横纹肌肉瘤与胚胎横纹肌的形态学和免疫组织化学对…

对确诊的５０例横纹肌肉瘤（ＲＭＳ）和２０例不同胎龄的横纹肌，应用ＨＥ和Ｖｉｍｅｎｔｉｎ、Ｄｅｓｍｉｎ、ＨＨＦ－３５及Ｍｙｏｇｌｏｂｉｎ免疫标记进行了细胞形态学比较，发现其表达顺序和反应强度与肿瘤分化程度及胚胎横纹肌细胞发育一致。并依据瘤细胞成熟程度，提出了各型ＲＭＳ是由不同分化的瘤细胞组成，均系来自向横纹肌分化的原始间叶细胞。组织学分型主张既保留ＷＨＯ组织分型，同时各型中也能反应瘤细胞的分化程度。     

转化生长因子β1及其受体在横纹肌肉瘤中的表达

目的 :探讨横纹肌肉瘤 (RMS)中转化生长因子 β1(TGFβ1)及其Ⅰ、Ⅱ型受体 (TGFβRⅠ ,TGFβRⅡ )表达及其意义。 方法 :应用免疫组化技术 (S P法 )检测 4 9例经电镜或 (和 )免疫组化证实的横纹肌肉瘤及 2 0例正常横纹肌组织中的TGFβ1、TGFβRⅠ和TGFβRⅡ表达水平 ,并结合临床病理资料进行分析。 结果 :TGFβ1在RMS中的高表达率高于正常横纹肌组织 (P<0 0 1) ;TGFβRⅠ、TGFβRⅡ在 98% (48/ 4 9)的RMS及所有正常横纹肌组织中均有表达 ,两组无差异。TGFβ1表达与肌球蛋白重链呈负相关 (r=- 0 6 6 1,P <0 0 1)。TGFβ1在低分化组高表达率为 79% ,高分化组为 38%。 结论 :横纹肌肉瘤中存在TGFβ1自分泌和旁分泌现象 ,且肿瘤细胞表达相关受体。TGFβ1的表达与肌源性分化程度有关。TGFβ1信号传导途径可能参与了横纹肌肉瘤的发展与演进     

118例横纹肌肉瘤的临床病理和免疫组织化学研究

118 cases of rhabdomyosarcoma are reported. Specimens from 30 of these cases were stained with Masson Trichrome and phosphotunstic acid haemotoxylin. 36 cases were studied immunohistochemically by PAP, and ABC methods. Specific antibodies against myoglobin, desmin and vimentim were used. Positive immunostaining for myoglobin and desmin was found in 72.7% and 55.5% of the cases studied respectively. The positivity was dependent on the degree of cell differentiation. Results suggest that immunohistochemistry is a useful tool for the diagnosis of poorly differentiated rhabdomyosarcomas. Cross--striations were found in only 6 of the thirty cases (20%). It is now generally accepted that demonstration of cross--striations is not essential for the diagnosis; nevertheless, the characteristic features of fibrillary material arranged in whorls around the nucleus are of diagnostic significance. Histologically, it is also believed that searching for early differentiated rhabdomyoblasts combined with the histological pattern is of vital importance for an accurate diagnosis.     

中耳横纹肌肉瘤的免疫组织化学观察

横纹肌肉瘤（ｒｈａｂｄｏｍｙｏｓａｒｃｏｍａ,ＲＭＳ）为小儿最常见软组织恶性肿瘤,以头颈部,泌尿生殖道及躯干四肢多见,但中耳ＲＭＳ少见［１３］,临床上多表现为中耳炎、面神经麻痹和外耳道息肉等,临床早期诊断困难,我们对１０例中耳ＲＭＳ的临床病理及免疫...     

硬化性横纹肌肉瘤的临床病理学分析

目的探讨硬化性横纹肌肉瘤（SRMS）的临床病理学特征,以及与胚胎性横纹肌肉瘤（ERMS）和腺泡状横纹肌肉瘤（ARMS）之间的关系。方法观察4例SRMS的临床特点、光镜形态,以免疫组织化学染色[En Vision法;波形蛋白、结蛋白、α-平滑肌肌动蛋白（α-SMA）、肌特异性肌动蛋白（MSA）、生肌蛋白、肌调节蛋白（MyoD1）、高分子量钙调结合蛋白（h-CALD）、CD31、CD34、第Ⅷ因子相关抗原、S-100蛋白、细胞角蛋白（AE1／AE3）和问变性大细胞淋巴瘤激酶（ALK1）]确定免疫学表型。结果4例均发生于成年人,平均年龄41．5岁。男性2例,女性2例。肿瘤分别位于左腕部、右大腿、右颊部和右面部,直径大小为2．5—10．0cm,平均5．7cm。镜下以含有大量玻璃样变的基质为特征,类似原始的骨样组织或软骨样基质。瘤细胞主要由原始的小圆形细胞组成,其排列方式呈多样化,包括条束状、索状、列兵样、梁状、微腺泡状和假血管样排列等。除1例可见少量的横纹肌母细胞外,其余3例均未见横纹肌母细胞,也未见花环状多核巨细胞。2例的局部区域还含有梭形细胞成分,其中1例类似梭形细胞横纹肌肉瘤,另1例类似周围神经肿瘤。免疫组织化学标记显示,瘤细胞弥漫强阳性表达MyoD1,而结蛋白多为灶性表达,生肌蛋白多为阴性或仅为灶性阳性。3例表达MSA,2例表达Ot-SMA,但不表达h-CALD。S-100蛋白、CD31和ALK1等标记均为阴性。结论SRMS在形态上和免疫学表型上与ERMS和ARMS均有所不同,但在细胞遗传学上与ERMS关系密切。熟悉SRMS的形态特征和免疫学表型有助于识别这种少见的横纹肌肉瘤亚型及与其他硬化性肿瘤相鉴别。     

41例横纹肌肉瘤的临床病理及电镜与免疫组化研究

我室1958年～1986年病理外检所遇到的横纹肌肉瘤41例,男性25例,女性16例,男:女为1.6∶1。发病高峰年龄为10岁以前组(占41.5%),并对10例诊断横纹肌肉瘤及9例疑似本病者做了肌红蛋白免疫组织化学(ABC法)染色观察,2例做了电镜观察。以上方法对判断横纹肌肉瘤具有特异性,根据我们的经验并结合文献复习对横纹肌肉瘤组织学分类补充了未分化和高分化二个亚型。     

儿童横纹肌肉瘤的临床病理研究

目的 探讨横纹肌肉瘤的临床病理、免疫组织化学、电镜特点。方法 对145例患儿(男97例,女48例,年龄4个月～13岁,平均4．2岁),用HE、免疫组织化学(LSAB法)和电镜技术进行观察。所用抗体有：波形蛋白、结蛋白、平滑肌肌动蛋白(SMA)、肌红蛋白、神经元特异性烯醇化酶(NSE)、CD99(12E7)、白细胞共同抗原(LCA)。结果 145例患儿中,100例随访1～20年。组织学分为胚胎性、葡萄状、梭形细胞型、腺泡状和实性型。5年存活率：葡萄状85％、梭形细胞型横纹肌肉瘤85％,胚胎性60％,腺泡状40％、实性型横纹肌肉瘤25％,预后最好的是梭形细胞型和葡萄状横纹肌肉瘤,预后次之的是胚胎性横纹肌肉瘤,预后差的是腺泡状和实性型横纹肌肉瘤;预后好的部位是膀胱和头颈部,预后差的部位是躯干四肢、腹膜后和盆腔;免疫组织化学：107例均表达波形蛋白,除NSE、CD99和LCA均阴性外,结蛋白、SMA和肌红蛋白阳性率分别为78％、75%和37％。15例肿瘤经电镜观察,其中10例发现有肌丝和肌节结构。结论 免疫组织化学和电镜检查有利于儿童横纹肌肉瘤的病理诊断和组织分型。     

横纹肌肉瘤中MDM2及p53基因表达的原位杂交检测

目的观察ＭＤＭ２、ｐ５３癌基因在横纹肌肉瘤（ＲＭＳ）发病中的作用及其与临床病理、预后间的关系。方法对确诊并有随访的３１例ＲＭＳ标本,用原位杂交技术进行ＭＤＭ２、ｐ５３定位观察。结果发现ＭＤＭ２及ｐ５３癌基因表达阳性率分别为７７４％（２４／３１例）和６６７％（２１／３１例）,其阳性率与年龄、性别和ＲＭＳ组织类型无明显关联（Ｐ＞０．０５）,但阳性率及其强度与ＲＭＳ分化程度（Ⅰ级与Ⅲ级）,转移与否及存活率差异有显著性（Ｐ＜０．０５）。结论ＭＤＭ２、ｐ５３阳性检出率有助于判断ＲＭＳ恶性程度及预测肿瘤的转移和预后。     

肺梭形细胞横纹肌肉瘤1例并文献复习

目的探讨成人梭形细胞横纹肌肉瘤(spindle cell rhabdomyosarcoma,SCRM)的临床病理学特征。方法回顾性分析1例肺内SCRM的临床病理学与免疫表型特征,并复习相关文献。结果患者男性,72岁,因咳嗽、胸闷2个月入院,胸部CT检查示右肺上叶见一巨大软组织肿块影。镜检:肿瘤无包膜,呈不规则束、片状排列,局部呈巢状结构,间质纤维组织增生。瘤细胞小圆形、梭形或上皮样,胞质稀少,胞核深染、染色质细颗粒状,部分可见核仁,核分裂象达25个/10 HPF,局部可见横纹肌母细胞。免疫表型:vimentin、desmin、Myogenin、CD56、CD99均阳性(阳性细胞数>50%),CK(AE1/AE3)、CK7、Syn、CgA、CD45、TTF-1、MyoD1、NSE、BCL-2、S-100蛋白均阴性,Ki-67增殖指数约60%。结论肺成人原发性SCRM临床罕见,组织学形态多样,预后较差,需与肺小细胞癌、滑膜肉瘤、淋巴瘤等鉴别。     

横纹肌肉瘤中小窝蛋白-3的表达及鉴别诊断意义

目的 研究小窝蛋白-3(caveolin-3)在横纹肌肉瘤(RMS)中的表达特点与鉴别诊断价值.方法 选取20例RMS、30例其它软组织肿瘤.用免疫组化SP法及原位杂交分别检测caveolin-3的蛋白和mRNA的表达水平.用免疫组化SP法分别检测20例RMS中desmin和myoD1蛋白的表达水平.结果 SP法caveolin-3蛋白在RMS阳性表达率为80%(16/20),其它软组织肿瘤皆为阴性(0/30),两者之间的表达差异具有统计学意义(P＜0.05).原位杂交在15例RMS中有13例检测到caveolin-3 mRNA表达,阳性表达率为86.7%(13/15),在26例其它软组织肿瘤中的阳性表达率为7.7%(2/26),两者之间的表达差异亦有统计学意义(P＜0.05).SP法RMS中desmin和myoD1蛋白的阳性率分别为84.2%(16/19)、89.5%(17/19),与caveolin-3蛋白的表达差异均无统计学意义(P＞0.05).结论 caveolin-3在RMS中的表达有较高的敏感度和特异性,可作为临床鉴别诊断RMS和其它软组织肿瘤的有用的新型标记物.     

Prognostic significance of the MDM2/HMGA2 ratio and histological tumor grade in dedifferentiated liposarcoma

Dedifferentiated liposarcoma (DDLPS) is a relatively common soft tissue sarcoma that results from the progression of well‐differentiated liposarcoma (WDLPS). This study aimed to investigate the progression process and to clarify the pathological and genetic factors related to poor prognosis in DDLPS. In 32 DDLPS cases and five WDLPS cases, genetic factors were analyzed by custom comparative genomic hybridization (CGH) array, which was designed to densely cover gene regions known to be frequently amplified in WD/DDLPS. The analyses comparing primary and metastatic lesions and those comparing histologically different areas in the same tumor revealed intra‐tumoral genetic heterogeneity and progression. According to a prognostic analysis comparing the good‐prognosis and the poor‐prognosis groups, we selected MDM2 and HMGA2 as candidate genes associated with poor and good prognosis, respectively. The ratios of the amplification or gain levels of MDM2 and HMGA2 expressed in log ratios (log[MDM2/HMGA2] = log[MDM2]‐log[HMGA2]) were significantly associated with prognosis. An amplification or gain level of MDM2 that was more than twice that of HMGA2 (MDM2/HMGA2 > 2, log[MDM2/HMGA2] > 1) was strongly related to poor OS (P < .001) and poor distant metastasis‐free survival (DMFS) (P < .001). In the pathological analysis of 44 cases of DDLPS, histological tumor grade, cellular atypia, and MDM2 immunoreactivity were related to overall survival (OS), while HMGA2 immunoreactivity tended to be associated with OS. Cellular atypia was also associated with DMFS. In conclusion, histological grade and MDM2 expression were determined to be prognostically important, and the MDM2/HMGA2 amplification or gain ratio was found to have significant prognostic value by the custom CGH array analysis.     

HMGA gene rearrangement is a recurrent somatic alteration in polypoid endometriosis

The pathogenesis of endometriosis is unclear, and several genetic, endocrine, immune, and environmental agents have been evaluated with no putative causative factors identified. Here, we show somatic genetic alterations involving HMGA1 (6p21) and HMGA2 (12q15) in 3 cases of polypoid endometriosis. The lesions involved the small bowel mesentery and perirectal soft tissue in 1 case and the posterior vaginal fornix and sigmoid colon serosa in 2 other cases, respectively. All had a polypoid configuration with cystically dilated irregular glands and fibrotic stroma, containing thick-walled vessels. Conventional cytogenetic analysis of 1 case showed 46,XX,t(5;12)(q13;q15) in all metaphases. Fluorescence in situ hybridization studies confirmed the balanced rearrangement of HMGA2. HMGA1 rearrangements were present in 2 additional cases. Rearrangements were exclusively found in the stromal component but not in the glandular component. These findings suggest that HMGA rearrangements likely contribute to the pathogenesis of endometriosis. However, additional studies are needed to better define the biologic role of this genetic alteration.     

Odontogenic myxofibroma with HMGA2 overexpression and HMGA2 rearrangement

Odontogenic myxofibromas are variants of odontogenic myxomas that contain considerable amounts of collagen fibers in the myxoid stroma. Cytogenetic studies of odontogenic myxomas/myxofibromas have rarely been reported. This report describes the first case of an odontogenic myxofibroma presenting with HMGA2 protein overexpression and HMGA2 rearrangement in a 40-year-old woman. A 2.7-cm tumor in the premolar region of the right mandible was curettaged. There was no evidence of recurrence or metastasis at 12 months after the surgery. Histological examination revealed that the tumor comprised spindle or stellate cells with mild nuclear pleomorphism, abundant myxoid matrix and partly dense collagen fibers. Mitotic figures were rarely observed. Immunohistochemically, the tumor cells were diffusely positive for vimentin and HMGA2. Less than 1% of the tumor cells were positive for Ki-67. We detected split signals by interphase fluorescence in situ hybridization (FISH) in paraffin sections using HMGA2 break-apart probes. The breaks were certainly located within or near the HMGA2 gene. No rearrangement of the FUS gene was detected by FISH, implying discrimination from low-grade fibromyxoid sarcoma. It is suggested that HMGA2 rearrangement and HMGA2 protein overexpression may be associated with the tumorigenesis of odontogenic myxomas/myxofibromas, similar to the case for many other benign mesenchymal tumors.     

胃癌中HMGA2与HDAC6表达的临床意义及其相关性

目的检测胃癌中高迁移率族蛋白2(HMGA2)和组蛋白去乙酰化酶6(HDAC6)在胃癌中的表达情况及相关关系,分析其与临床病理特征的关系。方法分别用免疫组织化学法、Western blot和real-time PCR检测82例配对人胃癌、癌旁及正常组织中HMGA2和HDAC6的蛋白及mRNA表达,并分析其与临床病理参数的关系及两者表达的相关性。结果胃癌组织中HMGA2和HDAC6蛋白阳性表达率分别为69.51%(57/82)和65.85%(54/82),明显高于癌旁组织14.63%(12/82)、12.20%(10/82)和正常组织9.76%(8/82)、7.32%(6/82)(P0.05);胃癌组织HMGA2、HDAC6蛋白和mRNA表达较癌旁组织及正常组织高(P0.05),且两者表达水平与肿瘤的临床分期和淋巴结转移相关(P0.05);HMGA2和HDAC6在胃癌组织中的表达呈明显正相关(r=0.56,P0.05)。结论 HMGA2和HDAC6基因在胃癌组织中存在高表达且共存现象,可能与胃癌恶性程度有关。     

HMGA1 proteins in human atherosclerotic plaques

One of the major characteristics of atherosclerosis is the migration of smooth muscle cells (SMC) from the tunica media to the intima, caused by alterations in the environment, e.g. mechanical, chemical, or immunologic injuries of the arterial walls. A group of molecules that may act as a main regulator of SMC phenotype switching is formed by the so-called HMGA1 high-mobility group proteins. One target gene of the HMGA1 protein, playing a major role in the development of atherosclerotic lesions, is CD44. The expression of CD44 is regulated by IL-1beta, but binding of HMGA1 potentiates the transactivation of the CD44 promoter. In this study, the HMGA1 expression of human atherosclerotic plaque samples was examined. Compared to the non-active components, all major components of the well-developed atherosclerotic plaques showed strong positivity of the high-mobility group protein HMGA1 in their activated areas, e.g. neointimal SMCs, macrophages, newly built blood vessels. This report is the first to describe HMGA1 as one of the first mediators in the development of human atherosclerotic plaques.