Immunohistochemical analysis of giant cell glioblastoma

Giant cell glioblastoma (GCG) is one of a group of rare tumors in which the cell population is abnormally large and includes multinucleated cells of gigantic sizes. Immunohistochemical studies were performed on four GCG cases and found that all giant cells and/or tumor cells were positive for glial fibrillary acidic protein (GFAP), S-100 protein, and vimentin, thus verifying the tumor's glial origin. The nuclei of multinucleated giant cells of three adult cases were frequently immunostained for proteins expressed during the cell cycle (proliferating cell nuclear antigen (PCNA) and Ki-67), thereby demonstrating the proliferative capacity of these cells. By contrast, those of a 12 year old girl expressed these cell cycle markers rather infrequently. Alpha I-anti-trypsin was detected with relatively high frequency in the giant cells, and its presence may explain their bizarre sizes and pericellular reticulin fiber formation. A literature review of 32 cases revealed that the GCG that occurs preferentially in young girls is a type of pleomorphic xanthoastrocytoma. By contrast, GCG in adult males has the same age incidence as ordinary glioblastomas and, as these, expresses high levels of cell cycle-related proteins. Thus, GCG, which is subclassified morphologically as ordinary glioblastoma, has distinct biological and clinical characteristics, with that in children requiring re-evaluation because of its similarities to pleomorphic xanthoastrocytoma.     

Immunohistochemical FHIT expression still exists in early lesions of basal cell carcinoma

In this study, we evaluated the expression of Fragile Histidine Triad (FHIT) in basal cell carcinoma (BCC). The FHIT locus was found to be altered in numerous types of cancer 6, 7, 18, 20, 22, 25 and 26. However, we found only one study dealing with FHIT expression in BCC [11].     

Immunohistochemical study of mononuclear phagocyte antigens in giant cell tumor of bone.

The cytogenesis of giant cell tumor of bone (GCT) was assessed by immunohistochemical methods. Three GCT were analyzed by a sensitive immunoalkaline phosphatase technique with a panel of monoclonal antibodies, including eight reacting with separate antigens previously found to be present on mononuclear phagocytes (MPs) and one specific for the endothelial marker, coagulation Factor 8. Among the MP-associated antigens evaluated were leukocyte common antigen (LCA), HLA-DR, C3b receptor, and C3bi receptor. Also incorporated in the panel were antibodies to MP-associated antigens with well-characterized tissue distribution but of currently unknown function. Constituent cells of the tumors varied in their reactions with the antibodies of the panel. Although mononuclear cells in tumor stroma were labeled with all of the antibodies against the MP markers, giant cells reacted strongly only with antibodies to LCA and the MP-associated antigen recognized by the antibody EBM11. Giant cells were weakly and focally labeled with antibodies (KB90 and UCHM1) against two additional MP-associated determinants and were unreactive with the remaining antibodies in the panel. Spindled stromal cells, which appeared to produce collagen, were not labeled with any of the antibodies in the panel. Only endothelial cells reacted with antibody to Factor 8. The results of this study suggest that giant cells of GCT are derived from stromal cells of mononuclear phagocyte lineage, and that the stromal precurser cells lose some, but not all, MP-associated antigens as they mature into giant cells.     

骨巨细胞瘤中骨保护因子及破骨细胞分化因子的表达

目的 检测骨巨细胞瘤中骨保护因子（OPG）及破骨细胞分化因子（ODF）mRNA的表达,并探讨多核巨细胞的来源及造成骨吸收的分子机制。方法 采用半定量逆转录－聚合酶链反应（RT－PCR）方法检测骨巨细胞瘤和正常骨组织中OPG、ODF及其辅助因子巨噬细胞克隆刺激因子、信号受体RANK mRNA的表达,并将两种组织中各因子的表达情况进行半定量比较。结果 正常骨组织中OPG、巨噬细胞克隆刺激因子、RANK mRNA有表达,ODF呈微弱表达;骨巨细胞瘤中OPG、ODF、巨噬细胞克隆刺激因子、RANK mRAN均有表达,ODF的表达非常丰富。骨巨细胞瘤中ODF与OPG的比值远远高于正常骨组织。结论 骨巨细胞瘤中的微环境具备破骨细胞形成及其促进骨吸收的必要条件,多核巨细胞的来源及其骨吸收功能与上述几种因子的表达有关。     

Immunohistochemical study of epidermal growth factor receptor expression in esophageal squamous cell carcinoma

Primary tumors from 31 patients with esophageal squamous cell carcinoma (ESCC) were immunohistochemically studied for the expression of markers of ESCC in order to define the clinical value of the levels of EGFR and HER-2 in the tumors. EGFR and HER-2 hyperexpression in the tumors of patients with ESCC was ascertained to be an important marker for the analysis of the clinical features of ESCC. There was an association of the elevated levels of EGFR and HER-2 in the tumors of ESCC patients with the presence of vascular tumor invasion (p = 0.006) and that with the poor outcome of the disease (p = 0.004). The findings suggest that estimation of changes found in EGRF and HER-2 expression in the tumors of patient with ESCC is of great interest for the individual prediction of the disease course and for the development of new approaches to treating these tumors, including targeted therapy against these tyrosine kinase receptors.     

Immunohistochemical expression of vascular endothelial growth factor (VEGF) and C-KIT in cutaneous melanocytic lesions

Vascular endothelial growth factor (VEGF) and C-KIT are involved in tumor progression in several human neoplasms. The aim of the present study has been to investigate their immunohistochemical expression in melanocytic lesions. We examined 11 compound nevi, 12 dysplastic nevi, and 18 melanomas. Immunostaining for VEGF was observed only in melanomas; c-kit expression was detected in melanomas (higher in radial than in vertical growth phase) and in nevi (predominantly in the junctional component). Our data indicate that assessment of VEGF expression might aid in the differential diagnosis between dysplastic nevi and melanomas. Moreover, VEGF might be a candidate for targeted therapy. The loss of c-kit expression might contribute to melanoma progression.     

Immunohistochemical evaluation of the cytoarchitecture of benign and malignant breast lesions.

Fifty-three breast lesions, which had been fixed in formalin and embedded in paraffin, were immunohistochemically analyzed with monoclonal antibodies to cytokeratin subtypes 1, 5, 10, 14 (34BE12), muscle-specific actins (HHF35) and antiserum to S100 protein, all of which have been used as markers for myoepithelial cells. With these antibodies, a continuous myoepithelial cell layer could generally be seen around the benign ducts and acini. In in situ carcinomas, such a layer could still be observed, though it was usually discontinuous and sometimes absent. In infiltrating carcinomas, no myoepithelial cell layer could be observed. In intraductal hyperplasias, scattered HHF35, 34BE12 and S100-positive cells could be seen amongst the proliferating intraductal cells. In in situ and infiltrating carcinomas, however, such cells could also be observed. This was seen especially with antibodies 34BE12 and S100, and to a lesser extent also with HHF35. Morphologically these cells seemed to belong to the malignant cell population. Although myoepithelial cell preservation is an important morphological parameter in the histological evaluation of breast lesions, the results suggest that the myoepithelial cell markers 34BE12, HHF35 and S100 cannot be used in the differential diagnosis between benign and malignant breast lesions in a straightforward manner. This is because in situ carcinomas have a more or less preserved myoepithelial cell layer, and because many infiltrating and in situ carcinomas contain a subpopulation of neoplastic cells expressing these markers, possibly signifying myoepithelial cell differentiation.     

IL-2 receptor expression in human lymphoid lesions. Immunohistochemical study of 166 cases.

Interleukin-2 (IL-2) receptor expression is a feature of T-cell activation and T-cell neoplasia. Expression of the IL-2 receptor in human lymphoid lesions was studied in a series of 166 immunophenotyped cases, including nodal and extranodal reactive lymphoid proliferations (44 cases), low-grade B-cell lymphomas (27 cases), intermediate and high grade B cell lymphomas (42 cases), peripheral T-cell lymphomas (13 cases), Hodgkin's disease (12 cases), histiocytic proliferations (15 cases), nonhematopoietic tumors (16 cases), and miscellaneous lesions (7 cases). Low levels of receptor expression were seen in reactive lymphoid lesions, low-grade B-cell lymphomas, and nonhematopoietic tumors (20%, 7%, and 25% of cases, respectively, with greater than 10% positive cells). High levels of receptor expression were seen in cases of peripheral T-cell lymphoma and histiocytic proliferations (86% and 100% of cases, respectively, with greater than 10% positive cells). Intermediate levels of expression were seen in Hodgkin's disease (including Reed-Sternberg cells) and some cases of intermediate and high-grade B-cell lymphomas (58% and 50% of cases, respectively, with greater than 10% positive cells). IL-2 receptor expression is not confined to T-cell neoplasia, but is also a feature of neoplastic and nonneoplastic histiocytic proliferations, Hodgkin's disease, and some intermediate and high-grade B-cell lymphomas. Biologic and therapeutic implications are discussed.     

Langerin在Langerhans细胞组织细胞增生症和非Langerhans细胞组织细胞性疾病中的表达

Langerhans细胞代表着树突抗原提呈细胞的一种亚型，主要位于各种器官的表皮和黏膜。该细胞因特征性表达CDIa抗原和胞质内Birbeck颗粒的存在而不同于其他亚型的树突状细胞。Birbeck颗粒的形成被认为是通过一种名为Langerin的凝聚素家族的新的Ⅱ型跨膜糖蛋白介导的。Langerin是Langerhans细胞和Langerhans细胞组织细胞增生症中病变细胞的一种高度选择性标记物，但对Langerhans细胞组织细胞增生症的特异性还没有明确。     

Immunohistochemical evaluation of alpha-catenin expression in human gastric cancer

E-cadherin (E-cad) plays a major role in the maintenance of cell-cell adhesion in epithelial tissues, and impaired E-cad expression correlates with tumour invasion and metastasis. Alpha-catenin (-cat), an undercoat protein of adherens junctions, binds to the cytoplasmic domain of E-cad and is essential for linking E-cad to actin-based cytoskeleton. We investigated E-cad and -cat expression in 60 human gastric cancers immunohistochemically. The 60 gastric cancers were classified into 18 (30%) in which -cat expression was preserved, and 42 (70%) reduced cases. The reduction of -cat expression was significantly related to dedifferentiation, depth of invasion, infiltrative growth and lymph node metastasis. We also examined the co-expression of -cat and E-cad. Seventeen (28%) tumours preserved both molecules [-cat(+)/E-cad(+)] and 33 (55%) tumours reduced both [-cat(–)/E-cad(–)], whereas 9 (15%) tumours exhibited -cat(–)/E-cad(+). The frequency of lymph node metastasis in -cat(–)/E-cad(+) tumour (67%) was significantly higher than that in -cat(+)/E-cad(+) tumours (24%) and was close to that in -cat(–)/E-cad(–) tumours (82%). The frequency of haematogenous liver metastasis in -cat(–)/E-cad(+) tumours (44%) was significantly higher than that in -cat(+)/E-cad(+) tumours (6%) or -cat(–)/E-cad(–) tumours (9%). Thus, in all E-cad(+) tumours, the frequency of lymph node and liver metastasis was higher in -cat(–) tumours than in -cat(+) tumours. -Cat expression is apparently better at predicting tumour invasion and metastasis than E-cad expression.     

Immunohistochemical expression of galectin-3 in benign and malignant thyroid lesions

CONTEXT: The expression of galectin-3, a human lectin, has been shown to be highly associated with malignant behavior of thyroid lesions. DESIGN: We studied the immunohistochemical expression pattern of galectin-3 in a variety of follicular-derived thyroid lesions (13 benign and 62 malignant), including Hürthle cell and follicular carcinoma, papillary carcinomas and variants, and anaplastic and poorly differentiated carcinomas. RESULTS: Immunoreactivity was strongest in papillary thyroid carcinomas, whereas staining was less intense in Hürthle cell and anaplastic carcinomas, and even weaker in the follicular variant of papillary thyroid carcinoma. Staining was absent or weak in the 3 follicular thyroid carcinomas and was negative in both insular carcinomas. In several tumors, staining was stronger at the advancing invasive edge of the lesion than in the central portion of the tumor. Galectin-3 was also expressed focally and weakly in reactive follicular epithelium and entrapped follicles in chronic lymphocytic thyroiditis. A variety of thyroid lesions showed prominent endogenous, biotin-like activity, which could cause flaws in interpretation if a biotin-detection system were used. CONCLUSION: We conclude that galectin-3 immunostaining, when used in biotin-free detection systems, may be useful as an adjunct to distinguish benign from malignant thyroid lesions.     

Immunohistochemical staining of papillary breast lesions.

The separation of ductal papilloma from intraductal papillary carcinoma of the breast on hematoxylin and eosin stained sections often presents diagnostic difficulty. Immunohistochemical staining is often employed in diagnosis, historically with smooth muscle actin (SMA). In this study, the staining characteristics of a panel of myoepithelial markers (calponin, p63, P-cadherin), were compared with SMA, and the epithelial expression of CD44s was assessed in 99 papillary lesions. SMA, calponin, and p63 demonstrated myoepithelial cells in 61%, 63%, and 65% of papillary lesions, respectively. However, specificity was quite variable. Calponin-stained stromal myofibroblasts (35% of cases), vessel pericytes (92%), and endothelial cells (69%), though each to a lesser degree than SMA. Calponin also showed cross reactivity with epithelium in 18% of cases. p63 was almost completely restricted to myoepithelial cell nuclei, and did not stain vascular smooth muscle or myofibroblasts. However, p63 stained the epithelial component in one papillary carcinoma, a basal layer of cells in 1 biphasic invasive carcinoma, and the cytoplasm in 1 case. P-cadherin stained both epithelial and myoepithelial cells. The epithelial expression of CD44s and did not distinguish papillomas from papillary carcinomas. Thus, P-cadherin and CD44s are not useful in the characterization of papillary lesions. Given increased specificity as compared with SMA, the combination of p63 and calponin is recommended for analysis of breast papillary lesions.     

Immunohistochemical analysis of biliary tract lesions.

The distinction among inflammatory, benign, and malignant lesions of the biliary tract can at times be difficult. Several methods have been used, including immunohistochemistry (IHC), with variable success. We evaluated a panel of IHC stains to determine their utility in discriminating between bile duct lesions. Formalin-fixed, paraffin-embedded 4-microm sections from 12 inflammatory lesions, 10 bile duct adenomas, and 13 bile duct carcinomas were immunostained using a modified avidin-biotin-complex technique after epitope enhancement using antibodies for p53, Ki-67, and bcl-2. For p53 and bcl-2, greater than 1% of cells staining positive was interpreted as positive. The proliferation index was calculated by determining the number of Ki-67-positive cells in a 1000 cell count. In the inflammatory group, 0 of 12 reacted with anti-p53, 2 of 12 were positive with anti-bcl-2, and the proliferation index with was 22.9% +/- 3.9%. Two of 10 bile duct adenomas showed reactivity with anti-bcl-2, and none were decorated with anti-p53 or Ki-67. In the carcinoma group, 6 of 13 were positive with anti-p53, 9 of 12 were positive with anti-bcl-2, and the proliferation index was 35.3% +/- 5.5%. The proliferation rates differed significantly between groups (P < 0.05). The presence of bcl-2 and p53 immunoreactivity coupled with a high proliferative rate in a biliary tract lesion suggests a malignant process. A panel using these antibodies may be useful in difficult cases.