c-erbB-2 proto-oncogene product.
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Chondrosarcoma↗
Biomedical subjects
H Battifora
Publications and source records attributed to H Battifora.
The checkerboard tissue block. An improved multitissue control block.
We describe an improved method of embedding a large number of tissue samples in a single, normal-sized paraffin block. Because the tissues are evenly distributed in a checkerboard arrangement, they can be readily identified by their position in the resulting sections. This device permits rapid and inexpensive screening of new histologic reagents, and facilitates intra- and interlaboratory quality control.
Fixatives↗
Tumor immunophenotype: comparison between primary neoplasm and its metastases.
Monoclonal antibodies (MAb) are firmly established diagnostic adjuvants both in vitro and in vivo. Their potential for immunotherapy is highly promising. Antigenic heterogeneity of cells within the same tumor is a well known phenomenon; however, no large-scale studies are available to ascertain to what degree metastases maintain the immunophenotype of the primary tumors. For that purpose, we studied 54 commonly epithelial malignancies using immunohistochemistry (IHC) with a panel of seven frequently used MAb recognizing a gamut of membrane and cytoplasmic antigens (AE-1, CAM 5.2, B72.3, MC10, anti-carcinoembryonic antigen (anti-CEA), epithelial membrane antigen (EMA), and human milk fat globule (HMFG)). The number of metastases per primary tumor ranged between 1 and 26, with a total of 344 tissues studied. Metastases were located in regional and distal lymph nodes as well as in a diversity of organs (pancreas, adrenal, colon, spleen, soft tissues, etc). Only those cases in which all the tissues were obtained from a single surgical procedure and, therefore, uniformly fixed and processed, were selected. All the metastases from three cases (5.5%) were found to express one or two antigens not present on their primary. In no case did all metastases from a positive primary become negative for one MAb. Twelve cases (18.5%) showed modifications of the phenotype in one or more metastases. This study demonstrates that a broad phenotypic variation does not follow when tumors metastasize, and that it is, therefore, safe to foretell the metastatic immunophenotype based upon that of the primary tumor.
Antibodies, Monoclonal↗
Does rapid microwave fixation improve immunohistochemistry?
Microwave fixation in dilute aldehyde solution has been reported to be superior to fixation in formaldehyde for the preservation of antigens. We studied antigen preservation among tissues which were soaked in formaldehyde, dilute aldehyde, alcohol, and saline solution with or without microwave irradiation. Microwave fixation was found to be superior to conventional formaldehyde fixation with regard to antigen preservation. However, there was no detectable difference in immunostaining between any of the irradiated and nonirradiated alcohol-, aldehyde-, or even saline-treated tissues. Microwave-irradiated tissues, regardless of the fixative employed, displayed a tendency for tissue disintegration upon protease treatment, as is commonly seen in alcohol-fixed tissues. Our results suggest that the apparent improvement in antigen preservation when microwave fixation in dilute aldehyde solution is used is largely attributable to the fixation in alcohol during the graded alcohol dehydration steps in the tissue processor, rather than to any demonstrable effect of the microwave radiation per se.
Fixatives↗
Misuse of the term 'expression'.
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Antigens, Differentiation↗
Quality control in immunohistochemistry. Report of a workshop sponsored by the Biological Stain Commission.
Although immunohistochemical methods are increasingly applied in diagnostic histopathology, there has been little standardization or quality control of immunoreagents; and published reports have not standardized Material and Methods for meaningful comparisons of results among clinicians. The Biological Stain Commission-sponsored workshop was convened to address the following issues: a manufacturers' testing program for probity of commercial antibodies, development of a manual for performance criteria and quality control assurance procedures, standardization of package inserts, standardization of information provided in the Materials and Methods sections of publications, establishment of a reagent and procedure clearing house, study of the effects of different fixation regimes on tissue antigens, and investigation of the environmental conditions needed for antigen-antibody interaction. The recommendations of the ad hoc committee and their implications for the future are discussed.
Antigen-Antibody Complex↗
Direct sequencing analysis of exon 1 of the c-K-ras gene shows a low frequency of mutations in human pancreatic adenocarcinomas.
We have applied direct dideoxy sequencing of DNA fragments amplified in vitro by the polymerase chain reaction to the detection of mutations in exon 1 of the c-K-ras gene in human pancreatic adenocarcinomas. Four fresh frozen primary tumors, one metastatic tumor, and twelve formalin-fixed paraffin embedded tumors were analysed. Only three cases showed a possible mutation in codon 12 in a small population of cells, in contrast to the high frequency reported for this alteration with the RNAase A protection assay and allele-specific oligoxynucleotide hybridization. No major difference in sensitivity was found between DNA sequence analysis, and the latter method. Our results suggest that if c-K-ras mutations are indeed present in pancreatic adenocarcinomas at the high frequency reported by others, they must be confined to a small fraction of the cell population to escape detection by direct sequencing. Such a phenomenon would have implications for c-K-ras mutations in the pathogenesis of pancreatic adenocarcinomas.
Adenocarcinoma↗
Monocytoid B-cell lymphoma.
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B-Lymphocytes↗
Primary osteosarcoma of the lung. A reappraisal following immunohistologic study.
Five neoplasms were initially believed to represent primary osteosarcomas of the lung. Of the five cases, two were reinterpreted as carcino-sarcomas based on the identification of epithelial elements on further histologic sectioning and immunohistologic study in one and on immunohistologic study alone in the second. The differential diagnosis of carcinosarcoma should be considered for any lesion believed to represent a primary sarcoma of the lung, and in some cases carcinomatous elements may only be demonstrable by immunohistologic means.
Aged↗
A unique pattern of proto-oncogene abnormalities in ovarian adenocarcinomas.
Twelve cases of ovarian adenocarcinoma were studied for alterations in proto-oncogenes, and a unique pattern of altered ras proto-oncogenes was observed. Amplification of ras-Ki was found in three of seven ovarian tumors and amplification of ras-Ha in one of 12. In contrast, ras-Ha amplification was not found in any of the 334 other tumors and ras-Ki amplification was only seen in breast cancer at a frequency of 3%. Other proto-oncogenes altered in ovarian adenocarcinomas included c-myc and c-erbb-2. Proto-oncogene abnormalities were more frequent in aggressive tumors of high histologic grade.
Adenocarcinoma↗
Angiosarcoma of the gastrointestinal tract. A report of three cases.
Three cases of angiosarcoma in the stomach, small bowel, and colon, respectively, are reported. The gastric lesion occurred many years after historic evidence of cutaneous Kaposi's sarcoma. Two of the three lesions exhibited multifocality, and all demonstrated aggressive biologic courses. The varied histologic features of angiosarcoma make this diagnosis difficult to establish in an unusual location such as the gastrointestinal tract. The use of immunohistochemistry for a panel of antibodies, particularly the successful reaction with Factor VIII-related antigen, is important in evaluating light microscopically unusual tumors. A delicate framework of collagen type IV was elicited in each case, but ultrastructurally correlated with short segments of basal lamina in one case. This suggests that the absence of the traditional morphologic expression of basal lamina does not preclude its presence and emphasizes the sensitivity of immunohistochemistry. The lack of previously reported cases of gastrointestinal angiosarcoma may be because the tumor is underrecognized or because it is truly a rare occurrence.
Aged↗
Alterations of class I HLA genes in human colon cancers.
Alterations of HLA class I genes were found in 3 of 12 human colon cancers. Rearrangements in HLA class I genes were observed in 2 cancers and amplification of HLA-coding genes was observed in 1 cancer. All 3 cancers were at an advanced stage. No examples of amplification or rearrangement in the HLA genes were found in 10 other tumours of diverse types. No alterations in the beta 2-microglobulin gene were observed in 22 human solid tumours included in this study. The association between alterations in HLA genes and proto-oncogenes in these tumours is discussed.
Adenocarcinoma↗
Insensitive test for keratins.
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Adenocarcinoma↗
Signet-ring cell melanoma. A rare morphologic variant of malignant melanoma.
We recently received in consultation a lymph node involved by metastatic malignant melanoma with unusual and previously undescribed morphologic features. The neoplastic cells had a striking signet-ring appearance, similar to the signet-ring cells normally seen in mucin-producing adenocarcinoma and signet-ring cell lymphoma. Review of our consultation files of malignant melanomas revealed an additional case in which the neoplastic cells had a signet-ring cell appearance. Electron microscopic studies revealed that formation of signet-ring cells is caused by the presence of abundant vimentin filaments in the cytoplasm of neoplastic cells. Immunologic studies using a series of monoclonal and polyclonal antibodies, including S-100 protein, HMB-45, vimentin, cytokeratin, leukocyte common antigen, and Leu-M1, on both cases clearly established the diagnosis of this morphologically unusual variant of malignant melanoma for which we propose the term "signet-ring cell melanoma."
Adult↗
Expression of the antigenic determinant recognized by the monoclonal antibody 44-3A6 on select human adenocarcinomas and normal human tissues.
The IgG1 monoclonal antibody, 44-3A6, was raised against the human lung adenocarcinoma cell line, A549. It has been shown to react with a 40,000 MW protein found on the cell surface, which is preserved in formalin-fixed paraffin-embedded tissues. A recent study of pulmonary carcinomas utilizing immunohistochemical methods showed exclusive binding to lung adenocarcinomas, subsets of neuroendocrine tumors, some carcinoids and a subset of large cell carcinomas. Reactivity was not seen in squamous cell carcinomas and small cell neuroendocrine carcinomas. In addition, melanomas, sarcomas and hematologic malignancies do not express this antigen. We now report on the reactivity pattern of 44-3A6 in adenocarcinomas of nonpulmonary primary sites and in normal adults organs. Strong diffuse staining of neoplastic cells in adenocarcinomas of the stomach, colon, pancreas, gallbladder and breast was noted. Adenocarcinomas arising in the endometrium, ovary, kidney, prostate, thyroid and liver were either negative or showed weak and/or focal reactivity. Strong staining patterns were even noted in adenocarcinomas which had an 'undifferentiated' component; i.e., lacking well-defined glandular elements. Immunoreactivity was noted in epithelial cells in several tissues from which these adenocarcinomas arose including the bronchial tract, stomach, small intestine, pancreas and colon, whereas epithelial cells from the endometrium, kidney, ovary, prostate and thyroid were negative or showed diffuse weak immunoreactivity. Our finding indicate that monoclonal antibody 44-3A6 recognizes an epithelial antigen on subsets of normal as well as transformed glandular epithelia. The differential pattern of expression of its target antigen probably reflects differences in tumor genesis and/or differentiation.
Adenocarcinoma↗
Clinical applications of the immunohistochemistry of filamentous proteins.
The past few years have seen great progress in our knowledge of the biology and the chemistry of intermediate filaments and other filamentous proteins. This has translated into the development of antibodies that, together with new, highly sensitive immunohistochemical methods, have resulted in much improved diagnostic accuracy. New, more specific antibodies to these and other useful markers will no doubt be developed in the future. More efficient techniques for screening of these antibodies will contribute to their rapid evaluation. Libraries of antibodies that identify subclasses of filamentous proteins will very likely become routine tools in the histopathology laboratory in the near future. Moreover, as the chemical structure of the proteins that form the complex family of intermediate filaments becomes better understood, and the DNA sequences coding them are determined, it may become feasible to use molecular genetic approaches such as in situ hybridization to gain further insight into neoplastic processes of unclear histogenesis and to develop more precise diagnostic and taxonomic instruments. Nevertheless, it is worth repeating that application of these molecular tools cannot be successful unless it is backed by a thorough understanding of the principles of histopathologic diagnosis that have been painstakingly established by generations of anatomic pathologists.
Actins↗
Immunophenotypic diagnosis of leiomyosarcomas and rhabdomyosarcomas with monoclonal antibodies to muscle-specific actin and desmin in formalin-fixed tissue.
Two fibrillary proteins, muscle-specific actin (MSA) and desmin, are found only in cells of smooth and skeletal muscle lineages. Among the monoclonal antibodies (MAbs) to these antigens which we have tested, we found several to be reactive in formalin-fixed, paraffin-embedded sections. This finding widened the possibility of using these MAbs in routine diagnostic surgical pathology for the immunodiagnosis of rhabdomyosarcomas (RMS) and leiomyosarcomas (LMS). We therefore conducted a comparative study of three such MAbs which are available commercially and which we applied to paraffin-embedded, formalin-fixed tissues from 15 patients with RMS and 19 patients with LMS. The case selection criteria included typical light-microscopic appearances as well as immunoreactivity with at least one of the MAbs. MSA was detected in all cases of RMS and LMS, whereas desmin was reactive in 12 of 13 RMS and 10 of the 19 LMS. (Desmin antigenicity was judged to be lost in two RMS, since the vascular smooth-muscle tissue present in the specimens failed to react with these antibodies.) In LMS, desmin tended to show focal positivity, whereas the MSA in the same specimens was diffusely positive. These results demonstrate the utility of MAbs for confirmation of the muscle lineage of LMS and RMS in formalin-fixed, paraffin-embedded tissue. The results also indicate that, with the MAbs tested, the antigenicity of MSA is preserved more consistently than that of desmin in formalin-fixed, paraffin-embedded tissue, and that MSA is a more sensitive marker for the detection of muscle differentiation than is desmin, especially in LMS.
Actins↗