Biomedical subjects
Publications and source records attributed to M Nadji.
The applications of tumor markers and steroid receptors in gynecologic neoplasms are described. The value of immunohistologic techniques in the histogenetic assessment of gynecologic neoplasms is examined. Approaches to the diagnosis of similar-appearing lesions are presented.
Of 122 mouse monoclonal antibodies selective for human breast cancer, 13 immunoprecipitated an acidic glycoprotein from SK-Br-3 and ZR-75-30 human breast cancer cells. The antigen (BCA200) migrates with an apparent molecular weight of 200,000 on reducing and 180,000 on nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting a single polypeptide chain with a folded domain stabilized by a disulfide bond. Cross-blocking and sandwich immunoassays detected at least three distinct antigenic determinants on BCA200. Scatchard experiments measured 1,000,000 to 5,000,000 antigen copies per SK-Br-3 cell. The tissue distribution of BCA200 was studied using two monoclonals to different epitopes. Neither antibody stained any cells in human blood. When frozen sections of 20 normal human tissues were immunoperoxidase stained, the only positive structures were mucinous glands of colon, transitional epithelium of bladder, sweat glands of skin, and acinar epithelium of breast. Antibody 454C11 stained 16 of 21 breast tumor frozen sections and 9 of 12 breast cancer cell lines, while antibody 520C9 stained 5 of 20 breast tumors and 4 of 10 breast cancer lines. Cross-reaction was observed with lung, prostatic, pancreatic, endometrial, and ovarian cancer, but not with lymphoma, melanoma, colon, stomach, bladder, or esophageal cancer. When conjugated to ricin A chain, 10 of 13 antibodies produced immunotoxins selectively cytotoxic to SK-Br-3 breast cancer cells.
To investigate the value of different tissue markers in the histologic diagnosis of hepatic tumors, we performed immunoperoxidase stains for alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT), carcinoembryonic antigen (CEA), and an erythropoiesis-associated antigen (ERY-1) on formalin-fixed, paraffin-embedded samples from 107 primary and metastatic tumors of the liver. AFP was present in 17% of the hepatocellular carcinomas, in 7% of the metastatic carcinomas, and in none of the cholangiocarcinomas. AAT was present in 41% of the hepatocellular carcinomas, in 37% of the cholangiocarcinomas, and in 50% to 70% of the metastatic carcinomas of the liver. Intracytoplasmic CEA was found in 75% of the cholangiocarcinomas, in 92% to 100% of the metastatic carcinomas, and in only one of the mixed hepatocellular-cholangiocarcinomas. ERY-1 was present in 89% of the hepatocellular carcinomas, whereas none of the cholangiocarcinomas or metastatic carcinomas stained for this marker. We conclude that immunohistochemical assays for AFP and AAT are of limited value in the differential diagnosis of hepatic tumors. However, immunohistochemical stains for ERY-1 and CEA can be valuable in differentiating hepatocellular carcinomas from metastatic tumors.
An immunohistochemical study was conducted on the number and distribution of C-cells in the nonneoplastic thyroid tissue adjacent to tumors of follicular cell origin. It consisted of 49 cases, of which 25 were papillary carcinomas, 22 were follicular adenomas, and 2 were follicular carcinomas. Twenty normal adult thyroids from the Broward's Medical Examiner's morgue served as controls. In 17 of the 49 cases (34.6%), there was a statistically significant increase in the number of C-cells in the normal-appearing thyroid tissue adjacent to follicular cell tumors, with at least 50 C-cells in one low power field, while only one of 20 normal thyroids had a similar number of cells. (P = .02; chi 2 = 5.05). In two tumor cases there were more than 100 C-cells in several low power fields with formation of small C-cell nodules similar to those described in the type II Multiple Endocrine Neoplasia Syndrome (MEN). It was concluded that the nonneoplastic thyroid tissue adjacent to 34.6% of tumors with follicular cell phenotypes contains significantly more C-cells than those present in normal adult thyroids. The possible pathogenesis and clinical significance of these findings are discussed.
Malignant angioendotheliomatosis is a rare, systemic, usually fatal disease characterized by a massive proliferation of large, bizarre-looking mononuclear cells within small and medium-sized blood vessels. The histogenesis of the neoplastic cells has been the subject of long-standing controversy since the disease's initial description. Early investigators concluded that the entity represented a neoplasm of endothelial cells, but recently others have suggested that it is of lymphoid origin. We studied a case of malignant angioendotheliomatosis by Southern blot hybridization analysis which showed clonal rearrangements of the immunoglobulin heavy-chain gene strongly suggesting a B-lymphocyte origin. Our results provide additional evidence that malignant angioendotheliomatosis is an intravascular malignant lymphomatosis.
Forty two carcinomas of the gallbladder and 25 mucinous cystadenocarcinomas of the pancreas were analyzed using silver stains and immunohistochemical techniques. Fourteen (33.3%) gallbladder carcinomas had argyrophil and argentaffin cells and 17 (40%) contained endocrine cells as shown by immunoperoxidase stains. The gallbladder tumors that had the largest number of endocrine cells were the well differentiated adenocarcinomas with colonic features. The most common endocrine cell in these tumors was the serotonin-containing (EC) cell followed by somatostatin-containing cells and cells that reacted to pancreatic polypeptide and gastrin. Intestinal metaplasia with pseudopyloric gland hyperplasia was present in the gallbladder mucosa adjacent to 11 carcinomas and had an endocrine cell population similar to that of the tumors. Endocrine cells were demonstrated in 18 (70%) of the 25 mucinous cystadenocarcinomas of the pancreas by the immunoperoxidase method although only 9 had argyrophil and argentaffin cells. The population of endocrine cells in these mucinous pancreatic tumors was similar to that found in gallbladder carcinomas. Endocrine cells were more numerous in areas with colonic-type glands, goblet cells and Paneth cells. The secretory products of the endocrine cells in these gallbladder and pancreatic tumors did not give rise to systemic endocrine manifestations. The presence of endocrine cells in these tumors can be explained on the basis of intestinal differentiation.
Langerhans cells (LC) were identified and quantitated in non-inflamed keratoacanthoma (KA), inflamed KA, non-inflamed squamous cell carcinoma (SCC), and inflamed SCC, by their content of S100 protein. The number of LCs per high-power field was markedly increased in inflamed KA when compared to the other groups. Using similar methods on frozen sections, the expression of HLA-DR was identified on keratinocytes in KA in areas of inflammation but not in other lesions under study. We hypothesize that increased numbers of LCs in inflamed KA are part of the process which results in tumor regression.
We have identified a monoclonal antibody (ERY-1), which reacts with erythrocytes, erythroid precursor cells, and with embryonal yolk sac, and normal liver and kidney. The antibody also decorates the neoplastic cells of hepatocellular, renal, and yolk sac carcinomas. No reactivity was seen in a variety of other epithelial or mesenchymal neoplasms. It is possible that ERY-1 recognizes an erythropoiesis-associated antigen present in yolk sac, kidney, liver, and bone marrow, all of which are involved in erythropoiesis in various stages of human development. Furthermore, ERY-1 has proved to be extremely useful in the histopathologic diagnosis of hepatocellular and renal cell carcinomas.
BALB/c mice were exposed simultaneously to three nonrelated immunogens, myelin basic protein, uridyl-galactosyl transferase, and tissue obtained from a formalin-fixed, paraffin-embedded block containing a pilomatrixoma. Standard hybridoma techniques were used and antibody generation assayed using an unlabelled antibody biotin-avidin method with sections of human cerebellum, liver, and pilomatrixoma as the substrates. Using the above assay, clones were selected that secreted antibodies with selective specificities for each of the immunogens. By ELISA assay, the monoclonal antibodies reacting with cerebellum also reacted to the myelin basic protein preparation used as immunogen and the monoclonal antibody reacting to hepatocytes bound to the preparation of uridyl-galactosyl transferase used as immunogen. Our data suggests that the generation of monoclonal antibodies with a variety of diagnostic applications can be obtained from a single fusion following immunization with multiple nonrelated antigens, requiring considerably less laboratory cost and effort than would be required to obtain similar monoclonal antibodies in separate fusions.
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Twenty mucinous cystadenocarcinomas of the pancreas, most of which occurred in the tail of the pancreas in middle-aged women, were examined histologically and by immunohistochemical stains. Thirteen tumors displayed a marked histological heterogeneity and expressed intestinal differentiation as shown by the colonic appearance of the glands both at the light- and electron-microscopic levels. Other intestinal features included varying numbers of goblet cells, argyrophil and argentaffin cells, and even Paneth cells. By immunohistochemistry, endocrine cells were present in 13 of the 20 tumors (65%) and were more numerous in the poorly differentiated than in the well-differentiated epithelial component of the tumors. Serotonin-containing cells were the most common endocrine cells, followed by somatostatin-containing cells and cells that showed immunoreactivity for pancreatic polypeptide and gastrin. However, none of the patients had clinical manifestations of carcinoid, somatostatinoma, or the Zollinger-Ellison syndrome. The findings support the hypothesis that mucinous cystadenocarcinomas of the pancreas arise from an "endodermal stem cell" that differentiates into cells with intestinal phenotypes.
The diagnosis of renal cell carcinoma was established by computed tomography-guided aspiration in two small solid lesions occurring in end-stage kidneys. This represents a safe means of providing more specific information about the various lesions that specific information about the various lesions that frequently develop in chronic hemodialysis patients: complex cysts, adenoma, and renal cell carcinoma. The proposed conservative approach of simple observation of these lesions may be altered if a precise diagnosis is obtained. Computed tomography is considered the most reliable imaging modality for evaluation and guided aspiration.
The morphologic spectrum of intestinal metaplasia was studied in 49 gallbladders that had been excised because of cholelithiasis. Based on the absence or presence of endocrine cells, the cases of intestinal metaplasia were arbitrarily divided into two groups. The gallbladders from the first group (26 cases) contained isolated or small clusters of mature goblet cells, while those from the second group (23 cases), in addition to the goblet cells, contained argyrophil and argentaffin cells and, less frequently, Paneth cells and gland-like structures similar to colonic crypts. Pseudopyloric glands and superficial gastric-type epithelium were present in both groups. Argyrophil cells outnumbered argentaffin cells by a ratio of 4 to 1. By immunocytochemical methods serotonin-containing cells were found to be the most common endocrine cells. Other endocrine cells showed immunoreactivity for somatostatin, cholecystokinin, gastrin, and pancreatic polypeptide. The presence of gut endocrine cells and Paneth cells in the pseudopyloric glands suggests that these glands are also an integral component of intestinal metaplasia of the gallbladder. The findings support the hypothesis that cholelithiasis induces the appearance of a stem endodermal cell that, in turn, may differentiate into cells with mature intestinal or gastric phenotypes.
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Seven examples of a distinctive morphological variant of well-differentiated adenocarcinoma of the gallbladder with intestinal features are reported. Four tumors were composed predominantly of goblet cells and absorptive columnar cells, two of which had, in addition, a few Paneth cells and neuroendocrine cells. Three neoplasms closely resembled colonic carcinoma, and one of these also contained neuroendocrine cells. Serotonin-immunoreactive cells were demonstrated in three of the seven intestinal-type adenocarcinomas, two of which also had cells that stained for somatostatin pancreatic polypeptide and cholecystokinin. Four adenocarcinomas were associated with cholelithiasis, and three with intestinal metaplasia of the uninvolved mucosa. Despite the well-differentiated character of all neoplasms and the deceptively benign microscopic appearance of two of them, three patients died with extension to the liver and metastasis. Of the two survivors, one had carcinoma in situ and the other had a carcinoma that extended only to the muscle layer of the gallbladder. The various cell phenotypes found in these gallbladder adenocarcinomas can be explained on the basis of intestinal differentiation.
Skin and thymus were obtained from abortuses of varying ages and from neonatal autopsies to determine if S100-protein-containing dendritic cells were present. Using an unlabeled antibody peroxidase-antiperoxidase method, we could not detect these dendritic cells in epidermis prior to live birth, but did detect them at all fetal ages in thymus. Within 24 hours of live, full-term delivery, dendritic cells containing S100 protein were identified in epidermis.
Using specific antibodies and the peroxidase-antiperoxidase technique, we were able to demonstrate a variety of fungal organisms in smears and sections of formaldehyde-fixed, paraffin-embedded tissue. The procedure is simple, fast, and accurate and may be used as an alternative to, or in conjunction with, cultural methods to identify fungi specifically.
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