Different fibronectin (FN) isoforms are generated by the alternative splicing of the primary FN transcript. We previously demonstrated that the isoform containing the extra domain B sequence of ...fibronectin (B-FN), a complete type-III-homology repeat, is a marker of angiogenesis that accumulates around neovasculature only during angiogenic processes. We produced a single-chain human recombinant antibody (scFv), L19, which reacts specifically with B-FN and selectively targets tumor vasculature
in vivo
. We used this scFv and an antibody against a pan-endothelial marker (Factor VIII) in a double-staining procedure on specimens of low- and high-grade astrocytomas to determine the percentage of B-FN-positive vessels, (denominating the resulting value angiogenic index AI). Compared to vascular density and proliferative activity (evaluated using antibodies to Factor VIII and Ki67, respectively), AI correlated better with tumor grade (1.6 ± 2.6% and 92.0 ± 8.7% of B-FN-positive vessels in low- and high-grade astrocytomas, respectively) and was a more precise diagnostic tool than either of the two conventional methods. In fact, discriminating analysis using these three parameters showed that only AI accurately classified 100% of the cases studied, compared to 64% and 89% correctly diagnosed by vascular density and of proliferating cells, respectively.
Fibronectins (FNs), adhesive glycoproteins mainly expressed in the extracellular matrix, are polymorphic molecules whose various isoforms are dependent on alternative splicing patterns. The isoform ...containing the ED-B sequence and occurring in foetal and neoplastic tissues (oncofoetal or B+FN) has been previously recognized as a marker for angiogenesis. The distribution of this isoform was analyzed in a consecutive series of 134 surgically obtained intracranial meningiomas, using specific monoclonal antibodies. Oncofoetal FN was found to be widely distributed in the vessels of anaplastic meningiomas, with its expression being restricted in the vasculature of the typical subtypes. and absent in the neighbouring cerebral tissue. The ubiquitous vascular expression of B+FN in meningiomatous malignancies might provide a potential target for the in vivo delivery of angiosuppressive agents.
Somatostatin receptors (SSTRs) have been detected in many normal and malignant tissues. This wide expression has been used for diagnostic, prognostic and therapeutic purposes. Five SSTR subtypes ...(SSTR 1-5) have been identified whose activation is responsible for the signal transduction through many different intracellular pathways. In the present study the expression of SSTR mRNA was determined by reverse-transcriptase (RT)-PCR in 42 meningiomas. About 88% of the tumors analyzed (37/42) were positive for at least one of the five SSTR subtypes displaying a variable pattern of expression of the different SSTR subtypes. SSTRI and SSTR2 were the most frequently mRNA detected (69% and 79% of the sample analyzed, respectively). The other subtypes were found in the 43%, 33% and 33% of cases for SSTR3, SSTR4 and SSTR5, respectively. In 22, out of 42 patients (52%) three or more SSTRs were detected. The expression of the different SSTR subtypes did not correlate with the expression of bcl-2 (apoptosis-associated protein) and MIB-1 (a proliferation marker), assessed by immunohistochemistry in a series of 34 tumor samples, while a correlation between the expression of SSTR3 and p53 was observed (p = 0.08). To evaluate a possible role of SSTR in the control of human meningioma cell proliferation, seven primary cell cultures obtained from fresh meningioma surgical tissues, were analyzed for their proliferative behavior by MTT assay and for their response to SST by 3H-thymidine incorporation. In four out of six tumors (in one case no SSTR were detected) the treatment with SST caused a significant inhibition of DNA synthesis induced by the tumor-promoter phorbol myristate acetate. The evidence of the expression of SSTRs, mainly of SSTR2, in this series of specimens we analyzed altogether with in vitro antiproliferative effects of SST may open interesting perspectives for the diagnosis and the therapy of meningiomas.
According to the previous characterisations the BC-1 mAb and the TN-11 Ab fragments are specific for isoforms occurring almost exclusively in fetal tissues and in tumours, with the recognised TN ...isoform being typically associated with anaplastic gliomas (table).
Tenascin-C exists in several polymorphic isoforms due to alternative splicing of nine fibronectin-like type III repeats. Large Tenascin-C isoforms are present in almost all normal adult tissues but ...are upregulated in fetal, regenerating, and neoplastic tissues. Here, we report a human antibody fragment, TN11, derived from a phage library with high affinity for the spliced repeat C and demonstrate that this repeat is undetectable in normal adult tissues, barely detectable or undetectable in breast, lung and gastric carcinomas, meningioma, and low grade astrocytoma, but extremely abundant in high grade astrocytoma (grade III and glioblastoma), especially around vascular structures and proliferating cells. The antibody appears to have potential for development of a therapeutic agent for patients with high grade astrocytoma.
Different fibronectin (FN) isoforms are generated by the alternative splicing of 3 regions (ED-A, ED-B and IIICS) of the primary transcript. The FN isoform containing the ED-B sequence, a complete ...type-III-homology repeat, while having extremely restricted distribution in normal adult tissues, reveals high expression in fetal and tumor tissues. Using the monoclonal antibody (MAb) BC-I, specific for the FN isoform containing the ED-B sequence (B+.FN), we demonstrated here, using immunohistochemical techniques, that while this FN isoform is undetectable in mature vessels, it is highly expressed during angiogenesis both in neoplastic and in normal tissues, as in the case of the functional layer of endometrium during the proliferative phase. B+.FN is thus a marker for the formation of new vessels, and the BC-I MAb may be a useful reagent for evaluating the level of the angiogenetic process in different neoplasms.
In six out of the 10 anaplastic meningiomas, definite endothelial staining occurred in more than 75% of the larger vessels. Besides the vascular endothelium, either the stroma or the tumorous cells ...showed some staining, although highly variable, in individual tumours, both in intensity and in distribution.
Intraventricular location of meningiomas is impressively higher in childhood and adolescence than in adult patients, respectively 15 to 22% versus 0.2 to 4%. However, location of this tumor within ...the third ventricle is extremely rare in the pediatric population, since, as far as we know, 17 cases have been reported so far. A case of meningioma of the third ventricle in a 9-year-old boy and its clinical and pathological finding are discussed.
Using a monoclonal antibody specific for human tenascin (TN), 180 intracranial growths were immunohistochemically studied. In 69 cases of meningioma, neoplastic cells were negative, with some ...positivity being observed only in the perivascular and the supporting stroma, especially in anaplastic meningiomas. In 57 cases of glioma different degrees of reactivity occurred in both the cellular conglomerates and the stromal components of the tumours. A higher variability in reactivity was observed in anaplastic astrocytomas and glioblastomas. The most constant finding of the study was the staining of the stroma, which was observed in all types of growths, including metastasis, abscess and tuberculoma. The results are consistent with the hypothesis that tenascin is a stromal marker rather than a true marker of malignant tumours. The heterogeneous distribution of TN in anaplastic gliomas may be a factor in the variable response to treatment with radiolabelled anti-TN monoclonal antibodies.
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