Immunohistochemical and histochemical markers of primary lung cancer, lung metastases, and pleural mesotheliomas

Sections of primary lung carcinomas, lung metastases, mesotheliomas, and lung metastases of some rare mesenchymal tumors were incubated with different cytokeratin (CK), vimentin, desmin, and tissue polypeptide antigen (TPA) antibodies and with antibodies reactive with different hormones (ACTH, PTH, alpha-HCG, Calcitonin CT), CEA, carcinoma-associated antigen (CA1), secretory component (SC), neuron-specific enolase (NSE), alpha-1-antitrypsin (alpha-1-AT), lysozyme (lyso), and S-100 protein (S 100). CK antibodies derived from a 49 kD (reactive with simple epithelia [SE]) and a 67 kD CK polypeptide fraction (reaction with complex epithelia [CE] were useful differentiation markers for the four major groups of lung carcinomas. In one half of small cell carcinomas a positive reaction with NSE antibodies was found. S 100 and SC were good markers for papillary and bronchioloalveolar adenocarcinomas, whereas CEA was less important because of its reactivity with different types of lung carcinomas. To discern clear cell carcinomas of lung and renal origin a positive reaction with vimentin antibodies (some renal but not lung types) and with CA1 (no renal but all lung types) seemed to be useful. All hormone antibodies were of no importance as markers for difficult differential diagnosis, because positive reactivities were found in cases from every major carcinoma group. In addition, a Ca2+-activated adenosine triphosphatase (ATPase) was found in mesotheliomas but not in papillary adenocarcinomas.     

CK在恶性黑色素瘤中的表达

 目的 检测CK在恶性黑色素瘤中的表达情况及意义。方法 应用免疫组化PV-9000二步法对18例恶性黑色素瘤进行CK、Vimentin、S-100、HMB45的检测。结果 在18例恶黑中CK的阳性表达率为67％(12／18)；其中原发性恶黑16例，CK和Vimentin的表达率分别为63％(10／16)、100％(16／16)；CPK与S-100，CK与HMB45两项均呈阳性表达者各占50％(8／16)，以上四项抗体均为阳性的表达率为44％(7／16)；两例转移性恶黑四项抗体均为阳性表达，占100％(2／2)。结论 CK在原发性和转移性恶黑中均有不同程度的阳性表达。     

Sarcomatoid carcinoma of the urinary bladder: a case report with immunohistochemical and molecular genetic analysis

The author reports a rare case of sarcomatoid carcinoma with an emphasis on immunohistochemical features. A 79-year-old man was admitted to our hospital because of hematuria. An endoscopy revealed a large polypoid tumor in the bladder, and urine cytology demonstrated malignant cells. A cystectomy was performed. The patient is now alive without metastasis 4 months after the operation. Grossly, a large polypoid tumor (5 × 6 × 5 cm) was present in the bladder. Microscopically, the tumor consisted of high-grade transitional cell carcinoma element (10% in area) and sarcomatoid element (90% in area). There was a gradual transition between the two. The tumor cells were invaded into peribladder tissue (pT3b). Immunohistochemically, the sarcomatoid element was positive for four types of pancytokeratins, high-molecular weight cytokeratin (CK), CK5/6, CK7, CK18, CK19, epithelial membrane antigen (EMA), vimentin, p53 protein, p63, Ki-67 (labeling = 92%), neuron-specific enolase (NSE), and platelet-derived growth factor receptor-α (PDGFRA). It was negative for CK14, CK20, melanosome, carcinoembryonic antigen (CEA), desmin, S100 protein, myoglobin, α-smooth muscle antigen (ASMA), CD34, chromogranin, synaptophysin, CD56, CD68, and KIT. The transitional cell carcinoma element showed similar immunoreactivity except for negative CK5/6, positive CK20, and negative vimentin. A molecular genetic analysis of KIT gene (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) gene with the use of PCR-direct sequencing showed no mutations. The present case is the first report of sarcomatoid carcinoma of the urinary bladder demonstrating extensive immunohistochemistry and mutational status of KIT and PDGFRA genes. The sarcomatoid carcinoma in the present case may be derived from sarcomatous differentiation of high-grade transitional cell carcinoma.     

Tumor markers in human renal cell carcinoma

Localization of tumor markers in human renal cell carcinomas (RCC) was studied by an immunohistochemical method using 12 different monoclonal antibodies (MAbs) recognizing carbohydrate antigens, and 2 polyclonal antibodies against S-100 protein and neuron-specific enolase (NSE), respectively. 115D8, DF3 and the MAb to epithelial membrane antigen (EMA) reacted with 9 of 13 (115D8), 6 of 13 (DF3) and 5 of 12 (MAb to EMA) cases of RCC, respectively. S-100 protein was also found in 10 of 13 cases of RCC. Further immunohistochemical studies showed that tumor cells of all 13 RCCs were strongly positive for NSE. Serum NSE levels of patients with RCC were examined by radioimmunoassay. This examination revealed that increased levels of NSE were detected in 11 of 17 sera of patients with RCC. Positive rates for patients in stages II, III and IV were 100% (10/10). On the other hand, increased levels of CA15-3 were detected in only 2 of 17 sera by enzyme immunoassay. Our results indicate that NSE may be a useful marker for human RCC, especially for those tumors that have broken through the renal capsule.     

162例胃肠道间质瘤的临床病理学及免疫表型特征

目的阐明胃肠道间质瘤的临床病理学与免疫表型特征。方法收集１６２例胃肠道间质瘤临床病理学资料,其中４６例进行免疫组织化学染色。标记抗体为波形蛋白（ｖｉｍｅｎｔｉｎ）、ＣＤ３４、肌特异性肌纤蛋白（ＭＳＡ）、平滑肌特异性肌纤蛋白（ＳＭＡ）、Ｓ１００蛋白、神经特异性烯醇化酶（ＮＳＥ）、突触素（ＳＹＮ）、细胞角蛋白（ＣＫ）、癌胚抗原（ＣＥＡ）、白细胞共同抗原（ＬＣＡ）等１０种抗体。结果病理学上肿瘤起源于胃肠道肌层,直径为０．５～４３ｃｍ,５５％为恶性。免疫表型特征为ｖｉｍｅｎｔｉｎ,占１００％、ＣＤ３４,占６４％、ＭＳＡ,占４７％、ＳＭＡ,占４１％、ＮＳＥ,占６１％、Ｓ１００蛋白,占１９％、ＳＹＮ,占１５％。胃肠道间质瘤不表达ＣＫ、ＣＥＡ、ＬＣＡ。结论间质瘤为起源于胃肠道肌层的最常见间叶性肿瘤,消化道出血与腹部包块为最常见症状。最常见的细胞学特征为梭形细胞和上皮样细胞。肿瘤的大小、核分裂相是关系到肿瘤良恶性和患者预后、生存的最重要因素。免疫组化证实仅有部分肿瘤具有不完全的平滑肌、神经或双向分化特征。     

Immunohistochemical distribution of S-100 protein in tumors and tumor-like lesions of bone and cartilage

Various tumors and tumor-like lesions of bone and cartilage were examined for S-100 protein using the avidine-biotin-peroxidase complex (ABC) immunostaining method. The most intense reactivity for S-100 protein was found in well-differentiated chondrocytes of enchondromas, osteochondromas and chondrosarcomas, and in normal epiphyseal cartilage. S-100 protein was positive in both polygonal stromal cells and chondrocytes of chondroblastomas and in chondrocytes of mesenchymal chondrosarcoma. In osteosarcomas not only chondroblastic areas but also osteoblastic areas showed positive cells. Reticulum histiocytic cells of eosinophilic granulomas and chordoma cells were positive for S-100 protein. The study yielded three main conclusions: (1) S-100 protein could be the marker for tumors of cartilaginous origin and differentiation, notochord origin, and T-zone histiocyte origin; (2) chondroblastoma can be distinguished from other histologically confusing giant cell lesions by using ABC to detect S-100 protein; and (3) S-100 protein has some relationship with tumoral calcification not only in cartilaginous tumors but also in osteosarcoma.     

Immunohistochemical evaluation of uveal melanocytic tumors. Expression of HMB-45, S-100 protein, and neuron-specific enolase

The authors compared the immunohistochemical reactivity of 13 uveal nevi and 20 uveal melanomas for HMB-45, S-100 protein, and neuron-specific enolase (NSE) in formalin-fixed, paraffin-embedded sections. All 33 of the lesions were positive for HMB-45. The false-negative rates for S-100 protein and NSE were 21% and 18%, respectively. If only strongly positive reactions were considered, more than 50% of the tumors would be interpreted as negative for S-100 protein and NSE. Nevi stained with less intensity than melanomas using all three antibodies. The expression of HMB-45 appeared to be greater in active nevi than in inactive nevi. There was a weak association between S-100 protein reactivity and the ability of the uveal melanomas to metastasize (P = 0.1); however, the standard deviation of nucleolar area was a much better predictor (P = 0.02). These results indicate that pathologists will find HMB-45 to be a useful tool in differentiating uveal melanoma from nonmelanocytic tumors.     

胰腺实性假乳头状肿瘤的临床病理学分析

目的：探讨胰腺实性假乳头状肿瘤的临床病理学特点及免疫表型，方法：对4例胰腺实性假乳头状肿瘤临床资料进行回顾性复习。并采用免疫组织化学EnVision法检测肿瘤细胞Vim、CK8、CK18、Chromogranin、Sy、AAT、NSE、S-100的表达，结果：4倒患者均为女性．平均年龄30岁．肿瘤由乳头状和实性区混合构成，肿瘤细胞形态单一．免疫组化标记显示Vim，4例均呈弥漫性强阳性；AAT灶性强阳性；NSE三例阳性，一例阴性；Sy、Chromogranin和S-100 4例均阴性；CK8和CK18 一例散在弱阳性，另三例阴性。结论：胰腺实性假乳头状肿瘤是一种好发于青年女性、具有低度恶性潜能的肿瘤，免疫组织化学对胰腺宴性假乳头状肿瘤的诊断和鉴别诊断具有重要价值。     

Immunohistochemical study of neuron specific enolase expression in salivary-gland tumors

The immunoreactivity of monoclonal anti-neuron-specific enolase (MoAb NSE) on 10% formalin-fixed sections of normal human salivary glands and tumors were examined by the avidin-biotin-peroxidase complex (ABC) method. MoAb NSE staining of ductal and acinar cells of the normal salivary glands were, negative, and peripheral nerve fiber in the gland tissue showed strongly positive staining. In salivary gland tumors, pleomorphic adenoma (34 in total 68), myoepithelioma (15 in 35), monomorphic adenoma (7 in 10), adenolymphoma (15 in 23), mucoepidermoid carcinoma (3 in 16), acinic cell carcinoma (1 in 7), adenoid cystic carcinoma (12 in 20) and sialocarcinoma (4 in 15), stained focally for MoAb NSE staining. Frequency of occurrence for positive NSE activity varies among benign and malignant salivary gland tumors. In addition to MoAb NSE, S-100 protein and GFAP also demonstrated positive reactions in pleomorphic adenoma (Simpson et al Cancer 54: 1364-1369, 1984). The outer layer cells and/or peripheral cells of tubulo-ductal structure as well as modified myoepithelial cells and the cells of solid structure coexpressed with NSE, S-100 protein and GFAP. It is postulated that the salivary gland tumors particularly pleomorphic adenoma may be neuroectodermal in origin, arising from stem cells in intercalated duct segments.     

子宫卵巢性索样肿瘤免疫组化研究

[目的]探讨子宫卵巢性索样肿瘤的组织发生学。[方法]应用免疫组织化学LSAB法检测18例子宫卵巢性索样肿瘤石蜡切片中Keratin、EMA、CEA、Vimentin、Actin、Desmin、Myoglobin、CD34、S－100和NSE10种标记。[结果]性索上皮样细胞团Vimentin、Actin18例阳性,Desmin16例阳性,NSE4例阳性,CK和EMA各2例阳性。子宫内膜间质样细胞区Vimentin、Actin和desmin18例均为阳性,余则为阴性。[结论]子宫卵巢性索样肿瘤系由子宫多潜能间质细胞起源,向性索上皮样、子宫内膜间质样细胞和平滑肌细胞分化,而又不同于子宫体上皮和间叶成份混合性肿瘤、子宫内膜间质肿瘤和平滑肌肿瘤,建议独立分类。     

Chondroid chordoma versus low-grade chondrosarcoma of the base of the skull: can immunohistochemistry resolve the controversy?

The classification of cartilaginous tumors of the skull base, including chondroid chordoma and chondrosarcoma remains the subject of controversy. Critical review of the literature and our own experience of chordomas and cartilaginous tumors of the skull base led to the following conclusions: 1) Chondrosarcoma of the skull base is a distinct clinicopathological entity. The immunohistochemical staining pattern (cytokeratin negative, epithelial membrane antigen (EMA) negative) can be helpful in distinguishing it from chordoma with chondroid differentiation (cytokeratin positive, EMA positive). 2) The chondroid chordomas originally described by Heffelfingeret al. may have included some true chondrosarcomas with focal areas of myxoid chordomalike appearance. 3) Focal chondroid differentiation in chordoma is not such a rare phenomenon. Further study is needed to define whether chordoma with chondroid foci should be separated out from conventional chordoma as a distinct entity with a better prognosis.     

CK19,S-100和EMA在鉴别甲状腺乳头状癌与乳头状增生中的作用

目的：评估检测CK19、S-100蛋白和EMA在诊断甲状腺乳头状癌、滤泡性癌及乳头状增生中的作用。方法：65例甲状腺病变组织分别用CK19、S-100、EMA进行免疫组化染色。结果：在乳头状增生中，CK19、S-100和EMA均不表达。CK19在乳头状癌包括滤泡型乳头状癌中100％表达，在滤泡性癌中有22％的表达。S-100和EMA在经典型乳头状癌分别为61％、100％；滤泡型乳头状癌38％、54％和滤泡性癌44％，11％。结论：CK19结合S-100和EMA检查在诊断甲状腺病变中是有用的辅助手段。CK19在区分甲状腺乳头状癌和乳头状增生中是一个很好的标志物。     

TD-12 workshop report: characterization of monoclonal antibodies to neuron-specific enolase

Twelve antibodies to neuron-specific enolase (NSE) have been evaluated by four working groups. Human brain γγ-enolase, neuroblastoma-derived αγ-enolase, and recombinant γγ-enolase were used to determine antibody specificity and binding kinetics. All antibodies were found to be specific for the γ-isoform. It was possible to assign 11 of the antibodies to at least five epitope groups based on cross-inhibition experiments, QCM and SPR technology, and immunoassay combinations. Antibodies 9601 and 9602 showed the highest affinity for both native and recombinant γγ-enolase. Immunometric assays for both γγ- and αγ-enolase could be made by pairing 9601 with most of the other ISOBM antibodies. Antibodies differed in their ability to recognize native αγ-enolase, native γγ-enolase, and recombinant γγ-enolase. Some immunometric assay combinations appear to favor the detection of heterodimeric αγ-enolase over the homodimeric γγ-enolase. Although the majority of the antibodies failed to detect human NSE or recombinant NSE in Western blots, mAb 9601 recognized both, while E17 and 18E5 were specific for human NSE.     

Neural markers in carcinoma of the lung

Small cell carcinoma (SCC) is considered to be of neuroendocrine origin. Neurone specific enolase (NSE) and PGP 9.5 are markers of neural and neuroendocrine differentiation. S-100 protein is a marker of glial differentiation. The expression of these markers in endobronchial biopsy and lung tumour resection specimens was studied to see if any diagnostic, prognostic or therapeutic implications would emerge. Zamboni fixed endobronchial tumour biopsy specimens from 20 patients were examined. Twelve of these were cases of SCC and 8 were non-SCC. Of the 12 SCC, 7 were positive for NSE, 6 for PGP 9.5 and 5 for S-100 protein. Cases which showed a positive reaction for NSE had a mean survival of 9.1 months compared with 3.9 months for those with a negative reaction, but the number of cases is too small to assign any statistical significance. There was no difference in survival times between positive and negative reactors for PGP 9.5 and S-100 protein. All 8 cases of non-SCC showed positive reactions to all three markers. Of 32 formalin fixed lung tumour resection specimens 6 were cases of SCC, 25 non-SCC and 1 a chemodectoma. Three of the 6 cases of SCC showed positive staining for NSE, 3 for PGP 9.5 and 1 for S-100 protein. Of the 25 non-SCC, 10 were positive for NSE, 12 for PGP 9.5 and 6 for S-100 protein. The 1 chemodectoma stained positively for all three markers. Neuroendocrine markers are of little value in differentiating SCC from non-SCC. Positive staining for NSE in SCC may be an indicator of prolonged survival but further investigation is required.     

A reassessment of histologic classification and an immunohistochemical study of 88 retinoblastomas. A special reference to the advent of bipolar-like cells.

BACKGROUND. Despite perpetual efforts of investigators, the histogenesis of retinoblastoma is still in dispute and histologic classification satisfactorily predictive of prognosis does not seem to be in use. METHODS. The authors studied 88 cases of retinoblastoma clinicopathologically and immunohistochemically, paying special attention to the presence of a "bipolar-like cell" element that would be used as one of the criteria for the diagnosis of differentiated retinoblastoma. RESULTS. Twelve cases of retinoblastoma with the bipolar-like cell element in the absence of rosettes and 41 cases of the tumor with rosettes were classified as differentiated retinoblastomas. The other 35 cases without rosettes or bipolar-like cells were classified as undifferentiated tumors. Tumor cells forming rosettes usually had positive results for synaptophysin and neuron-specific enolase (NSE) and negative results for glial fibrillary acidic protein (GFAP) and S-100 protein; however, undifferentiated cells had negative results for these four antibodies. The bipolar-like cells had positive results for synaptophysin and NSE but negative results for GFAP and S-100 protein. Twelve tumors with bipolar-like cells that lacked rosettes showed no optic nerve invasion, and the patients had a significantly better prognosis (100% 5-year survival rate) than 35 patients with undifferentiated tumors (71% 5-year survival rate) (P < 0.01). CONCLUSIONS. The findings support a neuronal origin of the tumor and indicate that, not only the rosettes symbolizing the photoreceptor differentiation, but also other neuronal elements, such as bipolar-like cells, can be used as criteria for histologic classification of retinoblastoma.     

食管小细胞癌的临床病理,免疫组化及电镜观察

目的：探计食管小细胞瘤的临床病理特征、抗原表达及超微结构特点。方法：收集食管小细胞癌２８例，分析统计临床病理资料，每例均采用ＳＬＡＢ方法做７项免疫学标记，分别为ＣＫ、ＬＣＡ、Ｓ－１００，ＣＤ５６（神经细胞粘连分子）、ＣＨＡ（铬粒素）、ＮＳＥ（神经特异性烯醇化酶）、ＨＨＦ３５，５例取新鲜组织做电镜观察。结果：患者年龄以中老年多见，部位在中下段，病情发展快、转移早，预后差。林体形态为溃疡型、隆起型，镜     

Estrogen receptor-β regulates psoriasin (S100A7) in human breast cancer

We have previously observed a paradoxical relationship of the psoriasin/S100A7 gene with estrogen response in-vitro in ERα positive cells but its association with ERα negative status in-vivo raising the possibility that S100A7 might be regulated by ERβ in breast cancer. Using doxycycline-inducible ERβ and ERα expressing MCF-7 cells the hypothesis that psoriasin/S100A7 is ERβ regulated was investigated To explore the relationship between psoriasin/S100A7 and ERβ expression in-vivo, we also assessed a cohort of 233 ERα negative breast tumors using tissue microarrays and immunohistochemistry. Psoriasin/S100A7 was increased by 17β-estradiol (E2) following ERβ induction, in several clones of ERβ over-expressing but not in the original MCF-7 cells, nor clones over-expressing ERα. The effect of E2 on psoriasin/S100A7 was inhibited by 4-hydroxytamoxifen and ICI 182780 but not with a selective ERα antagonist. An ERβ selective-agonist but not an ERα selective-agonist, induced psoriasin/S100A7. This induction still occurred after stable down-regulation of ERα using siRNA in ERβ inducible cells. E2 increased psoriasin/S100A7 mRNA but cycloheximide treatment inhibited this effect. A relationship between ERβ and psoriasin/S100A7 was observed in the p53 immunohistochemically negative subset of invasive breast tumors in-vivo (r = 0.225, p = 0.046, n = 79). In conclusion we demonstrate that E2 induction of psoriasin/S100A7 can be specifically regulated through ERβ in-vitro and associated with ERβ in-vivo. These data support the hypothesis that psoriasin/S100A7 is specifically regulated by ERβ activity and could be useful to guide future therapies targeting ERβ in certain phenotypic subsets of breast cancers in-vivo.     

Odontogenic myxoma: clinico-pathological, immunohistochemical and ultrastructural findings of a multicentric series

The aim of this study was to analyze the clinico-pathological and immunohistochemical features of 62 cases of odontogenic myxoma (OM) diagnosed in three Oral Pathology Diagnostic Services in Latin America, as well as to describe the ultrastructural features of three of these cases. OM showed a wide age range (9-71 years), with a mean of 27.97 yr (SD: 11.01) and a male to female ratio of 1:2.2. Mandible was affected in 37 cases (59.6%) and maxilla in 25 (40.4%), with 61.3% located in the posterior region. Thirty-nine cases (62.9%) were multilocular and 23 (37.1%) unilocular. Size ranged from 1 to 13 cm, (mean: 5.2 cm). Thirty-seven multilocular (54.8%) and 6 unilocular lesions (26%) were larger than 4 cm (p<0.05). Epithelial islands were identified in 5 cases (8%) on H&E stained sections, but AE1/AE3 and CK14 disclosed these structures in 15 cases each (24.2%); CK5 was positive in 8 (12.9%); CK7 in 2 (3.2%) and CK19 in only 3 cases (4.8%). All cases were negative for CKs 8 and 18, S-100 protein, NSE and CD68, and showed a low index of expression of Bcl2 and ki-67 proteins (<1%). Mast cell antibodies showed these cells in 45 cases (72.6%). Myofibroblastic differentiation evidenced by myofilaments and fibronexi was found in one case out of the three studied by TEM and 29 cases (46.7%) were positive by immunohistochemistry for alpha actin. In conclusion, only a minority of OM had epithelial islands, and only 3 cases expressed CK 19, indicating an odontogenic epithelium origin. Immunohistochemical and ultrastructural findings suggest that OM is a mesenchymal neoplasm in which several factors may contribute to its pathogenesis, including myofibroblastic differentiation and the participation of mast cell products. However, further investigations are needed to better understand the participation of these elements in this particular neoplasm.