Hidenari Kusakabe

Prognostic significance of dysadherin expression in epithelioid sarcoma and its diagnostic utility in distinguishing epithelioid sarcoma from malignant rhabdoid tumor

Dysadherin is a cancer-associated cell membrane glycoprotein, which downregulates E-cadherin and promotes metastasis. We studied the clinicopathological features in 72 cases of epithelioid sarcoma and in six cases of malignant rhabdoid tumor, and also assessed the immunohistochemical expression of dysadherin, E-cadherin and MIB-1 in epithelioid sarcoma and malignant rhabdoid tumor cases. In addition, we compared dysadherin mRNA expression between epithelioid sarcoma and malignant rhabdoid tumor cell lines, using RT-PCR and real-time quantitative RT-PCR analysis. Immunohistochemical dysadherin expression was more frequently observed in proximal-type epithelioid sarcoma (71%) in comparison with distal-type epithelioid sarcoma (36%) (P=0.037). Furthermore, seven proximal-type epithelioid sarcoma cases mimicking malignant rhabdoid tumor (histologically classified as the large cell type, accompanied by frequent rhabdoid cells and located in deep soft tissue) were all positive for dysadherin (100%), whereas dysadherin expression was not detected at all in any of the true six malignant rhabdoid tumors (0%). Cell lines established from proximal-type epithelioid sarcoma revealed significantly higher levels of dysadherin mRNA expression, compared with the levels seen in malignant rhabdoid tumor cell lines by real-time quantitative RT-PCR (P=0.0433). Epithelioid sarcoma patients with dysadherin expression survived for a significantly shorter time than those without dysadherin expression (P=0.001). In multivariate analysis, dysadherin immunopositivity (P=0.0004) was one of the two independent adverse prognostic factors. We conclude that dysadherin expression in epithelioid sarcoma is a significant poor prognostic factor and that it is a powerful diagnostic marker for distinguishing epithelioid sarcoma, including the proximal-type epithelioid sarcoma, from malignant rhabdoid tumor. In epithelioid sarcoma, especially in proximal-type epithelioid sarcoma, increased cell disadhesion and motility by dysadherin plays an important role to acquire aggressive biological behavior. However, in malignant rhabdoid tumor, cell growth cycle that is regulated by hSNF5/INI1 gene seems to be critical to lethal biological behavior rather than dysadherin.

A Case of Syringocystadenocarcinoma Papilliferum In situ Occurring Partially in Syringocystadenoma Papilliferum

We report a case of syringocystadenocarcinoma papilliferum in situ associated with syringocystadenoma papilliferum. The patient was a 64‐year‐old man with a red tumor that arose on top of his head two years before he consulted our department. The histological findings revealed a papillomatous growth on the epidermis forming several invaginations. Numerous papillary projections, lined by a two‐layered epithelium with a benign appearance and decapitations on the luminal surface of the cells, extended into the lumens of the invaginations. Some projections showed a disorderly arrangement of multilayered cells with atypical nuclei. No differences between findings in the syringocystadenocarcinoma papilliferum in situ and those in the syringocystadenoma papilliferum were observed histochemically (PAS) or immunohistochemically (cytokeratin, CEA, CA 19–9, S‐100, gross cystic disease fluid protein, lysozyme and Leu M1).

p53 gene mutations in squamous cell carcinoma occurring in scars: comparison with p53 protein immunoreactivity.

We determined the relationship between p53 expression and p53 gene mutations in squamous cell carcinoma occurring in scars and unrelated to UV light irradiation. We analyzed biopsy specimens obtained from three patients with squamous cell carcinoma. A monoclonal antibody against p53 (DO-7) was used for the immunohistochemical analysis. p53 gene mutations were detected by the polymerase chain reaction and single-strand conformation polymorphism analysis and direct DNA sequencing. p53 overexpression was observed in atypical squamous cells of one case. Those of two other cases, however, showed negative immunoreactivity to p53. Exon 6 of the p53 gene in all three cases and exon 7 in one case showed electrophoretic mobility shifts in polymerase chain reaction and single-strand conformation polymorphism analysis. DNA sequencing analysis showed a missense mutation and a silent mutation in exon 6 of the case with p53 overexpression, a three-base deletion in exon 6 of one case with no p53 overexpression, and a three-base deletion in exon 6 and a missense mutation in exon 7 of another such case. Although immunohistochemical overexpression of p53 has been thought to result from p53 gene mutations, our results suggest that negative immunoreactivity to p53 also can result from p53 gene mutations, for example, short gene deletions.

Metastatic epithelioid sarcoma with an N-ras oncogene mutation.

At age 25 a Japanese woman noticed an elastic-hard nodule 2 cm in diameter on the anterior side of her right leg. The nodule had developed an ulcer in its center. Simple resection was performed several times. However, the lesion recurred repeatedly. The patient underwent amputation of the right leg at the age of 34, because the diagnosis of epithelioid sarcoma was established histologically. No recurrence was observed for 9 years. Recently, the patient noticed multiple painful, ulcerative nodules about 1 cm in diameter on her scalp, trunk, and extremities. She refused extensive resection for a religious reason and died of massive hematemesis. Autopsy revealed metastatic epithelioid sarcoma in the skin, lungs, kidneys, pancreas, transverse colon, thyroid, and sternum. Chromosomal analysis of the tumor revealed various aberrations and an N-ras oncogene mutation.

Expression of lung resistance protein in epithelioid sarcoma in vitro and in vivo

Abstract The incidence of epithelioid sarcoma among patients with malignant soft tissue tumors is small, but the rates of recurrence and metastasis of this type of sarcoma are high. To date, effective chemotherapy for advanced epithelioid sarcoma has not been established and, furthermore, epithelioid sarcoma is known to exhibit multidrug resistance (MDR). The chemosensitivities to anticancer agents of two cell lines established from epithelioid sarcoma were examined in this study. The results showed that the ES-OMC-MN and SFT-8606 cell lines were resistant to vincristine (IC 50 1190 n M and 872 n M , respectively) and Adriamycin (IC 50 921 n M and 650 n M , respectively), but sensitive to actinomycin D (IC 50 < 10 n M ). P-glycoprotein (p-Gp) and MDR-associated protein (MRP) were not expressed in these cell lines, but a high expression level of lung resistance protein (LRP) was observed. The original tumor tissues from which the two cell lines were established were also found to be LRP-positive but not to express p-Gp or MRP. Their chemosensitivities to Adriamycin were not significantly altered in the presence of 2.5 μg/ml anti-LRP antibody (LRP-56), but the IC 50 of vincristine was much less (IC 50 128 n M and 27 n M , respectively) than that for an untreated cell line. It is thus suggested that the vincristine resistance in the two cell lines is LRP-mediated. Since cyclosporin A, known to be a modifier of p-Gp, also induced reversal of vincristine resistance in the ES-OMC-MN and SFT-8606 cell lines (IC 50 6.2 n M and 17 n M , respectively), it is suggested that cyclosporin A acts as a modifier of MDR mediated by LRP.

Establishment and characterization of an epithelioid sarcoma cell line with an autocrine response to interleukin-6

A novel epithelioid sarcoma (ES) cell line, designated as ES-OMC-MN, was established from a 44-year-old woman with recurrence and metastasis of ES. The cells were spindle-shaped or polygonal and were positive for cytokeratin and vimentin on immunohistochemical staining. Electron microscopy revealed desmosome-like structures between the cells. These characteristics were also noted in the original tumor. Southern blot analysis of HindIII digests showed an additional 8.0 kb band and an 8.8 kb band in DNA from the cultured cells and the original tumor as well as the peripheral blood cells of the patient, while only an 8.8 kb band was observed in control human placental DNA. There were no point mutations of N-ras codons 12, 13, and 61, suggesting that the abnormality of N-ras was not due to mutation but to polymorphism. Interleukin-6 (IL-6) was secreted into the culture medium at high levels. Recombinant IL-6 augmented the proliferation of these cells, while cell growth was inhibited by incubation with an anti-IL-6 antibody. The cells also expressed surface IL-6 receptors, indicating that IL-6 acted on this cell line in an autocrine manner. IL-6 and IL-6 receptors were also found in the original tumor. These results demonstrate that ES-OMC-MN cells retained all the morphological and biochemical characteristics of the original tumor and suggest that an autocrine effect of IL-6 may be involved in the development of ES.

Acute Monocytic Leukemia Presenting as Cutaneous Involvement

Specific cutaneous lesions appearing during acute monocytic leukemia (AMoL) are more frequent than those associated with other types of leukemia. However, skin involvement preceding the presence of leukemic cells in the peripheral blood is quite rare. In this paper, we describe a case where a 25-year-old male had multiple infiltrative erythemas and nodules on his arms. Histologically, the nodules were formed by masses of tumor cells in the dermis. Peripheral-blood tests revealed no abnormalities, but bone marrow aspiration from the sternum led to a diagnosis of AMoL. The diagnosis of specific cutaneous lesions of AMoL was confirmed by the results of cytochemical studies of bone marrow smears, and cutaneous nodules of cutaneous biopsy specimens led to early diagnosis. Complete remission was achieved with combination chemotherapy and peripheral blood stem cell transplantation.

A case of partial spontaneous regression of Bowen's disease

Bowen病は1912年, Bowenが表皮内限局型有棘細胞増殖を示す例を前癌病変として発表したことに端を発するが, 本体は表皮内有棘細胞癌である。成長速度は緩徐で稀に自然消退を示すことがある。予後は悪くないが時に浸潤転移を来す。今回我々は30年来の病変に自然消退傾向を認めたBowen病の1例を経験したので, 若干の考察を加えて報告する。

A case of liposarcoma in the face.

Liposarcoma in the face region is extremely rare. We reported a case of recurrent liposarcoma of the right cheek of a 54-year-old man. He received first tumor excision in another hospital in May, 1994. In the histologic examination, the tumor mass consisit of lipoblast, uniformly shaped, small round microvacuolated cells containing atypical hyperchromatic vesicular nuclei were present from lower dermis to subctaneous tissue. The histopathologic classification was round cell type. Partially, transitions toward the myxoid type and screlosing type were present. One year later, local recurrence occured, but there was no metastasis. Second wide local excision was performed in June, 1995. Few changes occured in the histological findings of the second excision and it revealed round cell type.

Epithelioid sarcoma recurring in wide extirpation after 9 years and recognizing the reconstitution of N-ras genes.

A 43-year-old-woman developed an elastic, hard node (2cm in diameter) on the anterior side of the right leg. The lesion was left untreated, until an ulcer had formed in its center. Simple resection was performed several times. However, the lesion recurred repeatedly. Based on a histopathological diagnosis of epithelioid sarcoma, the woman underwent amputation of the right leg 9 years ago. For 9 years after surgery, no recurrence was observed. The patient recently developed multiple painful ulcerative nodes (about 1cm in diameter) on the head, trunk and extremities. Because the patient refused extensive resection for religious reasons, local OK-432 therapy and high-dose cepharanthin therapy have been performed. Node formation is still continuing. Chromosomal analysis of removed tissue revealed various aberrations and N-ras oncogene rearrangement was detected.