Malignant Rhabdoid Tumor of the Breast: A Case Report

A 66-year-old woman time of 10 days. One month after radicalmastectomy, there was local recurrence, followed by multiplepulmonary metastases, and the patient died of respiratory failure5 months after surgery. The gray-white-colored tumor measured13x12x;10 cm, and its border was well defined. The tumor wascomposed of diffusely growing round or polygonal cells withvesicular nuclei, prominent nucleoli, and ample cytoplasm containingeosinophilic inclusions. Lymph node involvement was widespread.Both vimentin and keratin were clearly demonstrated by immunohistochemicalstaining. Ultrastructural studies revealed that the MRT cellscontained cytoplasmic whorls of intermediate filaments.     

肿瘤细胞染色质雌激素受体检测

采用E_2-HRP方法检测人肝细胞癌、胃癌、人胚肝、脑和脾组织的细胞染色质中雌激素受体(ER)并定位,发现这两种癌细胞染色质中都存在ER,但在上列入胚组织中均未测出。这一初步结果如能得到进一步阐明,将有助于了解ER在肿瘤发生与发展过程中作用的分子生物学机理。     

The Autocrine Loop of Epidermal Growth Factor Receptor-Epidermal Growth Factor/Transforming Growth Factor-α in Malignant Rhabdoid Tumor Cell Lines: Heterogeneity of Autocrine Mechanism in TTC549

To investigate the effects of the autocrine loop of epidermal growth factor receptor (EGFR)-epidermal growth factor (EGF)/transforming growth factor-α (TGF-α) on the proliferation and differentiation of malignant rhabdoid tumor (MRT), we used five MRT cell lines, TM87-16, STM91-01, TTC549, TTC642, and YAM-RTK1. RT-PCR analyses revealed expression of EGFR mRNA in all MRT cell lines. In contrast, the expression of either EGF or TGF-α mRNA was detected in all MRT cell lines. Expression of EGF, TGF-α, and EGFR as determined by immunocytochemical staining and in situ hybridization, correlated with the results of RT-PCR. Upon differentiation-induction with 12-O-tetradecanoylphorbol-13-acetate (TPA), in TTC549, showing an expression of TGF-α but not EGF initially, de novo expression of EGF mRNA appeared abruptly on day 2 of TPA treatment. To confirm the EGFR-EGF/TGF-α autocrine loop, we used TGF-α, EGF, and their antibodies in the cultures. Monoclonal antibody (mAb) to EGFR alone significantly inhibited the growth of cell line TTC549. However, mAb to EGF or TGF-α could inhibit proliferation of this cell line only when administrated together. Our findings would suggest that growth of the TTC549 cell line is constitutionally regulated by TGF-α/EGFR, but that inhibition of this autocrine mechanism results in transient activation of an autocrine loop involving EGF/EGFR. Our results may indicate the presence of two different autocrine loops of EGFR-EGF and/or EGFR-TGF-α in MRT cell lines. The heterogeneity of autocrine mechanisms found in MRT cell lines would be consistent with the multiphenotypic diversity and aggressive characteristics of this enigmatic tumor.     

人体正常卵巢和卵巢恶性肿瘤雌激素及孕激素受体5年研究总结

用葡聚糖—活性炭单点饱和分析法测定261例正常卵巢组织,148例卵巢恶性肿瘤组织胞浆雌激素受体和孕激素受体(ER.PR)。结果表明,正常卵巢组织ER和PR均值和阳性率均高于恶性卵巢肿瘤组织。卵巢恶性病变中,性腺间质类ER和PR含量均高于上皮性肿瘤.生殖细胞源性肿瘤和转移性癌。上皮性恶性肿瘤中,内膜样癌的ER和PR含量高于浆液性,粘液性及透明细胞癌。提示受体含量高者有用内分泌治疗的可能和推测有转好的预后。卵巢恶性肿瘤患者临床分期及月经状况与其ER阳性率有关,而与PR阳性率无关。     

Malignant Rhabdoid Tumor in a Pregnant Adult Female: Literature Review of Central Nervous System Rhabdoid Tumors

Summary Rhabdoid tumors of the central nervous system are uncommon, aggressive childhood malignancies. The 13 described adult cases comprise both primary CNS tumors and malignant transformation of previously existing gliomas, meningiomas, and astrocytomas. Central nervous system rhabdoid lesions of adults have been diagnosed as primary malignant rhabdoid tumors, atypical teratoid/rhabdoid tumors, and more recently, rhabdoid glioblastomas. We report a case of a 20-year-old woman in her 30th week of pregnancy who presented with headache, nausea and blurry vision. MRI revealed a large rim-enhancing mass of the right occipital lobe. Gross total resection was achieved via a right parietal-occipital craniotomy. Pathologic evaluation revealed histology, electron microscopy and immunohistochemistry consistent with the diagnosis of malignant rhabdoid tumor. FISH studies were negative for the INI-1 genetic mutations and chromosome 22q deletion associated with childhood atypical rhabdoid/rhabdoid tumor in 75% of cases. The patient delivered her infant via caesarian section prior to initiating further therapy. We briefly describe the characteristics and current understanding of rhabdoid tumors, and review the literature comparing the 12 other cases of central nervous system rhabdoid tumors in adults. Furthermore, we consider and discuss the implications of this case being the second presentation of MRT during pregnancy in only six adult female patients.     

Estrogen Receptor Levels and Tumor Growth in a Series of Pituitary Clonal Cell Lines in Rats

Four kinds of in vitro clonal pituitary tumor cell lines named MtT/Se, MtT/SM, MtT/S and MtT/ E, each of which shows different sensitivity to estrogen on proliferation, were inoculated into fat pad of ovariectomized rats and estrogen-loaded ovariectomized rats at 10⁵ and 10⁶ cells/site. They formed tumor with average latency ranging from 30 to 71 in ovariectomized rats and 13 to 63 days in estrogenized rats inoculated with 106 cells. MtT/Se was highly sensitive to estrogen for growth, and MtT/SM also grew well in estrogenized rats. With MtT/S and MtT/E, there was no significant shortening of average tumor latency in estrogenized rats. In vivo , the cytosolic estrogen receptor (ER) levels of MtT/Se, SM, S and E were measured to be 452 ±66, 370 ±115, 260 ±16 and 83 ±8 fmol/ mg protein, respectively. In vitro , however, the lowest ER level was noted in MtT/Se. Histologically, all four tumors grown in rats were composed of homogeneous round cells, and MtT/Se contained particularly large nucleated cells. In MtT/E, the cells appeared to be changing into ftbromatous cells. Three cell lines except MtT/E maintained the function of hormonal secretion in vivo as well as in vitro . Serum GH level was increased in rats with MtT/Se and MtT/S. Increased levels of both prolactin and growth hormone were measured in sera of rats with MtT/SM. Increases of hormones as well as tumor sizes were promoted by the estrogen.     

Binding Sites of Droloxifene in the Cytosol of 7,12-Dimethylbenz[α]anthracene-induced Rat Mammary Tumor Cells

The binding sites, other than the estrogen receptor (ER), of the antiestrogens droloxifene (DROL, (E)-α-[ p [2-(dimethylamino)ethoxy]-phenyl]-α'-ethyl-3-stilbenol) and tamoxifen (TAM), and estradiol-17β (E₂) in the cytosol of 7,12-dimethylbenz[α]anthracene-induced rat mammary ER-positive tumor cells were studied using a high-performance liquid chromatography (HPLC) gel filtration assay. The cytosol was incubated with ³H-labeled drug with or without unlabeled drug, and separated by HPLC gel filtration. ³H-E₂ produced two major peaks of radioactivity at fractions No. 40 and No. 70. The peak at fraction No. 70 was identified as the ER in an ER-enzyme-immuno assay. This peak was dose-dependently inhibited by unlabeled DROL or TAM, DROL being a more potent inhibitor than TAM. The peak at fraction No. 40 was also inhibited by co-incubation with unlabeled DROL or TAM. ³H-DROL or ³H-TAM provided only one peak at fraction No. 43. This peak was thought to be an antiestrogen binding site (AEBS), because it was inhibited by unlabeled antiestrogen hut not by E₂. The results suggest that the antiestrogens DROL and TAM have a higher affinity for the AEBS than for the ER in the absence of E₂, while in the presence of E₂ both have an affinity for the ER and inhibit E₂ binding to the ER.     

卵巢恶性肿瘤雌激素受体及孕激素受体的研究

应用酶联雌二醇（Ｅ２－ＨＲＰ）和酶联孕酮（Ｐｇ－ＨＲＰ）亲和组化法检测卵巢恶性肿瘤雌激素受体和孕激素受体４５例，结果ＥＲ阳性３５例，ＰｇＲ阳性３３例，其阳性检出率依次为７７％和７３％，不同类型肿瘤的受体水平有差异，上皮性癌肿的阳性检出率较转移癌高。检测结果显示：肿瘤分化越好，受体水平也越高，早期癌比晚期癌的ＥＲ，ＰｇＲ受体水平高，受体阳性者术后加用他莫西芬联合化疗治疗，其生存时间较阴性者长，复发亦     

Estrogen Receptor Mutations and Changes in Estrogen Receptor and Progesterone Receptor Protein Expression in Metastatic or Recurrent Breast Cancer

To investigate the frequency of estrogen receptor ( ER ) gene mutation in metastatic or recurrent breast cancer, metastatic lymph nodes or recurrent breast cancer tissue from 35 patients with ER-positive primary tumors were screened for mutations in the hormone-binding domain of the ER gene by sequence analysis. Four missense mutations, Val316Ile, Gly344Val, Ala430Val and Gly494Val, were identified in these lesions. Second, to clarify whether there is any disparity in hormone receptor status between primary and metastatic or recurrent tumors, we immunohistochemically studied 117 specimens including the above 35 specimens obtained from metastatic or recurrent breast cancer patients using monoclonal anti-ER and progesterone receptor (PgR) antibodies. Although hormone receptor status, especially ER, was highly maintained through disease progression, negative change in PgR expression at relapse (33%) was identified more frequently than in metastatic lymph nodes (6.7%). Therefore, it was suggested that development of PgR-negative phenotype might correlate with disease progression in some breast cancer patients. These results suggest that ER mutations in metastatic or recurrent breast cancer may be more frequent than in primary lesions, irrespective of high maintenance of ER protein expression through disease progression.     

瘦素、雌激素及雌激素受体在肺癌组织中的表达及其相关性

目的 探讨瘦素、雌激素及雌激素受体在肺腺癌及肺鳞癌组织中的表达及其意义.方法 对41例肺腺癌和32例肺鳞癌组织及标本行免疫组织化学染色,检测瘦素、雌激素和雌激素受体的表达,并比较瘦素、雌激素及雌激素受体在肺腺癌及肺鳞癌组织中表达的差异,探讨其与肺腺癌之间的关系.结果 41例肺腺癌中瘦素、雌激素及雌激素受体阳性例数分别为32例(78.05％)、15例(36.59％)及25例(60.98％);32例肺鳞癌中瘦素、雌激素及雌激素受体阳性例数分别为18例(56.25％)、5例(15.63％)及12例(37.5％),差异均有统计学意义(P＜0.005).27例女性肺腺癌中,ER阳性例数为20例(74.07％);14例男性肺腺癌中,ER阳性例数为5例(35.71％),差异有统计学意义(P＜0.05).肺腺癌中瘦素、雌激素表达在性别、肺癌类型和临床分期间差异无统计学意义(P＞0.05).结论 瘦素、雌激素及雌激素受体在肺腺癌组织中均呈高表达,女性肺腺癌中ER呈高表达,与肺腺癌的发生、发展和临床类型可能存在一定相关性.     

恶性肿瘤患者外周血细胞凋亡检测的意义

为了探讨恶性肿瘤患者外周血细胞的生物学特性变化的临床意义，作者用流式细胞术对８４例恶性肿瘤患者血细胞凋亡水平进行了检测分析。结果表明，肿瘤患者细胞凋亡水平显著高于健康人（分别为５．５１％±８．５２％和０．２５％±０．２８％，Ｐ＜０．０１）；患者细胞凋亡水平虽然随Ｓ期细胞增高有逐渐减低的趋势，但无明显的线性关系。ＤＮＡ异倍体患者凋亡水平虽然低于二倍体患者，但无统计学意义（Ｐ＞０．０５）。这表明，恶性肿瘤患者外周血细胞凋亡水平变化不仅代表恶性肿瘤一种生物学特性，而且还可以作为恶性肿瘤诊断的良好指标。最后对患者外周血细胞中出现凋亡的原因作了分析。     

卵巢恶性肿瘤雌,孕激素受体状态及其与临床,病理关系的初步探讨

用ＤＣＣ方法检测了５５例卵巢恶性肿瘤及１２例良性肿瘤胞浆雌激素受体（ＥＲ），其中３４例还同时测定了孕激素受体（ＰｇＲ）。结果表明，卵巢恶性肿瘤中４１．８％ＥＲ阳性，４１．２％ＰｇＲ阳性，明显高于良性肿瘤，后者ＥＲ为８．３％，ＰｇＲ为２０．０％。卵巢恶性肿瘤中的ＥＲ、ＰｇＲ与某些临床、病理因素有一定关系。性索间质肿瘤的ＥＲ含量最高（１２６．６ｆｍｏｌｅ／ｍｇ），生殖细胞瘤最低（５．３ｆｍｏｌｅ／ｍｇ）。ＰｇＲ则在性索间质肿瘤及上皮性病中较高（分别为４９．８ｆｍｏｌｅ／ｍｇ及４８．６ｆｍｏｌｅ／ｍｇ）。ＥＲ有随肿瘤组织学分级增高而下降的趋势，ＰｇＲ则无明显规律。两种受体在临床早期组均高于晚期组。经过长期随访发现，ＥＲ、ＰｇＲ阳性患者的５年存活率及平均生存时间均比阴性患者高。本研究初步表明，卵巢恶性肿瘤中亦有部分为性激素依赖性肿瘤，且受体的状态与肿瘤的分化程度及患者的预后有一定关系，这就为卵巢癌的内分泌治疗及对预后的估价奠定了一定的理论基础。     

The Neurokinin-1 Receptor Is a Target in Pediatric Rhabdoid Tumors

Rhabdoid tumors (RT) are among the most aggressive tumors in early childhood. Overall survival remains poor, and treatment only effectively occurs at the cost of high toxicity and late adverse effects. It has been reported that the neurokinin-1 receptor/ substance P complex plays an important role in cancer and proved to be a promising target. However, its role in RT has not yet been described. This study aims to determine whether the neurokinin-1 receptor is expressed in RT and whether neurokinin-1 receptor (NK1R) antagonists can serve as a novel therapeutic approach in treating RTs. By in silico analysis using the cBio Cancer Genomics Portal we found that RTs highly express neurokinin-1 receptor. We confirmed these results by RT-PCR in both tumor cell lines and in human tissue samples of various affected organs. We demonstrated a growth inhibitory and apoptotic effect of aprepitant in viability assays and flow cytometry. Furthermore, this effect proved to remain when used in combination with the cytostatic cisplatin. Western blot analysis showed an upregulation of apoptotic signaling pathways in rhabdoid tumors when treated with aprepitant. Overall, our findings suggest that NK1R may be a promising target for the treatment of RT in combination with other anti-cancer therapies and can be targeted with the NK1R antagonist aprepitant.     

大肠癌雌激素受体和P—糖蛋白表达的研究

为了研究大肠癌雌激素受体（ＥＲ）与Ｐ糖蛋白（Ｐｇｐ）表达之间的关系,采用免疫组化法检测６５例大肠癌组织及２１例正常大肠粘膜的ＥＲ及Ｐｇｐ表达情况。大肠癌组织ＥＲ与Ｐｇｐ的表达率分别为７５．４％、７３．８％。ＥＲ及Ｐｇｐ的表达率在大肠组织明显高于相邻正常粘模（Ｐ＜０．０５,Ｐ＜０．０１）,不论是大肠癌组织还是正常大肠粘膜,其ＥＲ与Ｐｇｐ的表达无相关性（Ｐ＞０．０５）,ＥＲ及Ｐｇｐ表达与患者性别、年龄、肿瘤大小、形态、部位及Ｄｕｋｅｓ′分期均无显著相关。研究表明大肠粘膜在癌变过程中ＥＲ和Ｐｇｐ的表达增加;ＥＲ、Ｐｇｐ作为单一指标尚难判断大肠癌病情及预后。     

乳腺肿瘤雌、孕激素受体表达与细胞增殖

目的：观察乳腺肿瘤雌、孕激素受体表达与细胞增殖的关系。方法：用免疫细胞化学技术（ＡＢＣ法）对经病理确诊２５５例恶性和６６０例良性乳腺肿瘤进行了ＥＲ、ＰＲ、ｃ－ｅｒｂＢ－２、ｐ５３基因蛋白表达和Ｋｉ－６７抗原检测。结果：良、恶性乳腺肿瘤间,ＥＲ、ＰＲ阳性率均有极显著差异。良性肿瘤组中,ＥＲ＋ＰＲ＋组和ＥＲ－ＰＲ－组间差异有显著性;ｐ５３表达率在ＥＲ、ＰＲ阴、阳性组间差异有显著性;ｃ－ｅｒｂＢ－２表达     

恶性肿瘤患者化疗前后外周血淋巴细胞凋亡的变化

为了探讨肿瘤化疗机理，作者采用流式细胞术单参数分析方法，检测了４５例恶性肿瘤患者化疗前后外周血细胞的凋亡（Ａｐｏ）、Ｓ期细胞比率（ＳＰＦ）和增殖指数（ＰＩ）的变化。结果表明，肿瘤患者血细胞Ａｐｏ水平明显高于正常对照（Ｐ＜０．０１），化疗结束时进一步升高（Ｐ＜０．０１），化疗后１个月又恢复到化疗前的水平。肿瘤患者的ＳＰＦ和ＰＩ均显著高于正常对照（Ｐ＜０．０１），化疗结束时明显减低，ＰＩ尤为显著（Ｐ＜０．０１），并持续到化疗后１个月。从而可见，化疗使患者血细胞Ａｐｏ呈“一过性”增高，肿瘤的化疗机制主要是化疗药物使细胞增殖活性减低，细胞聚积在Ｇｏ／Ｇ１期，同时药物诱导细胞凋亡增加，达到治疗肿瘤的目的     

Expression of Estrogen Receptor Alpha and Beta in Breast Cancers of Pre- and Post-menopausal Women

Expression of estrogen receptors (ER) is clinically relevant in designing therapeutic strategies. The relative importance of the two types of estrogen receptors (ER-alpha and ER-beta) in human breast cancers in pre- and post-menopausal women has not been properly defined. To determine the possible association between the expression of estrogen receptor and serum estradiol levels in pre- and post-menopausal women with breast cancer. 44 patients with invasive ductal carcinoma of the breast were studied and a breast tissue biopsy was taken. ER-alpha and ER-beta were detected by immunocytochemistry. Serum levels of estradiol and estrone were measured by radioimmunoassay and FSH was measured using IRMA. We studied 21 pre- and 23 post-menopausal women with breast carcinoma. Examining the number of cases with tumors positive for ER, we found no differences in the frequency of ER-alpha between pre- and post-menopausal women, but ER-beta decreased marginally after menopause (p < 0.051). In cases with tumors positive for ER, the proportion of cells positive for ER-alpha was similar post-menopausally (53.95%) and pre-menopausally (57.21%), but for ER-beta the number of positive cells decreased significantly after menopause (p < 0.051). In pre-menopausal women there was a correlation between serum estradiol levels and ER-beta; in post-menopausal women there was a correlation between serum FSH levels and ER-alpha. These results indicate that estradiol levels in women with mammary carcinoma are related to ER-beta expression in the breast tumor tissue.