RA patients or healthy controls. CONCLUSION: Our results demonstrate high levels of MDC15 expression in macrophage-like and fibroblast-like synoviocytes as well as in plasma cells as a histologic feature most prominent in RA synovial tissue compared with normal or OA synovial tissue. This suggests a potential role of MDC15 in the pathogenesis of cartilage destruction in inflammatory joint disease.

ADAM Proteins↗
PubMed2001

Anabolic and catabolic gene expression pattern analysis in normal versus osteoarthritic cartilage using complementary DNA-array technology.

OBJECTIVE: To understand changes in gene expression levels that occur during osteoarthritic (OA) cartilage degeneration, using complementary DNA (cDNA)-array technology. METHODS: Nine normal, 6 early degenerated, and 6 late-stage OA cartilage samples of human knee joints were analyzed using the Human Cancer 1.2 cDNA array and TaqMan analysis. RESULTS: In addition to a large variability of expression levels between different patients, significant expression patterns were detectable for many genes. Cartilage types II and VI collagen were strongly expressed in late-stage specimens, reflecting the high matrix-remodeling activity of advanced OA cartilage. The increase in fibronectin expression in early degeneration suggests that fibronectin is a crucial regulator of matrix turnover activity of chondrocytes during early disease development. Of the matrix metalloproteinases (MMPs), MMP-3 appeared to be strongly expressed in normal and early degenerative cartilage and down-regulated in the late stages of disease. This indicates that other degradation pathways might be more important in late stages of cartilage degeneration, involving other enzymes, such as MMP-2 and MMP-11, both of which were up-regulated in late-stage disease. MMP-11 was up-regulated in OA chondrocytes and, interestingly, also in the early-stage samples. Neither MMP-1 nor MMP-8 was detectable, and MMP-13 and MMP-2 were significantly detectable only in late-stage specimens, suggesting that early stages are characterized more by degradation of other matrix components, such as aggrecan and other noncollagenous molecules, than by degradation of type II collagen fibers. CONCLUSION: This investigation allowed us to identify gene expression profiles of the disease process and to get new insights into disease mechanisms, for example, to develop a picture of matrix proteinases that are differentially involved in different phases of the disease process.

Adult↗
PubMed2001

Tenascin: a sensitive and specific diagnostic marker of minimal collagenous colitis.

Collagenous colitis is a rare cause of chronic watery diarrhea. In this condition, endoscopic findings are usually normal. Currently, the diagnosis relies on the histological presence of thick subepithelial bands of collagen deposits and an inflammatory infiltrate within the mucosa. However, these subepithelial bands may be developed only focally and may be too subtle to allow a definitive diagnosis upon routine hematoxylin and eosin (HE) and van Gieson's stainings. Recently, we and others were able to show a prominent staining of tenascin and type-VI collagen in the subepithelial band-like structures. In this study, we tested the diagnostic value of tenascin staining and type-VI collagen immunolocalization for the identification of collagenous colitis and compared it with conventional histology and histochemical detection of collagens. The analysis was based on 434 biopsy specimens of collagenous colitis, other forms of colitis, and normal mucosa. We were able to show that the immunohistochemical detection of increased amounts of tenascin, selectively in the subepithelial zone, is a specific test for collagenous colitis, with a sensitivity superior to conventional histological and histochemical detection, especially in minimal collagenous colitis (P<0.001). Of note, tenascin staining also allows the diagnosis of collagenous colitis in biopsies obtained only from the rectum and sigmoid colon, thus avoiding the need for colonoscopic investigations. Tenascin immunostaining is a simple and safe tool to complement conventional histological diagnostics in clinically and histopathologically unclear cases of diarrhea.

Adolescent↗
PubMed2001

Matrix gene expression analysis and cellular phenotyping in chordoma reveals focal differentiation pattern of neoplastic cells mimicking nucleus pulposus development.

Chordoma is the fourth most common malignant primary neoplasm of the skeleton and almost the only one showing a real epithelial phenotype. Besides classic chordoma, so-called chondroid chordoma was described as a specific entity showing cartilage-like tissue within chordomatoid structures. However, since its first description, strongly conflicting results have been reported about the existence of chondroid chordoma and several studies suggested chondroid chordomas being in fact low-grade conventional chondrosarcomas. In the present study, we used cytoprotein expression profiling and molecular in situ localization techniques of marker gene products indicative of developmental phenotypes of chondrocytes to elucidate origin and biology of chondroid chordoma. We were able to demonstrate the chondrogenic potential of chordomas irrespectively of the appearance of overt cartilage formation by identifying the multifocal expression of type II collagen, the main marker of chondrocytic differentiation. Additionally, the cartilage-typical large aggregating proteoglycan aggrecan was present throughout all chordomas and, thus, a very characteristic gene product and marker of these neoplasms. Biochemical matrix composition and cell differentiation pattern analysis showed a high resemblance of classic chordomas and in chordoid areas of chondroid chordomas to the fetal chorda dorsalis, whereas chondroid areas of chondroid chordomas showed features similar to adult nucleus pulposus. This demonstrates on the cell function level the chondrocytic differentiation potential of neoplastic chordoid cells as a characteristic facet of chordomas, mimicking fetal vertebral development, ie, the transition of the chorda dorsalis to the nucleus pulposus. Our study firmly establishes a focal real chondrocytic phenotype of neoplastic cells in chordomas. Chondroid chordoma is neither a low-grade chondrosarcoma nor a misnomer as discussed previously.

Aggrecans↗