Constitutive expression of tenascin in T-dependent zones of human lymphoid tissues.

Tenascin is a major extracellular matrix glycoprotein that can interfere with the action of fibronectin by inhibiting cell adhesion and spreading. Although tenascin is able to exert important immunomodulatory activities on T and B cells and macrophages, little is known about its distribution in different lymphohemopoietic tissues. In this study we have analyzed tenascin immunoreactivity on cryostat and paraffin sections of normal and pathological lymphoid tissues using two different monoclonal antibodies. We demonstrated strong tenascin expression in all peripheral lymphoid tissues, whereas it was barely detectable in the thymus and in bone marrow. In reactive lymph nodes, tenascin was mainly found in T-dependent zones, forming a variably close-woven reticular network corresponding to fibroblastic reticulum cells and blood vessels basal laminae, showing a partial co-localization with fibronectin. In B-dependent zones, tenascin was restricted to blood vessels. Using double-marker analysis, we performed a thorough study comparing tenascin expression in different compartments of lymphoid microenvironments. Tenascin network appeared much thicker in chronically stimulated tissues, where CD4+ lymphocytes with "memory" phenotype (CD45RO+/CD45RA-) were predominant, and at sites of ongoing inflammation. In particular, a striking increase of tenascin was observed in sarcoid lymph node, as well as in myasthenic hyperplastic thymuses. In addition, tenascin can be abnormally synthesized in tissue involved by various types of lymphomas, including Hodgkin's disease and hairy cell leukemia.     

Tenascin in reactive lymph nodes and in malignant lymphomas.

Tenascin is an extracellular matrix protein which accumulates in the stroma of various malignant and some benign neoplasms. This has been verified in several immunohistochemical studies. The distribution of tenascin immunoreactivity in lymphatic tissues and neoplasias, however, has not been thoroughly studied. In this investigation we analyzed tenascin immunoreactivity in several benign and malignant lymphatic lesions, including both Hodgkin's and non-Hodgkin's lymphomas. In benign lymph nodes, faint reticular immunoreactivity could be observed in the lymphatic tissue. In benign reactive hyperplasias, a stronger reticular pattern of tenascin immunoreactivity was observed in the interfollicular and medullary areas, while the lymphoid follicles contained only a few positive fibers. A similar immunoreactivity was observed in malignant follicular lymphomas. In diffuse lymphomas, a diffuse meshwork of positively stained fibers was seen. This was also the case for the three cases of Hodgkin's disease of the lymphocyte-predominance nodular subtype. There was no difference in the intensity of the immunoreactivity between benign and malignant disorders. However, in Hodgkin's disease of the nodular sclerosis and lymphocyte-depletion subtypes, a much more pronounced immunoreactivity could be observed in the fibrous septa and the cords. This suggests that the tumor cells are possibly capable of synthesizing growth factors which stimulate fibroblasts to synthesize tenascin. The results indicate that tenascin does not accumulate in the stroma of malignant lymphoid neoplasms with the exclusion of some subtypes of Hodgkin's disease. The distribution of tenascin immunoreactivity in lymphatic tissue is similar to that of the reticular fibers suggesting that the molecules are associated with these structures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of Matrix Proteins in Perichondrium and Periosteum During the Incorporation of Meckel's Cartilage into Ossifying Mandible in Midterm Human Fetuses: An Immunohistochemical Study

Immunohistochemical localization of versican and tenascin‐C were performed; the periosteum of ossifying mandible and the perichondrium of Meckel's cartilage, of vertebral cartilage, and of mandibular condylar cartilage were examined in midterm human fetuses. Versican immunoreactivity was restricted and evident only in perichondrium of Meckel's cartilage and vertebral cartilage; conversely, tenascin‐C immunoreactivity was only evident in periosteum. Therefore, versican and tenascin‐C can be used as molecular markers for human fetal perichondrium and fetal periosteum, respectively. Meckel's cartilage underwent endochondral ossification when it was incorporated into the ossifying mandible at the deciduous lateral incisor region. Versican immunoreactivity in the perichondrium gradually became weak toward the anterior primary bone marrow. Tenascin‐C immunoreactivity in the primary bone marrow was also weak, but tenascin‐C positive areas did not overlap with versican‐positive areas; therefore, degradation of the perichondrium probably progressed slowly. Meanwhile, versican‐positive perichondrium and tenascin‐C‐positive periosteum around the bone collar in vertebral cartilage were clearly discriminated. Therefore, the degradation of Meckel's cartilage perichondrium during endochondral ossification occurred at a different rate than did degradation of vertebral cartilage perichondrium. Additionally, the perichondrium of mandibular condylar cartilage showed tenascin‐C immunoreactivity, but not versican immunoreactivity. That perichondrium of mandibular condylar cartilage has immunoreactivity characteristic of other periosteum tissues may indicate that this cartilage is actually distinct from primary cartilage and representative of secondary cartilage. Anat Rec, 297:1208–1217, 2014. © 2014 Wiley Periodicals, Inc.     

Tenascin in human papillomavirus associated lesions of the uterine cervix.

The immunohistochemical expression of tenascin was studied in 80 morphologically diagnosed condylomas and cervical intraepithelial neoplasia (CIN) lesions. The results were compared with the human papillomavirus (HPV) DNA subtype, which was determined by HPV dot blot and in situ hybridisation. Tenascin mRNA synthesis was also determined in 10 selected cases by in situ hybridisation. No statistically significant association was found between tenascin expression and the degree of dysplasia or the HPV subtype. There was, however, a strong correlation between the extent of tenascin immunoreactivity and the degree of inflammation. Synthesis of tenascin mRNA was detected in basal keratinocytes and in fibroblasts by in situ hybridisation. The lack of association between the grade of CIN and tenascin expression precludes its use as a marker of premalignancy in CIN.     

TENASCIN AND FIBRONECTIN EXPRESSION IN HEALING HUMAN MYOCARDIAL SCARS

Fibronectin and tenascin are matrix proteins known to be present in early experimental wound healing. As only limited data are available regarding early matrix changes in human myocardial infarction, the presence of tenascin and fibronectin was studied in human myocardial infarctions of different post-infarction times (6 h to 17 years), using immunohistochemistry. In normal myocardium, fibronectin immunostaining was found in the subendothelial space in vessels. Tenascin was not present in normal myocardium. While fibronectin was demonstrated in the ischaemic cardiomyocytes within 1 day, tenascin was found 4–6 days post-infarction and was located at the margin of the area of infarction. Tenascin expression then shifted from the margin to the centre of the area of infarction, where it could be found 2–3 weeks post-infarction. More than 4 weeks post-infarction, the scar tissue consisted of collagen fibres, with sparse (myo)fibroblasts. By that time, both tenascin and fibronectin expression had disappeared. Another interesting observation in this study was the presence of tenascin, but not fibronectin, surrounding vacuolated glycogen-rich cells, or so-called hibernating cardiomyocytes.     

Physiology: Distribution of tenascin in normal cycling human ovary

Tenascin is an extracellular matrix glycoprotein, which hasbeen reported to be involved in parenchymal—mesenchymalinteractions during morphogenesis, wound healing, and carcinogenesis.Tenascin immunolocalization was performed in 51 specimens ofmorphologically normal human ovaries by using a specific monoclonalantibody against purified human fibroblast tenascin. In preovulatoryfollicles, no significant immunoreactivity was detected. Infunctioning corpora lutea, immunoreactivity was present as afine border around the periphery. In association with the involutionof the corpora lutea, marked diffuse tenascin immunostainingin the intercellular space was observed. These data raise thequestion of whether tenascin may be involved in luteolysis andmay play an important role in the ovarian cycle by regulatingthe involution of corpora lutea.     

Tenascin-C and human tendon degeneration.

We investigated the distribution of tenascin in supraspinatus tendons to determine whether an alteration in tenascin expression was associated with human tendon degeneration. Tenascin was present in all of the tendons studied, although with two distinct patterns of expression. First, tenascin was associated with organized, fibrous regions of the tendon matrix that were typical of the normal tendon structure. This distribution is consistent with a role for tenascin in collagen fibril organization, perhaps maintaining the interface between fibrils and adjacent structures. Second, although tenascin was generally absent from poorly organized matrix in degenerate tendons, it was strongly associated with some rounded cells in disorganized fibrocartilaginous regions that were more abundant in pathological specimens. Tenascin was also found around infiltrating blood vessels, with more intense staining associated with a mononuclear cell infiltrate. Western blotting of tendon extracts showed differences in tenascin isoform expression, with only the small (200-kd) tenascin isoform found in normal tendons. Degenerate tendons also expressed the 300-kd isoform, consistent with a role for the larger tenascin isoform in tendon disease, potentially stimulating tenocyte proliferation, cell rounding, and fibrocartilaginous change. Proteolytic fragments of tenascin were detected but only in ruptured tendons, an indication of matrix remodeling in degenerate tendons, with fragment sizes consistent with the activity of matrix metalloproteinase enzymes.     

Tenascin in salivary gland tumours

Summary The distribution of tenascin immunoreactivity was analysed in salivary gland tissue and in various benign and malignant tumours of the salivary gland. In the non-neoplastic tissue, tenascin was seen in the areas of basement membranes of the ductal epithelium. No immunoreactivity could be observed in the serous or mucous glands. In pleomorphic adenomas, tenascin immunoreactivity could be seen in the stromal compartment. It was more pronounced in the dense stromal areas and chondroid elements than in the myxoid area. In Warthin's tumours, strong tenascin immunoreactivity could be observed in the basement membrane zone of the epithelial component. In the lymphatic component, faint reticular staining could be seen. In adenoid cystic carcinomas, acinic cell tumours and mucoepidermoid carcinomas, tenascin showed a linear stromal distribution. No intracytoplasmic immunoreactivity could be seen in any of the cases. The widespread tenascin positivity in salivary gland tumours suggests that tenascin may play a role in the induction and progression of salivary gland tumours, presumably by interfering with the normal parenchymal-mesenchymal interaction.     

Tenascin C expression is upregulated in pancreatic cancer and correlates with differentiation

BACKGROUND: Tenascin C is a large, hexameric, extracellular matrix protein that is present during embryonic development but essentially absent in adult tissues. It is involved in remodelling processes, such as wound healing and tumour development. Tissue expression of tenascin C correlates with prognosis in colorectal, cervical, and breast cancer and in carcinoma of the papilla of Vater. AIM: To study the expression of tenascin C in pancreatic cancer and to compare the staining results with the patients' clinicopathological data. MATERIAL AND METHODS: Formalin fixed, paraffin wax embedded specimens from 146 patients with pancreatic adenocarcinoma were stained with an anti-tenascin C monoclonal antibody. RESULTS: Tenascin C immunoreactivity was seen in most samples of pancreatic carcinoma: staining was weak in 72 (49%), moderate in 52 (36%), strong in 10 (7%), and negative in 12 (8%) samples. Tenascin C expression correlated with age (< or = 66 v >66 years) and poor differentiation (grades 1-2 v 3). There was no correlation between tenascin C expression and survival, clinical stage, tumour size, nodal status, distant metastasis, tumour location, or sex. CONCLUSION: Tenascin C expression was increased in most pancreatic carcinomas, but contrary to the results in other cancers, it is not a prognostic factor in pancreatic cancer.     

Comparison of the distribution patterns of tenascin and alkaline phosphatase in developing teeth, cartilage, and bone of rats and mice.

Tenascin is a glycoprotein of the extracellular matrix, which has been associated with differentiation of hard tissue forming cells. Alkaline phosphatase (AP) is involved in calcification, and it has also been suggested to function in cell differentiation. We have compared the distributions of tenascin and AP in the developing skull and teeth of embryonic and growing rats and mice. Tenascin was localized by immuno-Peroxidase and AP by enzyme histochemical staining of tissue sections. Both tenascin and AP were largely restricted to bone, cartilage, and teeth. In cartilage, tenascin was expressed in the perichondrium, whereas AP activity was detected only in the hypertrophic cartilage. In growing intramembranous bone, tenascin and AP were expressed in the periosteum and endosteum. AP activity was restricted to the inner layer of the periosteum, whereas tenascin expression extended to the more superficial layers. In bud-staged teeth tenascin but no AP activity was localized in the condensing mesenchymal cells around the epithelial bud. At the bell stage both tenascin and AP activity were localized in the cuspal mesenchyme, and the intensity of staining decreased towards the cervical region. In summary, tenascin was present at all sites of AP activity except in the epithelial cells of the enamel organ and the hypertrophic cartilage of the mandibular condyle. In mesenchymal tissues tenascin was more widely distributed than AP. It can be suggested that tenascin has functions at earlier stages of hard tissue formation than AP.     

Comparison of the distribution patterns of tenascin and alkaline phosphatase in developing teeth,cartilage, and bone of rats and mice

Tenascin is a glycoprotein of the extracellular matrix, which has been associated with differentiation of hard tissue forming cells. Alkaline phosphatase (AP) is involved in calcification, and it has also been suggested to function in cell differentiation. We have compared the distributions of tenascin and AP in the developing skull and teeth of embryonic and growing rats and mice. Tenascin was localized by immuno-Peroxidase and AP by enzyme histochemical staining of tissue sections. Both tenascin and AP were largely restricted to bone, cartilage, and teeth. In cartilage, tenascin was expressed in the perichondrium, whereas AP activity was detected only in the hypertrophic cartilage. In growing intramembranous bone, tenascin and AP were expressed in the periosteum and endosteum. AP activity was restricted to the inner layer of the periosteum, whereas tenascin expression extended to the more superficial layers. In bud-staged teeth tenascin but no AP activity was localized in the condensing mesenchymal cells around the epithelial bud. At the bell stage both tenascin and AP activity were localized in the cuspal mesenchyme, and the intensity of staining decreased towards the cervical region. In summary, tenascin was present at all sites of AP activity except in the epithelial cells of the enamel organ and the hypertrophic cartilage of the mandibular condyle. In mesenchymal tissues tenascin was more widely distributed than AP. It can be suggested that tenascin has functions at earlier stages of hard tissue formation than AP.     

Differential distribution of tenascin in the normal, hyperplastic, and neoplastic breast.

We studied by immunohistochemistry the distribution of tenascin with the monoclonal antibody 100EB2, and compared it with that of laminin in breast tissue samples from fetal, adult resting, lactating, and aging parenchyma, variants of fibrocystic disease, fibroadenomas, cystosarcoma phylloides, and ductal and lobular carcinomas. Monoclonal antibodies were applied to cryosections by the avidin-biotin-complex method; selected samples were studied by double immunofluorescence, and by Western blot analysis. In adult resting and aging breasts, tenascin immunoreactivity was noted in the periductal and periacinar stromal regions as thin irregular bands; in the lactating breast, broader periductal bands were observed. In these samples, laminin immunoreactivity was a single continuous line around ducts, acini, and vessels. In fetal breasts, tenascin appeared as thick periductal bands, whereas laminin remained as a delicate single line. In FCD, tenascin increased around ducts showing hyperplasia, papillomas and apocrine metaplasia, whereas laminin retained its delicate linear pattern. Similar patterns were seen in fibroadenomas and cystosarcoma phylloides with variable tenascin reactivity in the stroma beyond the ducts. Tenascin immunoreactivity was markedly increased around ducts containing in situ carcinoma appearing as broad bands, whereas that of laminin showed a linear, frequently discontinuous appearance. Prominent stromal tenascin immunoreactivity was seen in infiltrating ductal and lobular carcinomas, whereas laminin was virtually absent save for scattered lines. The abundance of tenascin in the carcinomatous stroma contrasted with its scarcity in the non-neoplastic stromal regions. By Western blotting, both chains of tenascin with molecular weights 250,000 and 180,000 were shown in ductal and lobular carcinomas as well as in normal breast. Tenascin immunoreactivity was noted in the periepithelial stromal regions of adult resting and aging breast ducts and acini. The amount of tenascin was moderately enhanced in certain physiologic conditions (fetal growth, gestation), as well as hyperplasias, dysplasias (fibrocystic disease) and benign tumors, whereas it was markedly enhanced in intraductal and infiltrating carcinomas. During fetal mammary development, adult physiologic and pathologic hyperplasias, and in carcinomas, the increasing tenascin reactivity contrasted with the stable or decreasing laminin reactivity.     

Tenascin expression in intraepithelial neoplasia and invasive carcinoma of the uterine cervix

OBJECTIVE: To determine whether the expression of the matrix protein tenascin (TN) is of diagnostic or prognostic value in cervical intraepithelial neoplasia (CIN). DESIGN: Tenascin expression was evaluated in 75 formalin-fixed, paraffin-embedded biopsy and surgical specimens of the uterine cervix. Specimens included 15 low-grade squamous neoplastic lesions (CIN I), 30 high-grade squamous neoplastic lesions (CIN II and CIN III), 5 microinvasive carcinomas, and 15 invasive squamous carcinomas. Five normal cervices and 5 examples of cervicitis were used as controls. Expression of TN was studied by immunohistochemistry with a monoclonal mouse anti-human tenascin antibody. Tenascin expression in the basement membrane and in the stroma was arbitrarily graded as normal or slightly, moderately, or markedly increased. RESULTS: In the normal cervix, TN formed a thin band along the basement membrane of the squamous epithelium, except for the transformation zone, where the bands splintered and delicate TN fibers were present in the adjacent stroma. In cervicitis, TN bands were splintered in the basement membrane and the protein was weakly expressed in the stroma infiltrated by inflammatory cells. In the 45 CIN lesions, regardless of grade, the TN bands in the basement membrane were slightly (25 cases) or moderately (20 cases) increased. In CIN lesions with chronic stromal inflammation, a slight increase in stromal staining was observed, similar to the findings in cervicitis. In microinvasive and frankly invasive squamous cell carcinomas, TN expression was markedly increased in the basement membrane and in the stroma surrounding the invasive nests of cancer cells. CONCLUSION: Tenascin expression may be of value in the assessment of early stromal invasion in cancer of the uterine cervix. Tenascin expression is of no value in distinguishing various grades of CIN and, therefore, is not a predictor of future behavior.     

Macrophages (phagocytic-histiocytic reticular cells) in reactive-inflammatory lesions of the bone marrow and in myelodysplastic syndromes (MDS). An immunohistochemical and morphometric study by use of a new monoclonal antibody (PG-M1).

An immunohistochemical and morphometric study was performed on trephine biopsies of the bone marrow in 52 patients (28 males/24 females; age 68 years) with various subtypes of myelodysplastic syndromes (MDS) to determine the number of macrophages (phagocytic-histiocytic reticular cells). Quantifications included the haemosiderin-storing subpopulation (Prussian-blue reaction) of this lineage as well as the iron-free compartment. The latter was identified by a new monoclonal antibody (PG-M1) which is specifically directed against histiocytic reticular cells. Bone marrow specimens of individuals without haematological disorders and those showing reactive lesions served as controls. In comparison with the normal bone marrow and inflammatory changes (i.e. rheumatoid arthritis) 23 of the 52 patients with MDS revealed a significant increase in macrophages. This increase encompassed not only the iron-laden subpopulation but also the total number of phagocytic reticular cells. Accumulation of macrophages in MDS was speculated to be due to a premature and enforced degradation of dysplastic cell elements leading to phagocytosis of haemosiderin and debris material. Moreover, cells of the monocyte-macrophage system could be involved in the complex pathomechanism of fibrillogenesis, since in a considerable percentage of patients with MDS, an increase in reticulin (argyrophilic) fibres was noticeable. Our finding of an expansion of the macrophage compartment in about half of the patients with MDS is in keeping with results of cell culture studies on colony formation of granulocyte-macrophage precursors (CFU-GM).     

Tenascin expression in normal, hyperplastic, dysplastic and neoplastic canine mammary tissues

Mammary tumours are the most common neoplasias of female dogs and may have a complex histological pattern with both epithelial and spindle cells participating in the transformation process. A frequent feature of these tumours is chondroid or bone metaplasia of the extracellular matrix, which mainly occurs in areas of proliferated spindle-shaped cells, probably of myoepithelial origin. The present study evaluates immunohistochemically the expression of tenascin in 186 surgical samples of canine mammary tissues, ranging from normality to neoplasia. Tenascin was present in all mammary tissues studied, with an increased expression in remodelling situations and in neoplastic lesions. Basement membrane was the most frequently labelled structure, but stromal tissue was more often and widely labelled in neoplastic lesions. The extracellular matrix was positive in solid and anaplastic carcinomas as well as in spindle cell proliferation areas. Tenascin expression in extracellular matrix was also abundant in areas of initial chondroid metaplasia and, with variable extension, in almost all cartilage islands of mixed tumours. In well differentiated secretory areas only apical granules of luminal cells were positive, suggesting a different pattern of tenascin expression during secretory differentiation. The digestion of chondroitin sulphate significantly improved the labelling for tenascin when a co-expression of these two molecules was present. Although our results suggest that tenascin cannot be used as a marker of transformation or of malignancy in canine mammary oncology, it is clear that this molecule plays an important role in proliferation and differentiation processes in the canine mammary gland.     

LAT (linker for activation of T cells): a useful marker for megakaryocyte evaluation on bone marrow biopsies

Detection of atypical megakaryocytes in bone marrow biopsies, especially in cases of myelodysplastic syndromes (MDS), chronic myeloproliferative disorders (CMPD) and acute leukemias, is facilitated by staining for markers such as Ulex europaeus agglutinin (UEA)-J, CD31, CD61 and von Willebrand factor (VWF), the latter being considered the most sensitive. Recently, LAT (linker for activation of T cells), a molecule involved in T-cell activation and platelet aggregation, was found to be expressed by megakaryocytes and platelets in tissue sections. We compared VWF and LAT immunoreactivity on megakaryocytes in 64 bone marrow biopsies from 12 normal controls (NC), and from patients with MDS (n=18), CMPD (n=21) and acute megakaryocytic leukemia (AML-M7, n=13). Immunostaining was performed on paraffin sections with polyclonal antibodies against VWF and LAT. Immunoreactivity was evaluated by counting positive megakaryocytes in 10 high-power fields, and values were compared using Student's t test for paired data. Both VWF and LAT predominantly stained the cytoplasm of megakaryocytes, although LAT was also recognizable on the cell membrane. In most biopsies, the immunoreactivity of the two antibodies was quite similar. No significant differences were noticed between the mean values of VWF+ and LAT+ megakaryocytes. However, in 22 cases (5 NC; 5 MDS; 6 CMPD; 6 AML-M7), the number of LAT+ megakaryocytes was at least 30% higher than VWF+cells, while in 3 cases opposite findings were found. In 3 AML-M7 cases, anti-LAT antibodies stained numerous megakaryocytes, but anti-VWF staining was practically negative; in another 5 AML-M7 cases, anti-LAT labeling was much stronger than anti-VWF staining. LAT represents a useful immunohistochemical marker for megakaryocytes in normal and pathological conditions. It seems to be expressed by megakaryocytes more than VWF in most cases and, particularly, in conditions associated with poorly differentiated megakaryocytes, such as acute megakaryocytic leukemias. The use of LAT staining should be recommended in association with other megakaryocyte markers in the study of bone marrow biopsies in cases of hematopoietic disorders.     

Tenascin expression and angiogenesis in breast cancers

The expression and the distribution of tenascin as well as the extent of blood vessel formation (angiogenesis) were investigated in 70 invasive human breast carcinomas. Formalin-fixed, paraffin-embedded specimens were stained with monoclonal antibody against tenascin-C (DAKO and Biogenex). Anti-CD31 antibody (Biogenex), an acknowledged marker of stromal angiogenesis, was used to detect endothelial cells. Tenascin immunostaining was positive in the tumours around the persisting normal ducts, around tumour-cell nests, in the neostroma, in some tumour cells, and it was found in or around vascular channels. Tumour vascularity was assessed by quantitative vascular grading (Chalkley point count) and was related to the localization and intensity of tenascin immunoreactivity. 19 tumours (27.1%) were scored as low, 35 (50%) as medium, and 16 (22.9%) as having a high vascular grade. The positive correlation between the vascular grade and the tenascin immunopositivity in tumour stroma was observed. Our results suggest that tenascin expression may be associated with endothelial cell activation and may play an important role in tumour angiogenesis.     

Pleomorphic adenoma and carcinoma ex pleomorphic adenoma: immunohistochemical demonstration of the association between tenascin expression and malignancy

AIMS: To investigate tenascin expression in salivary gland tumours. Tenascin is a matricellular protein that has been studied in several tumour types. Its expression has been correlated with tumour morphogenesis as well as with local invasiveness and tumour metastatic behaviour. METHODS AND RESULTS: The distribution pattern of tenascin in a series of 63 pleomorphic adenomas (PA) and 20 carcinomas ex- pleomorphic adenoma (Ca ex PA) was studied immunohistochemically. Ten normal adult salivary glands were used as controls. Tenascin surrounded the excretory ducts of normal adult salivary gland tissue. It was absent in the basement membrane compartment of both benign and malignant mixed tumours. In the interstitial compartment of the extracellular matrix, the fibro-hyaline type expressed tenascin in a statistically significantly (P < 0.001) lower number of PA cases (25%) in comparison with both malignant and benign areas of Ca ex PA (75% and 90%, respectively). In the Ca ex PA group, a statistically significantly difference (P < 0.001) was found in the frequency of tenascin deposits around aggregates of neoplastic cells between metastasizing (73%) and non-metastasizing neoplasms (0%). CONCLUSIONS: These findings strongly support the hypothesis that tenascin deposition is involved in the mechanisms of malignant transformation of pleomorphic adenomas into carcinomas as well as being associated with clinical disease progression.     

Colocalization of tenascin with versican, a hyaluronate-binding chondroitin sulfate proteoglycan

Rabbit antisera against tenascin, a large extracellular matrix protein, in conjunction with monoclonal antibodies of mouse origin against versican, a large hyaluronate-binding proteoglycan, were used to make a comparative study of the distribution of the two antigens in the same cryostat sections by double immunofluorescence. In the central nervous system, tenascin was invariably associated with versican, but the reverse was not true, in that versican was also found where tenascin was not detectable, particularly in gray matter. There were major species differences in the distribution of tenascin in the central nervous system. In the cow, tenascin was found in cerebral and spinal cord white matter and in the granule cell layer of the cerebellum. In the human brain, tenascin was found in cerebral white matter but not in the cerebellum. In the rat, tenascin was mainly confined to brain periventricular layer and spinal cord white matter. During the development of the cerebellum of the rat, the tenascin immunoreactivity decreased, and a lower molecular weight band appeared (J1-160/180/restrictin?) and persisted throughout adulthood. Tenascin expression was a relatively late event in the development of the rat central nervous system, immunoreactivity being first observed after birth. In the rat embryo, tenascin was found to co-localize with versican in precartilaginous mesenchyme and in connective tissue underlying epithelia. The colocalization of versican with tenascin suggests that versican may be the tenascin (cytotactin)-associated proteoglycan reported in the literature.