Two Autopsy Cases of Primary Leiomyosarcoma of the Liver Superiority of Muscle‐specific Actin Immunoreactivity in Diagnosis
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Abstract:
Two autopsy cases of leiomyosarcoma of the liver in a 49‐year old female and 63‐year‐old male are reported. Both of the liver tumors showed electron microscopically dense patches in the cytoplasm and intermediate junctions between the tumor cells, suggesting a smooth muscle cell origin, irrespective of their different histological features. The nature of both tumors was confirmed by positive immunoreactivity for muscle‐specific actin in the tumor cells, whereas desmin immunoreactivity was labile in both cases, showing a higher diagnostic value of the former compared with the latter in these leiomyosarcomas. Both cases, showed extensive distant metastases in spite of an evident difference in their mitotic indices, indicating that this index is not reliable for judging the metastatic potential of these tumors. Acta Pathol Jpn 41: 461–465, 1991.Keywords:
Desmin
Mitotic index
중간세사단백인 desmin은 성숙한 근성유의 세포골격을 이루며 Vnnentin은 근재생시 중간엽기원 세포에 나타나기 때문에 중간세사단액의 발현여부로 근재생과정을 주석할 수 있다 신경성근영총에 따른 근재생과정을 중간세사의 변화로 알아보고자 흰쥐의 좌골신경을 압궤손상시킨 후 시기별 (2 4 6, 15 20, 27, 69일)로 장딴지근을 정취해 냉동연속조직절편을 제작한 뒤 연역조직화학적 반응을 시켜 desmin 및 Vlmentin 의 발현변화를 조사하여 다음과 같은 결과를 얻었다
l. 정상적인 흰쥐 장딴지근의 근섬유에서 desmin은 약하게 반응한 반연 Vlmentm 은 반응이 없었고 신경 손상 후 2, 4일째까지 같은 현상을 보였다.
2. 신경 손상후 6일째에 처음으로 desmin과 Vlmentin 에 모두 강한 양성연역반응을 보이는 위축된 근섬유들이 관찰되었다.
3. 신경손상 후 15일째에서 위축왼 근섬유을이 증가되었고 정상 근성유보다 desmm 에 강한 면역반응성을 나타내었다. Desmin과 vlmentm 모두에 양성반응율 보인 위쭉왼 근섬유들이 소수 관찰되었다.
4. 신경손상 후 20일째에서 대부분의 근섬유들이 정상 근성유 보다 너 강한 desmin 양성연역반응을 보였다. 일부 근섬유들은 중심핵을 갖고 있었으며 desmin과 Vimentin에 대한 양성연역반응을 동시에 나타내었다
5. 신경손상 후 27일째에서 대부분의 근섬유들은 정상 크기로 회복되었으나 소수의 근섬유들은 위축된 상태였다 위축된 근섬유은 desmin에는 반응성을 보이지 않은 반면 Vlmentm 에 매해서는 은섬유의 일부가 양성반응을 나타내였다.
6. 신경손상후 69일째에서 비대된 근섬유가 많이 관찰되였고 desmin 및 vinentin에 대한 면역반응은 정상근섬유와 동일하였다. 일부 위축된 근섬유들은 desmin 에 양성 면역반응을 보였으나 Vlmentm 에는 양성 면역반응을 보인 근섬유는 관찰되지 않았다.
위의 결과로 미루어 볼 때 약한 desmm 반응 만을 보이는 은섬유는 정상 강한 desmm잔응만을 나타내는 근섬유는 변성 (degeneration), desmm 과 Vlmentm 이 동시에 나타내는 근섬유는 재생 (regenerahon) 중인 근섬유라고 규정지을 수 있겠다 그러므로 중간세사 단액인 desmin 과 Vlinentm 발현 어부로 신경성근육병증에는 물론 다양한 근육병증의 진단 및 근육발생에도 유용하게 이용될 수 있을 것으로 사료된다.
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Desmin is one of five major intermediate filament proteins in cardiomyocytes. Desmin contributes to the maintenance of healthy muscle. The desmin content in cardiomyocytes directly affects the long-term prognosis of patients with heart failure, and lack of desmin leads to myocyte contractile dysfunction. However, the mechanism is elusive. In this study, we measured desmin expression using western blotting and qPCR in the failed hearts of human patients and rats. Our results showed that desmin content was reduced at the protein level in failed hearts and isolated cardiomyocytes. The association of desmin and the gap junction proteins connexin 43 (Cx43) and zonula occludens-1 (ZO-1) was also investigated. Immunoprecipitation assay showed that desmin was associated with Cx43 in cardiomyocytes. To compare the electrical integration of skeletal myoblasts in cocultures with cardiac myocytes, familial amyloid polyneuropathy (FAP) activation rate was found in 33% desmin overexpressing skeletal myoblasts. Desmin not only affected Cx43 and ZO-1 expression but also facilitated the complex of Cx43 and ZO-1 in skeletal myoblasts, which enhanced cell-to-cell electrical coupling of skeletal myoblasts with cardiac myocytes. Desmin has potential as a novel therapeutic target for heart failure. Preservation of desmin may attenuate heart failure.
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The experimental material consisted of 20 dogs: 15 Doberman pinschers with diagnosed dilated cardiomyopathy (DCM), and five healthy dogs (three mixed breeds, one Doberman pinscher, one Boxer). DCM was confirmed by electrocardiography and echocardiography before euthanasia. After euthanasia, an autopsy was performed and myocardial samples were collected from the right and left ventricles, intraventricle septum, and right and left atrium. The samples for the histopathological and immunohistochemical analysis were fixed in with 7% formalin in PBS buffer. The presence of desmin was semiquantitatively evaluated under a light microscope. The normal levels of desmin expression in immunohistochemical staining were observed only in the control dogs. The desmin expression was elevated in 15 dogs with severe DCM The immunochemical method allowed for the evaluation of desmin activity in cardiomyocytes, and showed three patterns of its expression (increase expression, decrease expression, heterogeneous expression). The desmin expression was abnormal in the myocardial samples in dogs with DCM. We observed an increase expression of desmin in 10 dogs with moderate and a decrease expression of desmin in five dogs with advanced DCM. The relationship between the desmin expression and the progression of heart failure secondary to DCM requires further studies.
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A porcine antibody was used to clarify the localization of desmin filaments in the swine longissimus muscle by post-embedding immuno-electron microscopy. The major site of desmin localization was the bundle of filaments connecting Z-discs of adjacent myofibrils. These desmin filaments were localized not only between but also within myofibrils. This indicates that there exist more complicated networks rather than simple bundles of desmin filaments running parallel to the Z-discs. Clarification of desmin distribution within the myofibrils surrounding Z-discs provides a basic concept for consideration of the combination and transformation of vimentin to desmin in developing human embryonic muscles.
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