Valenti M T, Azzarello G, Vinante O, Manconi R, Balducci E, Guidolin D, Chiavegato A, Sartore S
Department of Medical Oncology, U.L.S.S. 13, Noale, Venice, Italy.
J Cancer Res Clin Oncol. 1998;124(2):93-105. doi: 10.1007/s004320050140.
A comparative analysis of the differentiation pattern, the proliferative behaviour, and the level of apoptosis between human benign and malignant neoplasms of smooth-muscle (SM) tissue is lacking. The clinical, histopathological, immunochemical, and immunocytochemical features of leiomyomas (LM) and leiomyosarcomas (LMS) were investigated by a panel of monoclonal antibodies specific for some differentiation markers of SM tissue (SM myosin and alpha-actin, desmin, and SM22) and for markers of non-muscle tissue (vimentin and non-muscle myosin). Proliferating normal and neoplastic cells were identified by proliferating-cell nuclear antigen (PCNA)/Ki67 immunostainings and the apoptotic cells were revealed by means of the terminal-deoxynucleotidyltransferase-mediated dUTP nick-end labelling technique. Gel electrophoresis and Western blotting, performed with anti-(SM1/SM2 myosin isoform) antibody, indicated quantitative differences between LMS and LM, which mirrored higher positive to negative nuclear ratios for PCNA, Ki67 and apoptosis in malignant as opposed to benign neoplasms. With LM, however, a similar SM1 to SM2 ratio could be associated with different proliferation levels. Uterine, gastric and intestinal LMS displayed specific patterns of SM1/SM2 and/or non-muscle myosin expression that were not paralleled by different levels of proliferation/apoptosis. While the level of PCNA/Ki67 correlated with the level of apoptosis in normal SM tissues and LM, that of LMS did not. In vivo at the cellular level, LM and uterine LMS displayed a near-uniform SM tissue differentiation, whereas the other LMS displayed a lesser or a heterogeneous immunoreactivity. In vitro, cultured LMS cells showed a limited and peculiar expression of SM myosin. In conclusion, there is no reciprocal relationship between degree of differentiation and the level of proliferation, as exemplified by the finding that the less differentiated intestinal LMS displays the lowest proliferative behaviour and that the relatively more differentiated gastric LMS/metastasis is more proliferative.
目前尚缺乏对人类平滑肌（SM）组织良性和恶性肿瘤之间分化模式、增殖行为及凋亡水平的比较分析。通过一组针对SM组织某些分化标志物（SM肌球蛋白和α-肌动蛋白、结蛋白和SM22）以及非肌肉组织标志物（波形蛋白和非肌肉肌球蛋白）的单克隆抗体，研究了平滑肌瘤（LM）和平滑肌肉瘤（LMS）的临床、组织病理学、免疫化学及免疫细胞化学特征。通过增殖细胞核抗原（PCNA）/Ki67免疫染色鉴定增殖的正常细胞和肿瘤细胞，采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记技术显示凋亡细胞。用抗（SM1/SM2肌球蛋白异构体）抗体进行的凝胶电泳和蛋白质印迹分析表明，LMS和LM之间存在定量差异，这反映出恶性肿瘤与良性肿瘤相比，PCNA、Ki67和凋亡的核阳性与阴性比率更高。然而，在LM中，相似的SM1与SM2比率可能与不同的增殖水平相关。子宫、胃和肠道LMS表现出SM1/SM2和/或非肌肉肌球蛋白表达的特定模式，而增殖/凋亡水平不同则与之不平行。虽然PCNA/Ki67水平与正常SM组织和LM中的凋亡水平相关，但LMS并非如此。在体内细胞水平，LM和子宫LMS表现出近乎一致的SM组织分化，而其他LMS表现出较弱或异质性的免疫反应性。在体外，培养的LMS细胞显示出SM肌球蛋白的有限且特殊的表达。总之，分化程度与增殖水平之间不存在相互关系，例如，分化程度较低的肠道LMS表现出最低的增殖行为，而分化程度相对较高的胃LMS/转移灶增殖性更强这一发现就证明了这一点。
