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An elastofibroma is a benign and rare fibrous lesion that most commonly occurs in the periscapular region. A gastrointestinal elastofibroma is extremely rare. In the present study, six cases of elastofibromas including a case in the stomach were evaluated. The gastric case revealed widely distributed lesions in the submucosal layer with perivascular fibrotic lesions (PVFLs) and some PVFLs were distributed to the skip lesions of elastofibroma. These PVFLs were also observed in all five periscapular cases and invariably contained elastic fibers which showed various degree of maturation. CD34-positive stromal cells were observed not only in elastofibromas but also in PVFLs in each case. These findings suggested the possibility of the PVFLs were the primary lesions of elastofibroma and their vascular-centric development. The percentage of the CD105-positive vessels in elastofibroma group was significantly higher than in the control group. This result indicates active neovascularization in elastofibromas.

In the present study, we analyzed tumor associated stromal remodeling with special respect to SPARC (secreted protein acid rich in cysteine) expression. 25 invasive ductal carcinomas of the breast and corresponding tumor-free breast tissue were studied immunohistochemically (CD34, alpha-SMA, SPARC and TGFbeta-R1). Tumor associated stroma was characterized by a loss of CD34 expression, paralleled by a gain in alpha-SMA. While SPARC expression was virtually absent from normal stromal cells in the tumor stroma, strong cytoplasmic SPARC reactivity was found in the majority of stromal cells. The TGFbeta-R1 also showed stronger expression in the tumor stroma compared to that of the normal breast. Stromal response to antecedent core needle biopsy was similar to that observed in the tumor stroma. We conclude that SPARC overexpression is a constant and functionally important feature of invasive ductal carcinomas, since SPARC mediates stromal de-adhesion crucial for local tumor invasion and systemic spread, respectively. When considering changes of the stromal phenotype (normal: CD34+alpha-SMA-SPARC- vs. carcinoma: CD34-alpha-SMA+SPARC+) as a tool in distinguishing benign from malignant breast lesion one has to keep in mind that the phenotype of granulation tissue in areas of antecedent biopsy resembles that of tumor stroma.

Connective tissue growth factor (CTGF) has recently been recognized as an important profibrotic factor and is up-regulated in various renal diseases with fibrosis. The present study describes the sequential localization of CTGF mRNA and its association with transforming growth factor (TGF)-beta1 in human crescentic glomerulonephritis (CRGN). Furthermore, we examined the phenotype of CTGF-expressing cells using serial section analysis. Kidney biopsy specimens from 18 CRGN patients were examined using in situ hybridization and immunohistochemistry. CTGF mRNA was expressed in the podocytes and parietal epithelial cells (PECs) in unaffected glomeruli. In addition, it was strongly expressed in the cellular and fibrocellular crescents, particularly in pseudotubule structures. Serial sections revealed that the majority of CTGF mRNA-positive cells in the crescents co-expressed the epithelial marker cytokeratin, but not a marker for macrophages. Moreover, TGF-beta1, its receptor TGF-beta receptor-I, and extracellular matrix molecules (collagen type I and fibronectin) were co-localized with CTGF mRNA-positive crescents. Our results suggest that CTGF is involved in extracellular matrix production in PECs and that it is one of the mediators promoting the scarring process in glomerular crescents.

It has been shown that transforming growth factor-beta (TGF-beta) has a potent stimulatory effect on the growth of chondrosarcoma cells in vitro. In order to examine the production of this family of growth factors and their receptors in vivo, we studied the expression of TGF-beta isoforms 1, 2, and 3 and of TGF-beta receptor types I and II (TGF-betaRI and TGF-betaRII) in a series of 24 chondrosarcomas of bone using immunohistochemistry and reverse-transcription polymerase chain reaction analysis. For comparison, five enchondromas and five osteochondromas were also analyzed. TGF-beta1 was expressed in 3 benign lesions (30%) and 18 chondrosarcomas (75%), with a significantly higher expression in grade-2 and -3 tumors than in grade-1 tumors ( P=0.002). TGF-beta2 was identified in 8 benign lesions (89%) and 21 chondrosarcomas (87.5%), with increased expression in grade-2 and -3 chondrosarcomas in comparison with grade-1 tumors ( P=0.05). TGF-beta3 was detected in 6 benign lesions (60%) and 17 chondrosarcomas (70.8%), with no significant differences between chondrosarcomas of different histologic grade ( P=0.6). Twenty-three chondrosarcomas (95.8%) expressed both TGF-beta receptor types I and II. Reverse-transcription polymerase chain reaction analysis performed on ten chondrosarcomas confirmed the presence of low or absent levels of TGF-beta1 and -beta2 mRNA in grade-1 chondrosarcomas, while grade-2 chondrosarcomas presented high levels of transcript of both cytokines. High levels of TGF-betaRI and RII mRNA were also detected. Chondrosarcomas with TGF-beta1 and TGF-beta2 overexpression (>20% of tumor cells) had a significantly higher expression of the cell proliferation marker MIB-1 ( P=0.006 and P=0.0003, respectively), while no significant correlation was found between TGF-beta3 expression and proliferative activity ( P=0.5). When TGF-beta isoform and receptor expression were examined with respect to disease-free survival, TGF-beta1 overexpression was significantly associated with a shorter disease-free survival ( P=0.004, log-rank test). Our data indicate that TGF-beta isoforms are produced by neoplastic cells of chondrosarcomas and could have a potential role as autocrine growth stimulators in these neoplasms.

We analyzed immunohistochemically the tissue distribution of the three major transforming growth factors-beta isoforms (TGF-beta1, -2, -3) and their receptors (TBR-I, -II and -III) in tissue samples from 38 patients with laryngeal squamous cell carcinomas. Besides a qualitative evaluation, the number of the respectively labeled cells was determined by morphometric analysis. In all tumor samples a significant staining of most tumor cells was seen both for the TGF-beta isoforms and the TBRs. Similarly, the majority of stromal cells were labeled. On semiserial sections, there were only minor differences in the distribution pattern and in the number of labeled cells between the three TGF-beta isoforms and the TBRs, suggesting that most tumor cells are actively involved in the neosynthesis of TGF-betas and TBRs; accordingly, at least most tumor cells seem to be capable of producing more than one TGF-beta form and in parallel several TBRs. With decreasing tumor cell differentiation the number of TGF-beta- and TBR-positive tumor cells decreased slightly (but not to a statistically significant degree). Interestingly, the stromal cells were labeled for TGF-betas and TBRs to a lower extent than the epithelial cells, and there was no significant difference between non-tumor-associated control stroma and the immediate peritumoral stroma. Our observations suggest an even, enhanced level of TGF-beta production in laryngeal squamous cell carcinomas, which may explain some well-known side-effects of tumor growth, such as stromal desmoplasia. In addition, the presence of immunoreactive TBR-proteins in the vast majority of tumor cells excludes the mere absence of TBRs in those carcinomas as the cause for inappropriate TGF-beta function in the tumor cells. This in turn suggests that molecular alterations either of the TBR-proteins non-affecting the synthesis and turnover or downstream alterations of the TGF-beta signaling pathway may be main reasons for the loss of response of the tumor cells to the enhanced amounts of TGF-betas.