摘要:

The distribution of basal lamina as identified by ultrastructural examination has been shown to be a useful discriminator for various types of mesenchymal tumors. Two hundred and two tumors, which included a wide range of benign and malignant soft-tissue and bony tumors, were subjected to immunostaining for type IV collagen and laminin, both major components of basal lamina. Distinctive patterns of basal lamina distribution were observed, particularly with antibodies to type IV collagen. Peripheral nerve sheath tumors displayed characteristic distinct and continuous basal lamina investing individual tumor cells, allowing their separation from smooth-muscle tumors in which the basal lamina was often fragmented into long runs of variable thickness. Tumors with myofibroblastic differentiation had delicate, highly fragmented basal lamina parallel to the cell membranes, whereas no staining was seen around the cells of bony and chondroid tumors, spindle cell melanomas, fibrosarcomas, malignant lymphomas, and primitive/peripheral neuroepithelial tumors. Distinctive basal lamina surrounded neoplastic vessels, and it was also present around the glandular structures and cells of synovial sarcoma and epithelioid sarcoma. Immunostaining for basal lamina, particularly with anti-type IV collagen antibody, is a useful diagnostic discriminant in the diagnosis of soft-tissue tumors, particularly spindled and pleomorphic tumors, which may be difficult to distinguish from histologic features alone.

ISSN:1062-3345    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The morphologic distinction between salivary gland mixed tumor (MT), polymorphous low-grade adenocarcinoma (PLGA), and adenoid cystic carcinoma (ACC) can be difficult, especially on small amounts of material. To determine whether immunohistochemical features might help in this differential, we characterized the staining pattern for these three tumors using antibodies to Ki-67 (MIB1), BCL2, p53, and S-100 proteins. We immunostained 34 MTs, 30 PLGAs, and 35 ACCs. The ACCs had significantly more tumor cells positive for Ki-67 (MIB1) (medians 20-50%) than both PLGAs (median, 1.0%) and MTs (median, 1.0%) (each p value < 0.0001). Within the group of ACCS, the percentage of positive staining correlated with increasing histologic grade (grade 1 = 20% and grade 2 = 30% compared with grade 3 = 50%; each p < 0.01). S-100 immunostaining was strongly positive in both MTs (median, 75% tumor cells positive) and PLGAs (median, 82.5%), but it was relatively low in ACC relative to MT and PLGA (medians, 1-5.5%; p values from 0.015-<0.000001). BCL2 was positive in all tumors, although staining intensity was significantly greater in the ACCs (p values from 0.065-<0.000001). p53 immunostaining was absent to low (<2% of tumor cells) in MTs and PLGAs, a value significantly less than the immunostaining found in ACCs (p values from 0.048-0.00013). Within the ACCS, p53-positive cells appeared to increase significantly with increasing histologic grade (for grade 1 vs. grade 2 ACC, p = 0.018). In conclusion, MT and PLGA showed low Ki-67 (MIB1) and p53 immunostaining but frequent and strong S100 protein immunoreactivity. ACC showed relatively high Ki-67 (MIB1) and more intense BCL2 immunoreactivity, and the percentage of p53 immunostaining increased with increasing ACC histograde. S100 was less intense and less frequent in ACC compared with MT and PLGA. These findings suggest that Ki-67 (MIB1), S100, and BCL2 immunohistochemical stains are useful for separating ACC from PLGA and MT. Also, deregulation of proliferation and possible mutations in p53 may contribute to the greater malignancy of ACC compared with MT and PLGA.

ISSN:1062-3345    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Expression of estrogen (ER) and progesterone (PR) receptors has traditionally been associated with hormone-responsive organs, such as breast, ovary, and endometrium, and carcinomas arising therefrom. More recently, examples of “unexpected” ER or PR expression have been reported, particularly in tumors of endocrine tissues, such as thyroid and pancreatic islet cells. We tested the hypothesis that neuroendocrine tumors of various primary and metastatic sites might also express ER or PR or both by performing a retrospective immunohistochemical study in a series of 59 formalin- or mechacarn-fixed neuroendocrine carcinomas of various sites, including lung, skin, gastrointestinal and female genital tracts, and including carcinoid and atypical carcinoid tumors, small cell carcinomas, and Merkel cell carcinomas. We employed the anti-ER monoclonal antibody 1D5 and the anti-PR monoclonal antibody PgR1A6 using standard immunohistochemical techniques after microwave-based heat-induced epitope retrieval. Two of 28 carcinoid tumors demonstrated ER positivity; six of 30 cases were positive for progesterone receptor only. In addition, PR expression was found in one of two cases of atypical carcinoid, in five of 25 cases of small cell carcinoma, and in one of two cases of Merkel cell carcinoma. None of the atypical carcinoids, small cell carcinomas, or Merkel cell carcinomas were ER positive. In most cases, the fraction of tumor cell nuclei that were positive was <50%. These studies add the spectrum of neuroendocrine tumors that can express these hormone receptors. Similar to the pattern previously described in the subsets of meningiomas and islet cell tumors, PR but not ER is detectable in most cases. These results underscore the caution that should be exercised in determining tissue origin of metastatic carcinomas based only on detection of hormone receptors by immunohistochemistry.

ISSN:1062-3345    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The purpose of the present study was to evaluate the prognostic utility of somatostatin, gastrin-releasing peptide, neuropeptide Y, and opioid peptide expression in sporadic medullary thyroid carcinoma. To this end, we submitted to statistical analyses the immunocytochemical data on a consecutive series of 109 such tumors. In univariate analysis, a significantly increased risk of disease progression was present in patients with opioid-immunoreactive tumors. An increased, though statistically insignificant risk of death was also found for patients with neuropeptide Y- or opioid-immunoreactive tumors. Multivariate analyses were performed by adding the four peptide variables to the final (reference) models obtained in an earlier work on the same case series in which 18 clinicopathologic variables had been taken into account. This addition did not change the prognostic impact of the variables considered in the two reference models, nor did it seem to increase the prognostic information, since the adjunctive contribution of each variable (as assessed by the likelihood ratio test) was not statistically significant. It is concluded that expression of somatostatin, gastrin-releasing peptide, neuropeptide Y, and opioid peptides is of no prognostic value in patients with sporadic medullary thyroid carcinoma.

ISSN:1062-3345    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

To assess the relationship between cell death and cellular proliferation in skin tumors, we analyzed cell death by apoptosis in 105 surgically resected skin carcinomas, including 43 basal cell carcinomas (BCCs), 49 squamous cell carcinomas (SCCs), and 13 Merkel cell carcinomas (MCCs) using the terminal deoxynucleotidyl transferase end-labeling method. Immunostaining for Ki-67 with MIB-1 antibody and for bcl-2 and p53 was also performed. BCCs had the highest apoptosis index (AI), which was twofold greater than the AI of SCCs. The AI and proliferative index (PI) were inversely related for BCCs and SCCs. MCCs had the highest PI among the three types of tumors. Although all tumor groups expressed p53 and bcl-2, the greatest number of cases expressing p53 and the smallest number of cases expressing bcl-2 were among SCCs. These results indicate that the AI and PI are inversely related in BCC and SCC. Merkel cell neuroendocrine carcinomas have a very high PI, which correlates with their more aggressive clinical course.

ISSN:1062-3345    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

An external quality study involving 57 pathologists at 13 departments of pathology in western Denmark was performed. Each department received 12 unstained sections of 13 diagnostically problematic cases (multitumor method), one section to use for a primary morphological hematoxylin and eosin diagnosis and the 11 remaining sections for immunohistochemistry. The primary morphological diagnoses and final diagnoses based on immunohistochemical panels were collected in addition to information about the primary antibodies, immunohistochemical methods, and panels used. Compared with “pure” morphology, immunohistochemistry proved to be very valuable and provided important information for definitive typing in 76% of these tumors. Diagnostic accuracy was especially improved in 38% of the cases, in which the list of differential diagnoses included undifferentiated carcinoma versus malignant lymphoma, metastatic melanoma (amelanotic) versus sarcoma, and cases of prostate-specific antigen-positive tumors. Comparison of the 143 immunohistochemically stained multitumor sections from the 13 departments showed similar patterns, with only a few false positives or false negatives. Errors in technique or lower sensitivity of the two-stage-immunoperoxidase method may explain the few cases with false-negative results. The antibodies from different sources did not affect the quality of the stainings. Selection of the most appropriate antibody panel and interpretation of the immunohistochemically stained sections were the most important factors that influenced the final diagnostic results.

ISSN:1062-3345    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Cyclin D1/bcl-1 is overexpressed in mantle cell lymphoma. Demonstration of this nucleoprotein by immunohistochemistry may be diagnostically useful. We evaluated the recently described sonication-induced method of epitope retrieval and compared it with microwave heat-induced epitope unmasking. The strongest staining intensities and lowest background staining were achieved when both epitope unmasking methods were combined.

ISSN:1062-3345    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The ability to accurately demonstrate intermediate filament proteins (IFs) in formalin-fixed tissues is of great importance in the histodiagnosis of neoplasms owing to the highly conserved and cell lineage-specific pattern of expression of these proteins. In this study, we evaluated the use of enzymatic and heat epitope retrieval methods for improving the immunoreactivity of the IFs fixed at different time intervals in formalin. Normal tissue specimens were fixed in formalin for 4, 24, and 48 h and in 70% ethanol as controls. The IFs were reacted with the following monoclonal antibodies: anti-cytokeratin antibodies following monoclonal antibodies: anti-cytokeratin antibodies KA4 (reactive with cytokeratins 14, 15, 16, and 19) and 10.11 (reactive with cytokeratins 8 and 18), anti-vimentin, anti-desmin, anti-glial fibrillary acidic protein (GFAP, polyclonal), and anti-neurofilament (NF). All IFs had marked loss of reactivity with each monoclonal IF antibody after 24-48 h of fixation, except GFAP, which retained its reactivity with the polyclonal GFAP antibody used. The cytokeratin immunoreactivity for both anti-cytokeratin antibodies, KA4 and 10.11, was completely recovered by predigestion with protease 1 but was less effectively enhanced by microwave heating. The other IFs tested greatly benefited from heat epitope retrieval in citrate buffer (0.01 mol/L) at pH 6. Protease 1 worked less well for these IFs and completely destroyed vimentin and desmin reactivity. Unexpectedly, microwave heating of fixed specimens of kidney and liver in Tris buffer (0.5 mol/L) at pH 10 produced a strong, granular staining artifact that was due to the enhancement of avidin binding to endogenous biotin. This artifactual staining was successfully blocked by application of purified avidin before the addition of avidin-biotin-peroxidase complex. In conclusion, this study reemphasizes the importance of testing individual antibodies using the various conditions of fixation and epitope recovery.

ISSN:1062-3345    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Heat-induced antigen retrieval has become a widely used method to enhance reactivity between antibodies and their epitopes in paraffin-embedded tissue sections. The formation of avidin-biotin complexes are used routinely to detect the presence of bound antibodies. We report the unmasking of endogenous avidin-binding activity in paraffin-embedded hepatic and renal tissue after microwave treatment. Incubation of sections with free biotin followed by avidin inhibits this endogenous avidin-binding activity and does not interfere with subsequent antibody staining reactions. These findings emphasize the need for appropriate negative controls and caution when interpreting results following heat-induced antigen retrieval methods.

ISSN:1062-3345    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Endogenous avidin-binding activity (EABA), usually due to endogenous biotin present in tissues, can be a cause of false-positive staining artifact in immunohistochemical procedures that employ avidin or streptavidin-conjugated detection systems. Because of the localization of biotin in the mitochondrial enzyme pyruvate carboxylase, this artifact is most prominent in the study of cells or tissues that are metabolically active and have numerous mitochondria, such as liver and kidney. It is particularly prominent in oncocytic neoplasms because of their high content of mitochondria, but can be blocked by preincubation of the sections with dilute avidin solution, followed by incubation with dilute biotin solution, before the application of the primary antibody. Commercially available kits containing these reagents are available, but they are expensive. Additionally, purified avidin needed to prepare one's own reagents is extremely expensive (over $3400 per gram). Since avidin is isolated from egg whites, we hypothesized that diluted egg whites or egg substitutes purchased at food stores might be effective as an alternative to commercially available (and expensive) avidin reagents. In this report, we describe the use of this material as an effective and extremely economical substitute for commercial avidin reagents in EABA blocking procedures. The best results were obtained by using diluted egg whites. We also illustrate how heat-induced epitope retrieval (HIER) procedures markedly enhance the intensity of EABA, and that the intensity of EABA can vary with the particular HIER solution that is employed. An EABA artifact could be easily misinterpreted as true immunoreactivity if the negative control slides are not subjected to HIER procedures, which underscores the importance of always subjecting the negative control slides to the same HIER procedures used on the antibody stains for each case.

ISSN:1062-3345    

出版商:OVID    

年代:1997

数据来源: OVID