Positive Stromal Cells Research Articles

Cytokeratin-positive subserosal myofibroblasts in gastroduodenal ulcer; another type of myofibroblasts.

To investigate the distribution and origin of alpha-smooth muscle actin (ASMA)-positive stromal cells in the perforation of human gastroduodenal ulcers. Perforative lesions of 24 surgically resected gastroduodenal ulcers were examined immunohistochemically for ASMA, HCD, CD34, CD31, CAM5.2 and HMW-CK, and double staining of ASMA and CAM5.2 was also performed. In addition, to determine the cell source of collagen, in situ hybridization of collagen I mRNA was performed. In the normal gastroduodenal wall, the reticular network of CD34-positive stromal cells was identified in the muscularis mucosa, submucosa, muscular propria, and subserosa. In the subepithelial area, many myofibroblasts were observed, whereas no CD34-positive stromal cells were seen. In areas neighboring ulcerative lesions, no CD34-positive stromal cells were observed, but a significant number of myofibroblasts were present there. In the deep layer of ulceration, numerous fusiform or stellate stromal cells strongly positive for ASMA and CAM5.2 were observed in the subserosal area around the perforation. In the same site, many cells co-expressing ASMA and CAM5.2 were identified by double staining. In contrast, in the surface layer of ulceration, stromal cells expressing only ASMA were observed. The cytokeratin-positive subserosal myofibroblastic cell in human gastroduodenal ulcer is a novel type of myofibroblast.

The endometria of patients with endometriosis show higher expression of class I human leukocyte antigen than the endometria of healthy women

To compare the expression of class I human leukocyte antigen (HLA I) in endometrial samples from patients with and without endometriosis. Cross-sectional study. Acute-care teaching hospital in Barcelona, Spain. The endometriosis group included 32 patients for whom the only diagnosis during an operation was endometriosis. The control group included 20 women who underwent a laparoscopy and in whom no evidence of endometriosis or any other genital disease was seen. Samples of endometrium were obtained by curettage and immediately frozen. A pan-HLA I mouse antihuman IgG2a monoclonal antibody was used for immunohistochemical study. Frequency of positive glandular and stromal cells was evaluated in each section. A significantly higher expression of HLA I in the endometriosis group than in controls, both in the glandular cells (median 100% vs. 80%) and in the stromal cells (median 60% vs. 20%), was observed. Patients with endometriosis had a significantly higher expression of HLA I molecules in endometrial cells than did the controls. This could be a possible explanation for their higher resistance to natural killer cytolysis.

Androgen receptor levels are increased by interferons in human prostate stromal and epithelial cells

Proliferation of normal and malignant prostate epithelium is regulated by androgen stimulation via both the androgen receptor (AR)-positive stromal and epithelial cells. However, it is not known how AR expression is regulated in human prostate cells. We report that treatment of normal human prostate stromal cells (PrSCs) with type I IFN (alpha or beta), but not type II IFN (gamma), resulted in increased levels of AR protein. The maximal increase in AR protein levels was dependent on the dose and the duration of the IFN-alpha treatment. We found that the increase in AR protein levels was independent of de novo transcription and protein synthesis. Interestingly, the IFN-alpha treatment of PrSCs resulted in considerable nuclear accumulation of AR, stimulation of AR-mediated transcription of reporter genes, and retardation of cell proliferation. Furthermore, treatment of normal human prostate epithelial cells with IFNs (alpha, beta or gamma) also resulted in increased levels of AR protein. Together, our observations identify the androgen receptor as an IFN-regulated protein in normal human prostate stromal and epithelial cells and predict that IFN-induced levels of AR in prostate cells contribute to the regulation of androgen signaling.

Cellular and stromal characteristics in the scirrhous hepatocellular carcinoma: Comparison with hepatocellular carcinomas and intrahepatic cholangiocarcinomas

Scirrhous hepatocellular carcinoma (SHCC) is a rare variation of HCC, for which characteristics of tumor cells and the fibrotic stroma have not been clarified in detail. The present study was therefore carried out to elucidate cytological features of tumor and stromal cells and components of the stromal extracellular matrix in 15 SHCC patients undergoing hepatectomy without preoperative transarterial embolization. Diagnosis was on the basis of a scirrhous histological pattern exceeding 50% of the tumor area. Expression of cytoplasmic and extracellular matrix proteins was compared among SHCC, HCC and intrahepatic cholangiocarcinoma (ICC) cases with immunohistochemical staining. The lesions could be histologically divided into radiating and sinusoidal types. Common stromal components of SHCC and ICC were collagen types I and III. There was no expression of laminin-5 in the stroma of SHCC, but it was present in almost all ICC cases. Tenascin-C expression was significantly lower in the SHCC cases and its distribution differed between SHCC and ICC. Matrix metalloproteinase-7 (MMP-7) expression was significantly higher in SHCC compared with HCC. Almost all stromal cells were alpha-smooth muscle actin-positive both in SHCC and ICC, whereas glial fibrillary acid protein (GFAP)-positive stromal cells were significantly more increased in ICC than in SHCC. SHCC clearly differed from HCC with respect to collagen types I, III and MMP-7 expression, and from ICC with regard to stromal components including laminin-5, tenascin-C and GFAP(+) stromal cells.

IMMUNOLOCALIZATION OF ANDROGEN RECEPTOR AND ESTROGEN RECEPTORS α AND β IN HUMAN FETAL TESTIS AND EPIDIDYMIS

Expression and cellular localization of the androgen receptor (AR) and estrogen receptor (ER) isoforms were determined using antibodies specific to these receptors and to specific cell types. Gonads and genitourinary structures were removed from 5 human male fetuses 7 to 22 weeks of gestational age. Sections were stained with antibodies to AR, ERalpha and ERbeta, P450 scc and smooth muscle actin. AR was present in undifferentiated gonadal cells, peritubular myoid cells and in some Leydig and stromal cells at 7 weeks of gestation. The number of AR positive peritubular myoid cells remained constant through 22 weeks of gestation but the number of AR positive stromal cells continued to increase through 22 weeks. ERalpha was apparent by 12 weeks of gestation with perinuclear staining of Leydig cells, peaked at 16 weeks and then diminished. ERbeta was first observed at 7 weeks in undifferentiated gonadal cells. By 12 weeks of gestation ERbeta was apparent in germ cells, PTMC and Leydig cells. In the epididymis AR was expressed in the epithelium and stroma of the efferent ductules and the ductus epididymis by 7 weeks of gestation with increased expression by 12 weeks. A similar pattern of staining was observed for ERbeta. By contrast, staining of ERalpha was observed only in the epithelium of the epididymis from 7 weeks of gestation onward with no apparent ERalpha staining in the tail of the epididymis. These findings are compatible with the well-known roles of androgen signaling in sexual differentiation and spermatogenesis in humans. The role of estrogens in the developing human testis and epididymis remains unknown.

Myofibroblasts in stroma of odontogenic cysts and tumors can contribute to variations in the biological behavior of lesions

Stromal myofibroblasts (MF) have the potential to facilitate progression of neoplastic epithelial lesions that could contribute to their biological behavior. To assess immunohistochemically the frequency of stromal MF in different odontogenic cysts and tumors and correlate it to their aggressive biological behavior. The study included cases of dentigerous cyst (DC, n = 7), odontogenic keratocyst-parakeratinized type (OKC-P, n = 8), orthokeratinized type (OKC-O, n = 9), ameloblastic fibroma/fibro-odontoma (AMF/O, n = 11), unicystic ameloblastoma (UAM, n = 6), and solid ameloblastoma (SAM, n = 7). Cases of oral squamous cell carcinoma (SCC, n = 5) served as control. Myofibroblast frequency was assessed as the number of alpha smooth muscle actin (alphaSMA)-positive stromal cells in 10 high-power fields, presented as the mean number of positive cells per field. Counts showed that mean number of positive cells in OKC-P (25.7+/-11.4) was significantly higher than in DC (8.7+/-11.6) (p = 0.024) and in SAM (29+/-7) it was significantly higher than in UAM (14.9+/-4.9) and AMF/O (5.6+/-7.5) (p < 0.001). Counts in OKC-P and SAM were not significantly different from SCC (21.3+/-5.3) (p > 0.05). The high frequency of stromal MF in known aggressive odontogenic lesions, such as OKC-P and SAM, implies that MF can contribute to the biological behavior of these odontogenic lesions. Various pharmacological agents that control stromal MF can be used as an aid to reduce extensive and mutilating surgery in cases of remarkably aggressive odontogenic lesions.

Influence of β1 Integrin Intracytoplasmic Domains in the Regulation of VLA-4-Mediated Adhesion of Human T Cells to VCAM-1 under Flow Conditions

The VLA-4 integrin supports static cell-cell, cell-matrix adhesion, and dynamic interactions with VCAM-1. Although functions for well-conserved beta(1) integrin cytoplasmic domains in regulating static cell adhesion has been established, the molecular basis for beta(1) integrin-dependent arrest on VCAM-1 under flow conditions remains poorly understood. We have transfected the beta(1) integrin-deficient A1 Jurkat T cell line with beta(1) cDNA constructs with deletions of the NPXY motifs and specific mutations of tyrosine residues. Deletion of either NPXY motif impaired static adhesion induced by CD2 or CD47 triggering or direct beta(1) integrin stimulation. In contrast, PMA-induced adhesion to VCAM-1 was unaffected by deletion of the NPIY motif and only slightly impaired by deletion of NPKY. Moreover, deletion of the NPIY motif resulted in enhanced rolling and reduced arrest on VCAM-1 under shear flow conditions. In contrast, deletion of the NPKY motif did not alter arrest under flow. Although tyrosine to phenylalanine substitutions within two NPXY motifs did not alter static adhesion to VCAM-1, these mutations enhanced arrest on VCAM-1 under flow conditions. Furthermore, although deletion of the C'-terminal 5 AA of the beta(1) cytoplasmic domain dramatically impaired activation-dependent static adhesion, it did not impair arrest on VCAM-1 under flow conditions. Thus, our results demonstrate distinct structural requirements for VLA-4 function under static and shear flow conditions. This may be relevant for VLA-4 activity regulation in different anatomic compartments, such as when circulating cells arrest on inflamed endothelium under shear flow and when resident cells in bone marrow interact with VCAM-1- positive stromal cells.

506. Transductional and Genome Biodistribution of Novel AAV Serotype Vectors after Systemic Delivery and Their Liver Specific Dose Response Profiles in Mice

Recent discovery of a novel family of primate AAVs led to the developement of vectors with unprecedented efficiency in liver. To search for other potential applications of these vectors, we treated C57BL/6 mice intravenously with either 1|[times]|1011 or 1|[times]|1012 GC/mouse of AAVs 2, 5, 7, 8 and 9CBnLacZ. At days 3, 30 and 90, 13 tissues from treated animals were analyzed for LacZ expression by X-gal histochemical staining and vector genome quantification by TaqMan PCR. Analysis of day 3 samples revealed that AAVs 7, 8 and 9 derived vectors displayed more robust and broader tissue transduction profiles. Liver, cardiac and diaphragm muscles were the primary transduction targets by the 3 vectors. At the dose of 1|[times]|1011, more than 90% of hepatocyes were transduced by AAVs 8 and 9, 60-70% by AAV7. However, at a 10-fold higher dose, 100% of hepatocytes in all 3 vector groups stained blue. In the low dose groups, AAV9 transduced cardiac myocytes the best, followed by AAV8 and AAV7. But all 3 vectors achieved remarkable transduction in the heart at the high dose. All 3 novel vectors resulted in significant numbers of X-gal positive myocyte nuclei in the diaphragm muscle, particularly at the high dose. Hepatocyte transduction achieved by AAV 2 and AAV5 were only a few percent at the low dose but a clear dose response was observed in AAV2 high dose animals. No transduction events were detected in heart and diaphragm sections of the AAVs 2 and 5 treated animals. In addition, X-gal stained muscularis cells and smooth muscle cells of some tissues in GI track including stomach, small bowel and colon were readily noticeable in AAVs 7, 8 and 9 but not in the AAV2 and 5 groups. X-gal positive stromal cells but not follicles in the ovary were occasionally visible in all vector and dose groups. Several cell types including renal tubular cells in kidney were sporadically found to be transduced by AAVs 7, 8 and 9. These 3 vectors also transduced some acinar cells, interlobular connective tissues but rarely islets in pancreas. With all vector and dose groups, no transduction events were recognized in the brain, anterior tibialis muscle and lung tissues. In contrast to distinguished tissue transductional profiles of AAV serotype vectors, there was no serotype specific genome targeting observed. In most of tissues analyzed, genome copies of all rAAVs in a particular tissue are quite similar, suggesting that the capsid directed genome processing pathway represent the determining factor for the serotype specific vector biology.

Reduced Intensity Conditioning Compared to Standard Conditioning Preserves the In Vitro Growth Capacity of Bone Marrow Stroma, Which Remains of Host Origin

The ability of bone marrow (BM) samples to generate confluent stromal layers in long-term BM cultures (LTBMC) was used as a surrogate assay to determine the in vivo toxic effects of different conditionings on stromal cells. Here, 32 patients receiving a fludarabine-based reduced intensity conditioning regimen (FBM) were compared to those in a control group of 23 patients treated with standard busulfan/cyclophosphamide (BuCy; 14 patients) or TBI-based (TBI 12 Gy/VP16/cyclophosphamide; 9 patients) conditioning. BM was aspirated before conditioning, and at day +30 and/or at day +100, obtaining positive stromal cell growth in vitro in 58%, 47%, and 65%, respectively. FBM conditioning did not alter the ability of BM to generate stromal layers both early (day +30, 75%+) or late (day +100, 80%+) after hematopoietic cell transplantation (HCT) as compared to pre-HCT (66.6%+). FBM-treated patients formed confluent stroma significantly more often than standard-treated patients (85% vs. 38% patients; p < 0.05). In an univariate analysis, standard conditioning remained the only factor predicting stromal growth impairment after allogeneic HCT. The ex vivo-generated stromal layers from 5 female, FBM treated, sex-mismatched, and peripheral blood stem cell (PBSC) transplanted patients were analyzed by combined FISH-Y and immunofluorescence stains (Vimentin, CD14, CD45) and found to be exclusively of recipient origin. We conclude that FBM reduced intensity conditioning results in reduced, if any, stromal damage as compared to standard myeloablative treatment. The novel, donor-derived, hematopoiesis in FBM patients after allogeneic transplantation is supported and maintained by a host-derived BM stromal microenvironment.

.ALPHA.-Smooth Muscle Actin-positive Stromal Cells Reactive to Estrogens Surround Endometrial Glands in Rats but not Mice

In human endometrium, α-smooth muscle actin (α-SMA)-positive stromal cells (SMA-SCs) surround endometrial glands, and the α-SMA expression is regulated by estrogen. The biological significance of these cells remains to be elucidated, and no information is available with regard to their animal counterparts. The present study, therefore, investigated SMA-SCs in the uteri of female Donryu rats and CD-1 mice. SMA-SCs with morphological similarities to those in the human were detected around the endometrial glands in normal cycling rats, but not in mice. Furthermore, the rat SMA-SCs disappeared after ovariectomy but returned with estrogen replacement in a duration- dependent manner, suggesting the regulatory role of estrogens similar to the human situation. Thus, SMA-SCs are present in rats, but not in mice, with characteristics close to their human counterparts. Their biological significance now needs to be elucidated by comparative studies. (J Toxicol Pathol 2005; 18: 47-52)

Expression of CD10 in Basal Cell Carcinoma

We investigated the expression of CD10 by an immunohistochemical method in 51 basal cell carcinomas (BCCs), eight pilomatricomas, five trichoblastomas, two trichofolliculomas, three sebaceomas, five sebaceous carcinomas, ten syringomas, two spiradenomas, ten poromas, four porocarcinomas, one eccrine duct carcinoma (not otherwise specified, NOS), six mixed tumors of apocrine origin, and nine squamous cell carcinomas (SCCs). We detected strong expression of CD10 in tumor cells of BCC (86%), and found that the smaller the number of positive tumor cells, the larger the number of positive stromal cells, in particular in sclerosing BCCs. Spearman's rank correlation test revealed a significant negative correlation in BCCs between the expression of CD10 in tumor cells and that in stromal cells (P = 0.001). In all pilomatricomas (100%) and in four trichoblastomas (80%), strong expression was also detected in tumor cells. There was no detectable expression in trichofolliculomas. One sebaceoma (33%) and two sebaceous carcinomas (40%) expressed CD10 in a similar fashion to BCCs. All tumors of eccrine gland origin, including syringoma, spiradenoma, poroma, porocarcinoma, and eccrine duct carcinoma (NOS), did not express CD10. Five mixed tumors (83%) were immunopositive. In SCC, CD10 was overexpressed only in the stromal cells. These findings support the hypothesis that BCC is derived from the folliculo-sebaceous apocrine unit, especially having the same origin as trichoblastoma and pilomatricoma. CD10 might be an indicator of tumor invasiveness if it is expressed in stromal cells, while it might be a marker of follicular differentiation if it is expressed in the actual tumor cells of cutaneous epithelial neoplasms.

The disappearance of CD34-positive and alpha-smooth muscle actin-positive stromal cells associated with human intra-uterine and tubal pregnancies.

In order to elucidate the change in alpha-smooth muscle actin (ASMA)-positive and CD34-positive stromal cells associated with pregnancy, we examined endometrial and Fallopian tube tissues from 40 patients including normal endometrium (n=10), intra-uterine pregnancy (n=10), normal Fallopian tube (n=10), and tubal pregnancy (n=10), using immunohistochemistry. In normal endometrium, only a few ASMA-positive cells were focally observed. Additionally, a wide range of CD34-positive stromal cell abundance was observed. In normal Fallopian tube mucosa, a small to moderate number of both ASMA-positive and CD34-positive stromal cells was observed. Neither ASMA-positive nor CD34-positive stromal cells were observed anywhere in the decidual stroma during both intra-uterine and tubal pregnancies. Likewise, a varying abundance of ASMA-positive cells but no CD34-positive stromal cells were observed at the fetal side during both intra-uterine and tubal pregnancies. In conclusion, the disappearance of CD34-positive and ASMA-positive stromal cells may be an indicator of decidualisation induced change in the stroma during both intra-uterine and tubal pregnancies. ASMA-positive stromal cells at the fetal side associated with pregnancy may play a role in the production of villous extracellular matrix or regulation of blood flow.

Induction of bone marrow stromal cells to neurons: differentiation, transdifferentiation, or artifact?

Differentiation of stem cells toward a neuronal lineage normally involves a gradually progressive restriction in developmental potential and is regulated by a diverse set of specific and temporally precise genetic events. However, recent studies have indicated that both rodent and human bone marrow stromal cells (MSCs) can be rapidly (within minutes to hours) induced to differentiate into neurons in vitro by relatively simple chemical means (using beta-mercaptoethanol [BME] or dimethylsulfoxide [DMSO] and butylated hydroxyanisol [BHA]; Woodbury et al. [ 2000] J. Neurosci. Res. 61:364-370). The ability to transdifferentiate an easily accessible cell source into neurons could have substantial potential for promoting neural repair. We therefore explored the potential of simple chemical methods to transdifferentiate other cell types, including primary rat fibroblasts, primary human keratinocytes, HEK293 cells, rat PC-12 cells, and as positive control rat bone marrow stromal (BMS) cells. Surprisingly, all cells except for keratinocytes adopted at least partial "neuron-like" pyramidal cell morphology with fine-cellular extensions resembling neurites upon stimulation with BME or DMSO/BHA. However, time-lapse microscopy indicated that the chemical exposure of MSCs did not result in new neurite growth but rather cellular shrinkage, with retraction of the majority of existing cell extensions, leaving only few, fine neurite-like processes. To determine whether the chemically induced transdifferentiation resulted from simple cellular toxicity, MSCs were exposed to various stressors, including detergents, high-molarity sodium chloride, and extremes of pH. In all cases, cellular shrinkage and adoption of pseudoneuronal morphology were observed. Concomitantly with cellular shrinkage, apparent increases in immunolabeling for the neuronal markers NSE and NeuN were detected in the cell soma that could not be confirmed by RT-PCR. Furthermore, blockade of protein synthesis with cycloheximide did not prevent cells from adopting "neuron-like" morphology after chemical induction. Thus, morphological changes and increases in immunolabeling for certain cellular markers upon "chemical induction" of MSCs are likely the result of cellular toxicity, cell shrinkage, and changes in the cytoskeleton and do not represent regulated steps in a complicated cellular differentiation process.

Expression of cyclooxygenase-2 in canine epithelial nasal tumors.

Cyclooxygenase-2 (COX-2) is an enzyme upregulated in some human and animal tumors. Enzymatic products are associated with tumorigenic activities. Given the poor response of canine nasal tumors to radiation, we considered the possibility that some of this resistance may be associated with COX-2 expression. To test this, 21 formalin-fixed, paraffin-embedded, and archived biopsy samples from canine epithelial nasal tumors were analyzed for COX-2 expression using immunohistochemistry. The biopsies were collected from dogs prior to radiation therapy. COX-2 expression was present in 17 of 21 (81%) tumors. The expression was observed in several different tumor types, including nasal carcinomas, adenocarcinomas, and squamous cell carcinomas. Samples from five control dogs without nasal neoplasia were also analyzed for COX-2 staining. These specimens were characterized by varying degrees of lymphoplasmacytic rhinitis with scattered regions of COX-2 positive respiratory epithelial and stromal cells. Whether the intensity and distribution of COX-2 expression in nasal tumors can be used as a prognostic marker requires further investigation. A combination therapy of irradiation and a selective COX-2 inhibitor appears worthy of clinical investigation in the treatment of canine epithelial nasal tumors.

Coexpression of Keratinocyte Growth Factor and Its Receptor in Normal and Prostate Cancer Tissues: Possible Formation of Autonomous Andromedin Loop

Keratinocyte growth factor (KGF), an androgen-dependent epithelial mitogen, and its receptor (KGFR) have been implicated in the regulation of cell growth and differentiation in prostate tissue. This study was designed to determine the expression and role of KGF and KGFR in normal and prostate cancer tissues, especially in relation to cell kinetics. In 41 cases of prostate cancer in paraffin-embedded specimens, the expression of KGF and KGFR at the levels of protein and mRNA was analyzed by immunohistochemistry using newly raised antibodies and in situ hybridization, respectively. We also examined expression of androgen receptor (AR) and Ki-67 labeling index (LI). In normal and hyperplastic prostate tissues, both KGF mRNA and protein were localized in AR positive stromal cells, while those of KGFR were localized in glandular epithelial cells. In prostate cancer, however, coexpression of KGF and KGFR was observed in 14/41 cases, and significantly correlated with high Gleason scores, bone metastasis and high Ki-67 LI. The relapse-free survival of patients suffering from prostate cancers coexpressing KGF and KGFR was significantly shorter than that of patients from the other ones. Therefore, our results indicate that coexpression of KGF and KGFR in prostate cancer may predict metastatic and proliferative activities, possibly due to the formation of an autonomous andromedin loop.

A comparison of EUS features between CD-117 positive GI stromal tumors and CD-117 negative GI spindle cell tumors

GI stromal tumors are spindle cell tumors that stain positive for immunohistochemical CD-117 (c-kit). Prognostic factors for malignancy include size (> or =4 cm), mitotic index (5 mitotic figures/50 high-powered fields), and ulcerated, cystic, or necrotic areas within the tumor. The purpose of this study was to compare these features in c-kit positive vs. c-kit negative tumors. All patients referred for EUS of submucosal lesions were identified, and histopathology, including immunohistochemical staining, was reviewed to determine all diagnoses of GI stromal tumors. Size, echo pattern, and presence of cystic spaces and ulceration were recorded as diagnosed by EUS. Histopathologic diagnoses were made by FNA or endoscopic submucosal-mucosal resection. If surgical resection followed, the surgical diagnosis, staining pattern, mitotic index, and presence of ulceration, necrosis, and nuclear atypia were recorded. Forty patients (21 men, 19 women; 38 white, 2 African American; mean age 58 +/- 2.6 years) had 46 EUS procedures performed for evaluation of spindle cell tumors. Seventeen stained positive for c-kit (mean age, 59 +/- 3.6 years; range 19 to 80 years) and 12 negative (mean age, 57 +/- 3.8 years; range 31 to 76 years); 11 were not stained for c-kit (excluded from analysis). On EUS, 7 were ulcerated, 3 cystic, and 6 were larger than 4 cm. This group of findings was observed in 12 patients, 11 of whom had c-kit positive tumors (11/17 vs. 1/12; p = 0.006). Tumors positive for c-kit were larger (42.4 +/- 5.5 mm vs. 19.0 +/- 5.9 mm; p = 0.005). There were 13 c-kit positive tumors in the stomach, 2 in the duodenum, and 1 each in the esophagus and at the gastroesophageal junction. Of the 12 c-kit negative tumors, 8 were located in the esophagus and 1 at the gastroesophageal junction (9/12 vs. 2/17; p < 0.01). Surgical resection was performed on 13 patients, 12 of whom had c-kit positive tumors, and 3 of these 12 tumors had greater than 5 mitoses per 50 high-powered field. If a GI stromal tumor is suspected, EUS-FNA with immunohistochemical staining should be performed for CD-117 (c-kit). C-kit tumors are more likely to have malignant features and should be resected or subjected to close clinical follow-up.

Ets1 as a marker of malignant potential in gastric carcinoma.

Ets1 proto-oncogene is a transcription factor involved in the activation of several genes of tumor invasion and metastasis. We aimed to determine the relationship between the extent and intensity of Ets1 expression and patients' clinicopathological factors in gastric carcinoma. Immunohistochemical analysis was performed for gastric tumor paraffin-embedded sections, followed by image analysis. Ets1 was not expressed in the normal gastric epithelium and its surrounding cells. The percentage of Ets1 expressing cells detected increased significantly in both epithelial tumor and stromal cells from high T classification, lymph node metastasis positive, clinical advanced-stage groups (P<0.001). The level of Ets1 staining in epithelial tumor cells also reflected the degree of cell differentiation. The percentage of epithelial and stromal cells expressing Ets1 was significantly correlated with the presence of lymph node metastasis (P=0.014 and P<0.001 respectively). Ets1 expression was not observed in tissue samples from patients with benign gastric ulcers. Ets1 protein expression in epithelial tumor cells reflects the degree of differentiation, and the percentage of Ets1 positive tumor and stromal cells correlates with lymph node metastasis. Thus Ets1 is a valuable marker of malignant potential in terms of invasiveness and metastasis of gastric carcinoma. It is also possible that inhibition of Ets1 is a potential avenue for therapy in gastric cancer.

High molecular weight caldesmon positive stromal cells in the capsule of thyroid follicular tumours and tumour-like lesions

Aims: To investigate the smooth muscle nature of the spindle stromal cells in the capsule of thyroid tumours and tumour-like lesions. Methods: Immunostaining for high molecular weight caldesmon (HCD), a...

α Smooth muscle actin positive stromal cells in gastric carcinoma

Aims: To investigate the distribution and roles of α smooth muscle actin (ASMA) positive stromal cells (ASMA+ cells), which belong to the myofibroblast group, within gastric carcinomas, with reference to...

Lack of CD34 positive stromal cells within angiomyomas (vascular leiomyomas).

To investigate the role of CD34 positive stromal cells in the morphogenesis and tumour growth regulation of angiomyomas (vascular leiomyomas). Histochemical analysis using monoclonal antibodies to CD34 and CD31 was performed in 10 angiomyomas and their adjacent soft tissue. CD34 positive stromal cells were not seen within the tumour tissue; the thick walled vessels within the tumours lacked CD34 positive stromal cells. In contrast, bundles of CD34 positive stromal cells were detected at the tumour border of all of the angiomyomas and in the adventitial tissue of the surrounding normal vessels. The lack of CD34 positive stromal cells within an angiomyoma is associated with the characteristic morphology of an angiomyoma.