Composite mucinous and granulosa cell tumor of the ovary

A composite mucinous and granulosa cell tumor of the ovary in a 76-year-old woman is herein reported. At laparotomy this tumor proved to be a solid and cystic mass measuring 10 cm in greatest diameter. Many of the cysts were lined with a benign mucinous epithelium of the endocervical type, and solid areas contained a proliferation of granulosa cells. These two disparate components were intimately mixed. A theca cell component was also present in areas adjacent to the mucinous epithelium. The coexistence of mucinous and granulosa cell tumor is extremely rare and only four such cases have previously been reported in the literature, and the histogenesis of this tumor has not yet been elucidated. In the present case it is suggested that the granulosa cell element commenced as a reactive stromal hyperplasia in the wall of the pre-existing mucinous neoplasm and thereafter progressed to the point of producing a tumor-like mass or neoplastic changes.     

缝隙连接蛋白43和黄体生成素受体在小鼠卵巢中的表达

目的 观察小鼠卵泡发育过程中缝隙连接蛋白43（Cx43）和黄体生成素受体（LHR）在小鼠卵巢中的表达以及黄体生成素(LH)对卵巢Cx43表达的影响,为这两种分子与卵泡发育的关系提供实验依据。 方法 选择出生后1d、4d、7d、2周、3周、4周、6周、8周龄雌性C57小鼠共8组,每组10只,取卵巢。HE染色观察卵巢形态、卵泡发育并测量颗粒细胞体积分数。免疫组织化学和Western blotting观察卵巢组织中Cx43及LHR的表达,Western blotting检测不同浓度黄体生成素（LH）孵育后对卵巢Cx43表达的影响。 结果 HE染色显示,出生1d小鼠卵巢中见原始卵泡,出生7d卵巢内出现初级卵泡,2周时出现窦前卵泡和少量窦卵泡,3周、4周时,出现较多大的窦卵泡,6～8周时出现黄体。卵泡颗粒细胞体积分数在2周后的卵巢中明显增加。Cx43表达在各阶段卵泡的颗粒细胞胞膜上,LHR表达在卵泡膜细胞、颗粒细胞及卵母细胞胞质中。Cx43和LHR出生后2周卵巢中的表达开始明显增加,并随卵泡发育表达逐渐增强,在3周、4周、6周和8周维持相对较高水平。LH体外干预可增加卵巢组织Cx43的表达。 结论 Cx43和LHR在卵泡发育中发挥重要作用,LH可能通过LHR促进卵巢卵泡颗粒细胞Cx43的表达。     

Serous papillary adenocarcinoma and adult granulosa cell tumor in the same ovary. An unusual case

Surface epithelial-stromal cell tumors are the most common neoplasms of the ovary but occurrence of a serous adenocarcinoma and an adult granulosa cell tumor in the same ovary is an unusual incident. In the present case report we describe this very uncommon occurrence in the ovary of a 50-year-old woman. The patient suffered abdominal distention and was referred to the state hospital where a 5x3 cm multilocular cystic lesion was observed on abdominal CT. Total abdominal hysterectomy with salpingo-oophorectomy and omentectomy was performed. Microscopy revealed an adult granulosa cell tumor and a serous papillary adenocarcinoma in the left ovary. Immunohistochemical staining with inhibin alpha and pancytokeratin confirmed the diagnosis.     

Sex cord-stromal tumors of the testis

Testicular tumors apart from those in the germ cell family are uncommon and are mostly sex cord-stromal tumors and may pose a major diagnostic challenge. This review focuses on the clinicopathologic features of these uncommon neoplasms, pertinent differential diagnoses, relevant immunohistochemical and molecular findings as well as the recent updates proposed by the World Health Organization (WHO). Contrast between these neoplasms as seen in the male and female gonad will also be made when warranted. The commonest sex cord-stromal tumor of the testis is the Leydig cell tumor which, when seen in children, is often associated with sexual precocity. The histologic features are generally those of an easily recognized oxyphilic neoplasm but various peculiarities such as microcysts and spindling of the tumor cells may case diagnostic difficulty on occasion. In the male, in contrast to the female, the most common sex cord-stromal tumor of epithelial nature is the Sertoli cell tumor. Most of these fall in the not otherwise specified category and are usually characterized by a diagnostically helpful at least focal hollow or solid tubular pattern. Occasional malignant Sertoli cell tumors have a predominantly diffuse pattern sometimes interrupted by septa with a lymphocytic infiltrate that can cause seminoma to be mimicked. Rare Sertoli cell tumors are associated with marked sclerosis. The so-called large cell calcifying Sertoli cell tumor, may be sporadic or associated with manifestations of the Carney syndrome. A distinctive entity referred to as intratubular hyalinizing Sertoli cell neoplasia occurs in the testis of young boys with Peutz-Jeghers syndrome. It is often bilateral, microscopic and associated with gynecomastia. Testicular granulosa cell tumors are much rarer than their ovarian counterparts but can be similarly subdivided into adult and juvenile forms. In the male, the juvenile granulosa cell tumor has a particularly striking tendency to occur in the first 6 months of life. The primitive appearance of the nuclei and brisk mitotic activity of the juvenile granulosa cell tumor may result in a misdiagnosis of a more malignant neoplasm. The histologic spectrum of the adult granulosa cell tumor is as seen in the more common female examples. Pure stromal tumors of the testis are much less common than similar tumors in the ovary and the well-known thecoma is remarkably rare in the testis. Fibromas of stromal derivation in the testis should be distinguished from fibromas that originate from the tunica albuginea and from examples of the non-neoplastic process nodular pseudotumor.     

Normal human ovary and ovarian tumors express glycodelin, a glycoprotein with immunosuppressive and contraceptive properties.

Glycodelin is a glycoprotein with potent immunosuppressive and contraceptive activities. It reacts with antibodies against placental protein 14, or progesterone-associated endometrial protein, and has a unique carbohydrate structure. Previous nomenclature is misleading, because glycodelin is neither synthesized in the placenta nor is it endometrium specific. No ovarian synthesis of glycodelin has been demonstrated. We present evidence for glycodelin synthesis in the human ovary and ovarian tumors. In follicular phase, immunoperoxidase staining of microwave-treated tissue sections employing affinity-purified polyclonal antibodies localized glycodelin to areas of stromal cell condensation in ovarian cortex, theca interna, and the granulosa. In luteal phase, cortical stroma was negative or only weakly positive, whereas glycodelin was present in theca interna of the corpus luteum and luteinized granulosa cells and also in corpus albicans and Leydig cells of the ovarian hilus. In situ hybridization gave negative results for glycodelin mRNA in normal ovary, whereas in ovarian tumors strong expression of both the glycodelin mRNA and the protein were found in benign and malignant serous cystadenomas, mucinous ovarian tumors being negative. We conclude that glycodelin is synthesized in human ovarian tumors, and its occurrence in normal human ovary may represent either synthesis or a site of glycodelin action.     

Juvenile Granulosa Cell Tumor in a Three-year-old Infant An Immunohistochemical and Ultrastructural Study

A three-year-old female infant with a juvenile granulosa cell tumor of the ovary and precocious pseudopuberty is presented. Laboratory tests revealed elevated levels of serum and urinary estrogen. Histological examinations showed an immature follicular pattern surrounded by theca-like stromal tissue. The immunohistochemical localization of estradiol, estriol, progesterone and testosterone was studied by indirect immunoperoxidase staining of cryostat sections. All of these steroid hormones were localized mainly in stromal cells and in some follicular cells. Electron microscopic examination revealed three types of tumor cell, i.e. polygonal cells, spindle cells and transitional cells. Well developed smooth endoplasmic reticulum, mitochondria with tubulovesicular cristae, and lipid droplets in the cytoplasm, which are typical features of steroid synthesis, were conspicuous mainly in the last type of cell. Such transitional cells almost corresponded to steroid-positive cells. These cells were considered to have a close relationship to theca gland cells of developed ovarian follicles and to have mainly participated in steroid synthesis in the present tumor. In addition, some spindle cells showed features of myofibroblasts, such as intracyto-plasmic filaments, dense body-like structures, and pinocytotic vesicles. These features suggest that the cells might all be derived from the same progenitor of ovarian mesenchyme.     

围着床期小鼠卵巢黄体生成素受体和血管内皮生长因子表达的免疫组织化学研究

目的 探讨黄体生成素受体(LHR)和血管内皮生长因子(VEGF)在围着床期小鼠卵巢中的生物学作用. 方法 应用免疫组织化学SABC法和图像分析,检测LHR与VEGF在昆明小鼠( n =28)动情期、孕1d、孕4d和孕6d卵巢中的分布状况和变化规律. 结果 LHR与VEGF免疫阳性细胞具有相似的分布和变化规律.在动情期,较大的卵泡周围的基质细胞呈强阳性着色,与其他组相比,差异显著( P <0.05).随着妊娠的继续,颗粒黄体细胞的着色逐渐增强,在孕6d时表达最强.在动情期和孕1d,部分血管内皮和血细胞分别呈VEGF和LHR强阳性着色.从孕1d开始,卵泡膜细胞呈LHR阳性着色. 结论 LHR和VEGF的表达与围着床期小鼠卵巢中卵泡的发育、排卵和黄体形成过程密切相关.     

E-cadherin nuclear staining is useful for the diagnosis of ovarian adult granulosa cell tumor

We recently have demonstrated nuclear localization of E-cadherin in ovarian adult granulosa cell tumors (Histopathology 2011;58:423). The purpose of the present study is to investigate the diagnostic utility of E-cadherin nuclear staining for the differential diagnosis between ovarian adult granulosa cell tumor and its morphological mimics. Tissue samples taken from 81 ovarian tumors and 20 extraovarian tumors were immunohistochemically stained using monoclonal anti-E-cadherin antibody recognizing cytoplasmic domain (clone 36 supplied by BD Biosciences, San Jose, CA). The ovarian tumors consisted of 30 adult granulosa cell tumors, 3 Sertoli-stromal cell tumors, 14 fibrothecomas, 5 carcinoid tumors, 1 large cell neuroendocrine carcinoma, 18 endometrioid adenocarcinomas, and 10 poorly differentiated serous adenocarcinomas. Extraovarian tumors consisted of 16 uterine endometrial stromal neoplasms and 4 pulmonary small cell carcinomas. Only tumor cells with nuclear staining were considered positive in this study. Ninety percent of adult granulosa cell tumors, 67% of Sertoli-stromal cell tumors, 64% of fibrothecomas, 75% of endometrial stromal neoplasms, 75% of small cell carcinomas, and the one large cell neuroendocrine carcinoma showed E-cadherin nuclear expression, whereas all the ovarian carcinoid tumors, endometrioid adenocarcinomas, and poorly differentiated serous adenocarcinomas were negative. E-cadherin nuclear staining is useful in distinguishing between adult granulosa cell tumors and ovarian adenocarcinomas or carcinoid tumors. However, it is of limited use for distinguishing between adult granulosa cell tumors and endometrial stromal neoplasms or small cell carcinomas. E-cadherin should be included in the immunohistochemical panel for an accurate diagnosis of ovarian adult granulosa cell tumors.     

Localization of the progesterone receptor in the porcine ovary

Regulation of progesterone receptor (PR) expression has been studied in many species. However, precise studies have not yet been performed in the porcine ovary. We have examined the localization of PR in follicles and corpora lutea of the porcine ovary at different stages of their development. The effects of LH and FSH on PR expression in granulosa cells of small antral follicles was also studied. Immunohistochemistry was applied to determine the distribution of PR while immunoblot analysis showed that two isoforms A and B were present. Early antral follicles contained PR in the granulosa layer. In granulosa cells of small and medium antral follicles PR was not detected whereas it was present in the theca layer. Before ovulation, PR was found in both granulosa and theca cells of large follicles and the staining intensity was very strong. FSH or LH treatment of small follicles (100 ng/ml) induced changes in cellular distribution patterns of PR. In both cases, PR was expressed in granulosa cells. PR was detected in corpora lutea in all 3 stages of the luteal phase. Our data show that in the pig ovary changes in PR localization are stage-specific and suggest that expression of PR is positively regulated by both LH and FSH.     

Immunolocalization of Fas and Fas ligand in the ovaries of women with polycystic ovary syndrome: relationship to apoptosis

Both Fas (APO-1, CD95), an apoptosis-inducing receptor, and its ligand, Fas ligand (FasL, CD95L), have been localized to the ovary. Granulosa cell apoptosis occurs in antral follicular atresia. In polycystic ovary syndrome (PCOS), antral follicles accumulate with some atretic features. The ovarian expression of Fas and FasL was examined in PCOS by immunohistochemistry and correlated with immunodetection of apoptotic cells. Fas immunostaining was present in pre-antral follicle oocytes, some primary and secondary pre-antral follicle granulosa cells, and both granulosa and theca of antral follicles. Thecal staining persisted with advancing atresia, while granulosa staining declined. In antral follicles, abundant Fas-positive cells co-localized with scattered nuclei immunopositive for apoptosis. Ovarian vascular myocytes were strongly Fas-immunopositive. FasL immunostaining was present in pre-antral follicles in oocytes and variably in granulosa. In antral follicles, granulosa and thecal FasL staining increased with advancing atresia. Normal control ovaries showed follicular Fas and FasL staining patterns similar to those in PCOS, but vascular staining was less prominent. In one healthy follicle, Fas immunostaining was seen in the oocyte and weakly in mural granulosa and theca interna. The results suggest that in PCOS, an alteration in Fas-mediated apoptosis, does not cause abnormal folliculogenesis, but may promote ovarian vascular remodelling.     

Gynandroblastoma of ovary with juvenile granulosa cell component and heterologous intestinal type glands

An ovarian gynandroblastoma in a 15-year-old girl is described. The predominant component was juvenile granulosa cell tumour. Areas of adult granulosa cell tumour and Sertoli cell elements were also present. Stromal theca and luteinised cells were identified. An additional histological finding was the presence of heterologous intestinal type glands. There was positive immunohistochemical staining of juvenile and adult granulosa cell areas with inhibin and MIC2 antibodies. Electronmicroscopy showed a close ultrastructural resemblance between tumour cells in granulosa and Sertoli cell areas, in spite of differences in architectural pattern, suggesting that both morphological components may derive from a single cell of origin. The tumour demonstrates a unique combination of elements which has not previously been described.     

Kit ligand and c-Kit have diverse roles during mammalian oogenesis and folliculogenesis

Paracrine signalling between the oocyte and its surrounding somatic cells is fundamental to the processes of oogenesis and folliculogenesis in mammals. The study of animal models has revealed that the interaction of granulosa cell-derived kit ligand (KL) with oocyte and theca cell-derived c-Kit is important for multiple aspects of oocyte and follicle development, including the establishment of primordial germ cells within the ovary, primordial follicle activation, oocyte survival and growth, granulosa cell proliferation, theca cell recruitment and the maintenance of meiotic arrest. Though little is known about the specific roles of KL and c-Kit during human oogenesis, the expression profiles for KL and c-Kit within the human ovary suggest that they are also functionally relevant to female fertility. This review details our current understanding of the roles of KL and c-Kit within the mammalian ovary, with a particular focus on the functional diversity of this receptor-ligand interaction at different stages of oocyte and follicle development.     

Gonadotropin-releasing hormone receptor mRNA expression in the ovaries of neonatal and adult rats

Recent studies have shown that gonadotropin-releasing hormone (GnRH) can exert various effects on the rat ovary by acting through its specific receptors. To determine the cell types responsive to the action of GnRH under physiological conditions in the ovary, distribution of the GnRH receptor mRNA was studied histologically by in situ hybridization in neonatal and adult rats. Expression of the luteinizing hormone receptor mRNA was also examined to judge the growing state of follicles and the corpora lutea. In neonatal rat ovaries, no significant GnRH receptor mRNA signal was detected until 5 days after birth. The expression was first observed at 10 days in the interstitial cells. At 15 days of age, the receptor mRNA was expressed in the granulosa cells of most preantral and early antral follicles, while no hybridization signal was detected in oocyte and theca cells. In adult cycling rats, GnRH receptor mRNA was detected mainly in the granulosa cells of most follicles and luteal cells. The granulosa cells of atretic follicles showed a very high level of the mRNA expression throughout their degenerating process. A strong hybridization signal was also detected in the mural granulosa cells of mature follicles. Newly formed (developing) corpora lutea exhibited signals with moderate intensity in the luteal cells, and the older ones showed weaker signals. The finding that the initial expression of GnRH receptor mRNA was seen in the interstitial cells of neonatal ovaries implies an unknown function of the ovarian GnRH receptor in ovarian development. The high level expression of GnRH receptor mRNA in atretic and mature follicles supports the putative roles of GnRH in the induction of follicular atresia and ovulation in rat ovaries.     

卵巢幼年型粒层细胞瘤的临床病理分析

目的 分析卵巢幼年型粒层细胞瘤的临床病理特点,探讨其诊断标准、特殊形态及预后因素等.方法 对7例幼年型粒层细胞瘤的临床资料行回顾性分析总结、组织切片进行形态观察,对其中6例行免疫组织化学EliVision法染色.6例进行了随访.结果 7例幼年型粒层细胞瘤的平均年龄为24岁(6～53岁).5例有性激素紊乱的临床表现,2例以腹胀及腹痛为主要症状.除1例(例2)行全子宫和双附件切除,其余6例均为一侧附件切除.5例Ⅰ A期,2例Ⅰ C期.6例随访病例中除1例(例1)术后1年余死于肿瘤转移,其余5例健在,随访时间平均4.3年(1～10年).肿瘤最大径7～20 cm(平均13.4 cm),4例囊实性,2例单房囊性,1例实性.镜下全部为弥漫生长和不典型滤泡样结构,未见Call-Exner小体.肿瘤细胞核小、较圆、深染,极少见核沟,3例重度异形,1例中度,3例轻度.1例(例2)小灶有成年型粒层细胞瘤特征.5例核分裂象＞5/10 HPF,2例核分裂象不易见.6例CK(AE1/AE3)阴性、波形蛋白强阳性;1例α-抑制素阳性;4例CD99阳性、Calretinin阴性.结论 幼年型粒层细胞瘤以不典型滤泡样结构而非Call-Exner小体为结构特点,以核小、圆形、深染而无核沟为主要细胞学特点,以大多数CK阴性和波形蛋白阳性为特殊免疫表型,兼以有少量成年型粒层细胞肿瘤结构及单房囊性肿瘤为其特殊形态.肿瘤破裂可能是影响预后的一个重要因素,核异形、核分裂象多见及肿瘤体积大并不能提示肿瘤具有恶性潜能.     

Anti-Müllerian hormone is a specific marker of sertoli- and granulosa-cell origin in gonadal tumors

Sex cord stromal tumors are gonadal neoplasms containing Sertoli, granulosa, Leydig, or thecal cells, which originate from cells derived from either the sex cords (Sertoli and granulosa cell tumors) or the specific mesenchymal stroma (Leydig and thecal cell tumors) of the embryonic gonad. Only granulosa and Sertoli cells produce anti-Müllerian hormone (AMH). Our purpose was to investigate whether AMH can be used as a specific marker of human granulosa or Sertoli cell origin in gonadal tumors, to distinguish them from other primary or metastatic neoplasms, using immunohistochemistry. We studied 7 juvenile and 6 adult-type granulosa cell tumors of ovarian localization and 3 extraovarian metastases, 20 other ovarian tumors, 6 testicular Sertoli cell tumors, 2 gonadoblastomas, and 13 extragonadal tumors. Granulosa cell tumors, both juvenile- and adult-type of either ovarian or metastatic localization, showed an heterogeneous pattern of AMH immunoreactivity: Areas containing intensely or weakly AMH-positive cells were intermingled with AMH-negative areas. Although in most cases AMH-positive areas represented a minor proportion of tumor cells, we found a positive reaction in all the cases examined. In testes, although normal prepubertal Sertoli cells were intensely positive, testicular Sertoli cell tumors showed large areas of negative reaction, with few positive cells scattered throughout the tumor. AMH was also reactive in most of the cells of sex-cord origin in gonadoblastomas. No AMH immunoreaction was observed in other gonadal and extragonadal tumors. We conclude that AMH expression is conserved in only a small proportion of tumor cells of granulosa or Sertoli cell origin; however, a positive reaction in a few cells helps to distinguish between granulosa or Sertoli cell tumors or gonadoblastomas and other gonadal tumors of different origin.     

Immunohistochemical characterization of extracellular matrix components of granulosa cell tumor of ovary

In order to clarify the characteristics of granulosa cell tumors of the ovary, extracellular matrix components were investigated by immunohistochemical techniques. Twenty-three granulosa cell tumors (GCT; eight juvenile and 15 adult type) were studied in comparison with non-neoplastic granulosa cells of human ovaries. In all 23 cases of GCT, chondroitin 6-sulfate proteoglycan revealed with antibody 3B3 was characteristically observed in the extracellular matrix in the solid nest, as well as in microfollicles. In the juvenile cases, the extracellular matrix also contained large proteoglycan (PG) revealed with antibody 2B1. Macrofollicles as well as micro-follicles contained PG chondroitin 6-sulfate side chains with a significant amount of chondroitin 4-sulfate. By biochemical analysis using high pressure liquid chromatography, it was also found that disaccharide composition of glycosaminog-lycan fractions extracted from granulosa cell tumor tissues consisted mainly of 2-acetamide-2-deoxyl-3-0-(β-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (δ Di-6S). The characteristic feature of granulosa cell tumors is the accumulation of chondroitin sulfate PG, especially chondroitin 6-sulfate PG, which may be synthesized by the tumor cells themselves. Immunohistochemical characterization of the extracellular matrix components (collagen, laminin, heparan sulfate PG, chondroitin 4-sulfate PG) was also studied in relation to chondroitin 6-sulfate PG localization.     

Immunohistochemical localization of the LH/HCG receptor in human ovary: HCG enhances cell surface expression of LH/HCG receptor on luteinizing granulosa cells in vitro

We examined the immunohistochemical localization of luteinizing hormone (LH)/human chorionic gonadotrophin (HCG) receptor (LH-R) in the human ovary using the anti-human LH-R monoclonal antibody, 3B5. In the antral follicles, LH-R was detected on theca interna cells. In pre-ovulatory follicles, granulosa cells also expressed LH-R. During corpus luteum formation, granulosa cells seemed to increase the expression of LH-R, and in corpus luteum of mid-luteal phase, large luteal cells expressed LH-R more intensely than small luteal cells. In the regressing corpus luteum, LH-R was almost undetectable on both luteal cells, whereas in the corpus luteum of early pregnancy, LH-R continued to be expressed on large luteal cells. The granulosa cells obtained from the patients undergoing in-vitro fertilization therapy were cultured for 3 days in serum-free medium, without or with HCG (10 IU/ml) and tumour necrosis factor (TNF)alpha (10 ng/ml). Flow cytometry showed that the expression of LH-R on the cell surface of luteinizing granulosa cells was enhanced by HCG, but was unaffected by TNFalpha. These results suggest that the main target cells for LH/HCG change from theca interna cells/small luteal cells to granulosa cells/large luteal cells during ovulation, corpus luteum formation, and differentiation into the corpus luteum of pregnancy, probably under the influence of LH/HCG.      

Cytologic features of pulmonary metastasis from a granulosa cell tumor diagnosed by fine-needle aspiration: A case report

We report on a case of a granulosa cell tumor of the ovary metastatic to the lung and diagnosed by fine-needle aspiration. The patient was a 70-yr-old woman who was diagnosed with a granulosa cell tumor of the ovary 17 yr previously. She subsequently developed abdominal metastases and received several cycles of chemotherapy. A 0.5-cm right upper lobe pulmonary nodule was found on a routine chest radiograph and subsequent computerized tomography scan. Aspiration cytology of this pulmonary nodule demonstrated small, relatively uniform neoplastic cells with nuclear grooves and indentations consistent with a granulosa cell tumor. The differential diagnosis of granulosa cell tumors from other metastatic and pulmonary lesions is reviewed. Diagn. Cytopathol. 16:341–344, 1997. © 1997 Wiley-Liss, Inc.     

硫代bFGF寡核苷酸抑制HepG2和Hep2细胞的增殖

目的探讨硫代修饰对bFGF寡核苷酸抑制HepG2和Hep2细胞增殖的影响。方法设计、合成bFGF寡核苷酸,聚乙烯亚胺(jetPEI)介导其转染入HepG2和Hep2细胞,荧光显微镜观察其在细胞中的定位,流式细胞仪分析转染效率,MTT法检测细胞增殖。结果bFGF反/正义硫代寡核苷酸被jetPEI介导高效转染入细胞内,主要位于细胞核。反/正义硫代寡核苷酸均呈剂量时间依赖地抑制细胞增殖,相同剂量时正硫代寡核苷酸的抑制效率高于反义硫代寡核苷酸。相应非修饰反义寡核苷酸较其互补正义链能更有效抑制两种细胞增殖。核苷酸突变明显降低反义硫代寡核苷酸对细胞抑制,并不影响正义硫代寡核苷酸的细胞抑制率。反义硫代寡核苷酸明显降低细胞中bFGF表达。结论硫代修饰bFGF反义寡核苷酸在细胞内特异性结合核酸以反义机制抑制肿瘤细胞增殖,正义寡核苷酸则因硫代修饰于细胞内以非核酸特异性机制抑制肿瘤细胞增殖。     

Calretinin expression in human normal and neoplastic tissues: a tissue microarray analysis on 5233 tissue samples

Calretinin is a calcium-binding protein expressed in different normal and neoplastic tissues. Early studies suggested that calretinin is a useful marker to differentiate adenocarcinomas from malignant mesotheliomas of the lung, but subsequent work has shown that calretinin can be expressed in several other tumor types. To systematically investigate the epidemiology of calretinin expression in normal and neoplastic tissues, we used tissue microarrays (TMAs) to analyze the immunohistochemically detectable expression of calretinin in 5233 tissue samples from 128 different tumor categories and 76 different normal tissue types. At least 1 case with weak expression could be found in 74 of 128 (58%) different tumor types and 46 entities (36%) had at least 1 tumor with strong positivity. In normal tissues, a particularly strong expression was found in Leydig cells of the testis, neurons of the brain, theca-lutein and theca interna cells of the ovary, and mesothelium. In tumors, strong calretinin expression was most frequently found in malignant mesotheliomas (6 of 7), Leydig cell tumors of the testis (5 of 5), adenomas of adrenal gland (5 of 9), and adenomatoid tumors (4 of 9). In summary, calretinin is frequently expressed in many different tumor types. Metastases of various different origins must be included in the differential diagnosis of calretinin-positive pleura tumors.