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Cytopathology 02/2010; 21(1):52-5. · 1.59 Impact Factor
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ABSTRACT: An invasion-independent pathway has been proposed as a novel mechanism in blood-borne metastasis, where tumour cells enveloped by sinusoidal tumour vessels enter the circulation without vascular invasion. We previously identified the secretory leukocyte protease inhibitor (SLPI) as a candidate gene responsible for this pathway. In this study, the functional role of SLPI in metastatic dissemination was investigated. We transfected the SLPI gene into a poorly metastatic clone of the MCH66 mouse mammary tumour cell line. Over-expression of SLPI promoted in vivo growth and spontaneous metastasis to the lung, whereas it suppressed invasive activity in vitro. The inoculated tumours of SLPI-transfectants exclusively induced a sinusoidal vasculature and subsequently produced endothelial-coated tumour emboli, which are morphological indices of the invasion-independent pathway. In addition, exogenous SLPI inhibited the migration activity through Matrigel of both tumour cells and human umbilical vein endothelial cells (HUVECs). In vivo angiogenesis assays also demonstrated that SLPI suppressed the migration of newly formed blood vessels. These results suggest that an anti-migratory effect of SLPI on tumour-associated endothelial cells may induce vascular remodelling to form a sinusoidal architecture, and consequently promote invasion-independent metastasis. This study provides a new model for metastasis, based on the mechanism regulated by anti-invasive factors, such as SLPI.
The Journal of Pathology 07/2007; 212(2):152-60. · 6.32 Impact Factor
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ABSTRACT: To differentiate uterine leiomyoma (LM) with 'pseudosarcomatous' features from leiomyosarcoma (LMS). We hypothesized that because pseudosarcomatous LM is only a benign variant of conventional LM, it may have some characteristics different from LMS.
Fourteen uterine smooth muscle tumours, which had been diagnosed as LMS previously, were reviewed and divided into adverse outcome (true LMS; seven cases) and excellent outcome groups (presumed pseudosarcomatous LM; seven cases) based on their clinical course. The tumours of the adverse outcome group were composed of rather uniform long spindle cells similar to those of leiomyosarcoma arising from the soft tissue. All tumours in this group had coagulative necrosis and all but one case were diagnosed preoperatively as malignant. In contrast, the tumours of the excellent outcome group showed significant histological diversity both between tumours and also in the same tumour and areas indistinguishable from conventional LM were often seen. All the tumours of this group were diagnosed preoperatively as benign. Immunohistochemically, all tumours of the excellent outcome group expressed progesterone receptor, often intensely, and also frequently expressed oestrogen receptor. In contrast, all the tumours of the adverse outcome group lacked them completely.
Pseudosarcomatous LM has characteristics useful for differentiating it from LMS, which are common in conventional LM.
Histopathology 05/2006; 48(5):563-8. · 3.08 Impact Factor
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ABSTRACT: We present three distinctive uterine tumours which exhibited immature smooth muscle differentiation mimicking smooth muscle cells of the fetal uterus.
The patients were 45, 46 and 49 years old, and all of them had simple hysterectomies. Grossly, all tumours were present in the uterine body, and two of the three tumours were well demarcated 60-mm and 85-mm lesions, and the other tumour was a small 25-mm incidental lesion within multiple conventional leiomyomas. The tumours had varied histological features and were composed of round epithelioid, rhabdoid and large vacuolated cells intermingled with spindle-shaped cells to various degrees. Although their round vesicular nuclei showed mild to moderate variation in size, prominent nuclear atypia was not seen. Necrosis and mitotic figures suggesting biological aggressiveness were not present in any of the tumours. Immunohistochemically, tumour cells were intensely positive for desmin and alpha-smooth muscle actin, whereas positivity for heavy molecular weight caldesmon was restricted. In addition, two cases were positive for non-muscle myosin heavy chain (SMemb). Ultrastructurally, most tumour cells contained various amounts of intermediate filaments which were occasionally abundant and aggregated as in rhabdoid cells. Well-developed myofilaments with focal densities were observed in only a few tumour cells. Intermediate filaments and bundles of thin filaments without dense bodies were often intermingled and they occasionally formed distinctive complexes with many irregular dense body-like structures and crystalloid bodies. Other cytoplasmic organelles including rather rich mitochondria, some rough endoplasmic reticulum and free ribosomes were also common.
These findings support their immature smooth muscle cell differentiation which mimics the mesenchymal cells of fetal uterus during 14-26 weeks of gestation. The term 'uterine leiomyoblastoma' is thought to be appropriate for describing these distinctive immature smooth muscle tumours.
Histopathology 05/2003; 42(4):379-86. · 3.08 Impact Factor
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ABSTRACT: Extra-abdominal desmoid fibromatosis is an uncommon tumour. We present here two exceptional familial cases of extra-abdominal desmoid fibromatosis, one of which was synchronous and metachronous.
The first patient was a 37-year-old woman who had noted a tumour growing on the dorsum of her right foot when she was 12 years old. She underwent excision of the tumour but in the following year the tumour recurred locally and grew into multiple nodules. Subsequently, multicentric tumours appeared in her knee, distal and posterior aspects of her thigh, right back and right anterior shoulder. Polyostotic fibrous dysplasia of the femur and cranium was found on radiological examination. The second patient was a 74-year-old man, the uncle of the first patient. He underwent an excisional operation of a tumour on the internal malleolus surface of his fibula when he was 46 years old. The tumour recurred 7 years later and was excised. His post-operative course has been uneventful. The histology of the primary and recurrent tumours was distinctive and consistently showed hyalinizing scar-like features.
Familial cases of extra-abdominal desmoid fibromatosis with extensive multicentric lesions and distinctive hyalinizing scar-like features are described. Recently, attenuated familial adenomatous polyposis with familial desmoid fibromatosis has been recognized, and familial desmoid fibromatosis without adenomatous polyposis may also be one of its variants. Although the present cases have no history of colon polyposis or carcinoma, monitoring of the intestinal tract would seem to be indicated.
Histopathology 09/2002; 41(2):118-21. · 3.08 Impact Factor
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ABSTRACT: To investigate the relation of fatty acid synthase (FAS) expression to the clinicopathological characteristics of gastric cancers and gastric tumorigenesis.
FAS expression was examined immunohistochemically in 626 gastric cancers, 51 gastric adenomas, and non-neoplastic epithelium contiguous with cancer tissue including normal foveolae, intestinal metaplasia, regenerative epithelium, and gastric glands. FAS expression was found in more than 70% of gastric cancers. Interestingly, it occurred preferentially in differentiated carcinomas, male cases, and in patients over 51 years old. Although previous reports showed that FAS expression is closely related to cancer progression, in gastric cancers FAS expression had no relationship with prognosis, cancer progression as indicated by depth of invasion, venous and lymphatic permeation, and distant metastasis. Gastric tubular adenoma and intestinal metaplasia, which are thought to be associated with well-differentiated gastric carcinomas, showed a frequency of FAS expression similar to that of differentiated carcinomas; however, normal foveolae and gastric glands showed no or less FAS expression.
FAS expression occurs at the early stage of tumorigenesis and plays important roles in the formation of precancerous foci rather than in the progression of carcinoma of the stomach.
Histopathology 02/2002; 40(1):71-9. · 3.08 Impact Factor
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ABSTRACT: Myofibroblastic tumors are fairly recently established soft tissue neoplasms. Although most of them appear to be benign, myofibrosarcoma of the soft tissue, seemingly their malignant counterpart, have been reported. We describe the clinicopathologic and radiologic features of four cases of myofibrosarcoma arising from the bone. All but one of the patients were women ranging in age from 60 to 71 years. Two tumors occurred in the metaphyses of distal femurs and the others arose in the iliac bones. On radiologic examination all tumors exhibited well-demarcated lytic destructive lesions without periosteal reaction. Two tumors were localized in the bone, whereas the other two extended into surrounding soft tissues. Histologically, all tumors were composed principally of a mixture of a cell-rich fascicular area and a hypocellular fibrous area. In the former area tumor cells had rather eosinophilic spindle-shaped wavy cytoplasm and were arranged in interlacing fascicles and small storiform patterns with variable numbers of inflammatory cells. Tumors occasionally showed prominent pleomorphism, and large cells with hyperchromatic nuclei were seen. In contrast, hypocellular areas had various features, including collagenous, hyalinous scar-like and rarely keloid-like areas. Focal coagulation necroses were present in all but one tumor. Immunohistochemically, the tumors were positive for vimentin, muscle actin (HHF35), alpha-smooth muscle actin, calponin, and desmin, whereas all of them were negative for high molecular weight caldesmon. On follow-up there was one fatal case with distant metastases, whereas the clinical courses of other cases after wide resection were excellent. Myofibrosarcoma of the bone has distinctive histopathologic features, which should be distinguished from those of other bone tumors with myoid differentiation.
American Journal of Surgical Pathology 01/2002; 25(12):1501-7. · 4.35 Impact Factor
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ABSTRACT: A case of ovarian fibrosarcoma producing multiple cytokines is presented. The tumor occurred in the left ovary of a Japanese woman with epigastralgia, remittent fever, leukocytosis and slight thrombocytosis with moderate increase of mast cells in bone marrow, but lack of hormonal abnormality. The resected tumor of the ovary was well encapsulated and it was composed of spindle-shaped tumor cells and scattered tubules with marked mast cell infiltration. The tumor recurred in the pelvic cavity 14 months later, accompanied by similar signs and symptoms as occurred with the primary tumor. Serum levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha were elevated. The recurrent tumor showed similar histological findings to those of the primary tumor, except for lack of tubules. Tumor cells revealed a focally positive immunoreaction for vimentin, IL-6 and TNF-alpha and alpha-inhibin. Reverse transcription-polymerase chain reaction using total RNA obtained from the recurrent tumor demonstrated mRNA expression of IL-6, IL-10, TNF-alpha and stem cell factor. This is a rare case of ovarian fibrosarcoma producing multiple cytokines, resulting in atypical clinical findings.
Pathology International 10/2001; 51(9):739-43. · 1.62 Impact Factor
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ABSTRACT: Pseudosarcomatous myofibroblastic tumors (PMTs) of the urogenital tract are rare but distinctive lesions. Despite their benign behavior, they are frequently misinterpreted as leiomyosarcomas and rhabdomyosarcomas in preoperative biopsies and even in resected specimens because of their atypical spindle-cell features. Precise diagnosis of PMTs is important to avoid unnecessary radical therapy. We analyzed urogenital myoid tumors to clarify which of their characteristics are useful for the differential diagnosis.
We evaluated 7 urogenital myoid tumors consisting of 3 PMTs, 2 leiomyosarcomas, and 2 rhabdomyosarcomas. We studied the expression of various immunohistochemical muscle-cell markers including desmin, muscle-specific actin, alpha-smooth muscle actin, high-molecular-weight caldesmon, and myogenin.
Desmin, muscle-specific actin, and alpha-smooth muscle actin were noted variably in all tumor types, whereas high-molecular-weight caldesmon was expressed only in leiomyosarcomas, and myogenin was expressed only in rhabdomyosarcomas.
High-molecular-weight caldesmon and myogenin are useful for differentiating urogenital PMTs from myosarcomas.
Archives of pathology & laboratory medicine 09/2001; 125(8):1070-3. · 2.58 Impact Factor
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ABSTRACT: Malignant cells show increased glucose uptake in vitro and in vivo, which is believed to be facilitated by glucose transporters (Gluts). Expression of Glut1, one of the Gluts, has been described in malignancies of the esophagus, colon, pancreas, lung, and brain, but to the authors' knowledge the significance of Glut1 expression in human gastric carcinoma has not been elucidated. The objective of the current study was to examine the expression and distribution of Glut1 and its relation to clinicopathologic parameters in patients with gastric carcinoma.
Immunohistochemistry with anti-Glut1 antibody was performed on 617 gastric carcinomas and 50 tubular adenomas of the stomach. Glut1-positive and Glut1-negative carcinomas were analyzed for their clinicopathologic characteristics including histologic subtype, depth of invasion, vascular permeation, lymph node and hepatic metastasis, peritoneal dissemination, and prognosis.
None of the adenomas expressed Glut1, whereas 182 of 617 carcinomas (29.5%) were positive for the protein. Signet ring cell carcinoma and mucinous adenocarcinoma rarely were positive (2.0% and 6.3%, respectively) and papillary adenocarcinoma (44%) showed slightly higher positivity for Glut1 than tubular (32%) or poorly differentiated adenocarcinoma (28%). Glut1-positive tumor cells were localized mainly in the central part of tumor nests with or without peripheral distribution (92%) but peripheral distribution alone was very limited (8%) (P = 0.0001). Glut1 positivity was associated with depth of invasion (P = 0.0001), lymphatic permeation (P = 0.0001), venous invasion (P = 0.0001), lymph node metastasis (P = 0.0001), hepatic metastasis (P = 0.0001), and carcinoma stage (P = 0.0001). However, peritoneal dissemination was not found to be associated with Glut1 positivity (P = 0.0833). The survival of patients who had tumors that expressed Glut1 was significantly shorter than that of patients with Glut1-negative tumors (P = 0.0001).
In human gastric carcinoma, Glut1 is expressed late in carcinogesis and increases with disease progression. Glut1 expression is associated with tumor aggressiveness and patient survival.
Cancer 09/2001; 92(3):634-41. · 4.77 Impact Factor
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ABSTRACT: Two cases of nasal tumors with pericytic myoid differentiation are reported. The tumors occurred in a 77-year-old woman and a 60-year-old man as polypoid lesions covered by normal mucosa. Histologically, the tumors were composed of uniform short spindle or stellate cells with indistinct cell borders arranged in narrow and short fascicles. Numerous blood vessels of various sizes were common in both cases. The tumor cells of both cases stained intensely with anti-vimentin and anti-actin antibodies, but not with anti-desmin, CD34, or anti-high-molecular-weight caldesmon antibodies. Ultrastructural examination revealed well-developed actin thin filaments with dense bodies, subplasmalemmal plaques, intercellular junctions, and irregular discontinuous basement membranes. These histopathologic features suggest true pericytic differentiation of the tumors (true hemangiopericytoma), unlike soft tissue-type hemangiopericytoma. Generally, sinonasal hemangiopericytomas are subdivided into soft tissue-type hemangiopericytomas and true hemangiopericytomas identical to the cases presented here. Soft tissue-type hemangiopericytomas are frequently highly aggressive, whereas true hemangiopericytomas show localized benign behavior. Sinonasal true hemangiopericytomas should be strictly differentiated from soft tissue-type hemangiopericytomas.
Archives of pathology & laboratory medicine 06/2001; 125(5):686-90. · 2.58 Impact Factor
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ABSTRACT: The expression of fatty acid synthase (FAS), an enzyme necessary for de novo fatty acid synthesis, has been examined in several types of tumours so far, but not in oesophageal cancer and dysplasia.
We examined the immunohistochemical reactivity of FAS in 4 normal adult oesophagi, 14 dysplastic oesophageal lesions, and 80 squamous cell carcinomas and 6 cases with 4 special types of malignancies of the oesophagus. We also analysed the correlation between FAS expression and various clinicopathological features and long-term survival in patients with oesophageal cancer.
In the normal oesophagus, only faint cytoplasmic FAS expression was observed in cells of the basal layer. In contrast, FAS-positive cells were found in 92.9% of cases of dysplasia and 96.5% of cases of carcinoma including 6 cases with a specific histological subtype. However, high expression of FAS did not correlate with either clinicopathological features or prognosis of patients with oesophageal cancer.
Our results demonstrate that FAS is expressed in almost all oesophageal carcinomas of both usual and special types and dysplastic lesions, suggesting that FAS may be upregulated continuously from the early stage of oesophageal squamous cell carcinogenesis to established carcinoma.
Pathobiology 02/2001; 69(6):297-303. · 1.18 Impact Factor
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Nihon Naika Gakkai Zasshi 01/2001; 89(12):2531-3.
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ABSTRACT: Although inflammatory myofibroblastic tumors, originally described in the lung, have recently been recognized to occur in various sites, their origin in bone is exceptional. We present a case of inflammatory myofibroblastic tumor, so-called inflammatory fibrosarcoma, of the bone. The tumor occurred in the iliac bone of a 70-year-old woman. Standard radiographs and magnetic resonance imaging revealed a destructive bone tumor that expanded into the soft tissue. Although the patient underwent excision of the hemi-iliac bone, multiple pulmonary metastases were noted 1 year after the operation. On histologic examination, the tumor was found to be composed of a sarcoma-like cellular area and a hypocellular fibrous area. Inflammatory cell infiltration into the tumor was a distinctive feature and is analogous with that of conventional inflammatory myofibroblastic tumor or inflammatory fibrosarcoma of the soft tissue. This is the first report to our knowledge of an inflammatory myofibroblastic tumor of the bone with distant metastasis.
Archives of pathology & laboratory medicine 11/2000; 124(10):1514-7. · 2.58 Impact Factor
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J Takeda,
Y Sato,
H Kiyosawa,
T Mori,
S Yokoya,
A Irisawa,
M Miyata,
K Obara,
T Fujita, T Suzuki,
R Kasukawa,
A Wanaka
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ABSTRACT: Endogenous retroviral gene products have been recognized as being expressed in human cancerous tissues. However, these products have not been shown to be antigenic targets for T-cells, possibly due to immune tolerance. Since carcinogen-induced colon tumor CT26 expresses an envelope protein, gp70, of an endogenous ecotropic murine leukemia virus that is comparable to human tumor-associated antigens, we examined whether a DNA vaccine containing the gp70 gene induces protective immunity against CT26 cells. Injection of mice with plasmid DNA (pDNA) encoding gp70 alone failed to induce anti-gp70 antibody (Ab) or anti-CT26 cytotoxic T lymphocyte (CTL) responses. However, immunization with pDNA encoding the beta-galactosidase (beta-gal)/gp70 fusion protein induced anti-gp70 Ab and anti-CT26 CTL responses and conferred protective immunity against CT26 cells. These results indicate that beta-gal acts as an immunogenic carrier protein that helps in the induction of immune responses against the poorly immunogenic gp70. Considering these results, it is possible that potential tolerance to the endogenous retroviral gene products expressed by human tumors may be overcome by DNA vaccines that contain an endogenous retroviral gene fused to genes encoding immunogenic carrier proteins.
Cellular Immunology 09/2000; 204(1):11-8. · 1.97 Impact Factor
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A Takahashi, T Suzuki,
S Shishido,
J Tojo,
O Ito,
Y Kazuta,
H Watanabe,
H Ishikawa,
H Ohira,
K Obara,
R Kasukawa
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 07/2000; 97(6):723-8.
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ABSTRACT: Animal fatty acid synthase (FAS) is a homodimer protein which synthesizes long-chain fatty acids and is rich in liver, brain, breast, and lung. However, the precise cellular localization of FAS in human tissues has not been elucidated. Immunohistochemistry with a new antibody to human FAS revealed that in adult human tissues FAS is distributed mainly in cells with high lipid metabolism (adipocytes, corpus luteum, hepatocytes, sebaceous glands, and Type II alveolar cells), in hormone-sensitive cells (anterior pituitary, apocrine gland, breast, endometrium, prostate, seminal vesicle, and adrenal cortex), and in a subset of epithelial cells of duodenum and stomach, colon absorptive cells, cerebral neurons, basket cells of cerebellum, decidua, uroepithelium, and epidymis. In fetal cells at 20 weeks of gestation, FAS was mainly present in proliferative epithelial cells of the digestive and respiratory systems, proximal renal tubules, adrenocortical cells, and mesenchymal and hematolymphoid cells. Staining was significant in nonproliferating cells, as observed in adult, and in sympathetic ganglion cells, Leidig cells of testis, and Langhans cells of chorionic villi. FAS is maintained in hormone-sensitive cells and/or cells active in lipid metabolism in the adult and is expressed in proliferating cells in the fetus, suggesting active fatty acid synthesis for energy utilization or membrane lipids.
Journal of Histochemistry and Cytochemistry 06/2000; 48(5):613-22. · 2.72 Impact Factor
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ABSTRACT: A case of clear cell sarcoma (CCS) arising in the transverse colon is presented. The tumor consisted of sheets or small nests of epithelioid malignant cells possessing pleomorphic nuclei with one or more prominent nucleoli and ample clear or slightly eosinophilic cytoplasm. Some of the tumor cells contained various amounts of melanin pigments that were confirmed by histochemical and ultrastructural examinations. Immunohistochemical examination showed a positive immunoreactivity for HMB45 and S-100 protein. A metastatic nodule, which was found 9 months after surgery, showed similar histological findings to those of the primary one but lacked melanin pigments. Reverse transcriptase- polymerase chain reaction using total ribonucleic acid obtained from metastatic nodule demonstrated the presence of EWS-ATF-1 fusion gene. Based on these findings, the present case tumor is a CCS of the colon.
Pathology International 06/2000; 50(5):412-6. · 1.62 Impact Factor
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ABSTRACT: Caldesmon is a protein widely distributed in smooth and non-smooth muscle cells and is thought to regulate cellular contraction. Its isoform, high-molecular-weight caldesmon (h-CD), was demonstrated to be specific for smooth muscle cells and smooth muscle tumors of the soft tissue and to never be expressed in myofibroblasts. We performed an immunohistochemical study to examine h-CD expression in the following bone tumors: conventional and non-conventional osteosarcoma, 13; malignant fibrous histiocytoma of bone, 5; giant cell tumors of bone, 5; chondroblastoma, 3; metastatic leiomyosarcoma, 2; and rhabdomyosarcoma, 1. Frequent immunoreactivity for muscle actin (alpha-smooth muscle actin or muscle-specific actin) was seen in 11 of 13 osteosarcomas and all other tumors, whereas h-CD was expressed intensely only in 2 leiomyosarcomas. h-CD is considered a specific and useful marker to distinguish smooth muscle tumor from bone tumors with myoid differentiation.
American Journal of Clinical Pathology 06/2000; 113(5):663-8. · 2.60 Impact Factor
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ABSTRACT: Five cases of non-melanotic pigmented schwannoma with excess accumulation of neuromelanin are presented. The tumors were composed basically of spindle or fusiform tumor cells, compatible with those of classical schwannoma, together with varying numbers of tumor cells containing various amounts of light brown or grayish pigment. Fontana-Masson stain demonstrated argentaffin granules in some tumor cells of each tumor and bleaching with potassium permanganate abolished argentaffin reaction. Ultrastructural examination demonstrated the granules contained fine particles with heterogeneous density, occasionally together with coarse granular materials or amorphous high-density areas, indicating lysosome or autophagosome. Neither typical melanosomes nor neurosecretory granules were detected. In immunohistochemistry, neurogenic markers as well as CD68 were expressed in most tumor cells in each case and various numbers of tumor cells were positive for Leu7 and CD34. Lysozyme was also frequently positive in tumor cells, especially in granular cells. HMB45 was not expressed in any of the cases. These findings indicate that these cases are schwannomas with abnormal accumulation of neuromelanin-like pigment.
Pathology International 04/2000; 50(3):230-7. · 1.62 Impact Factor
