Chromogranin A, neuron-specific enolase and synaptophysin as neuroendocrine cell markers in the diagnosis of tumours of the gastro-entero-pancreatic system.

Neuroendocrine (NE) tumours of the gastro-entero-pancreatic tract were analysed immunohistochemically for the expression of chromogranin A, neuron-specific enolase and synaptophysin. In all cases at least one marker was present and in 17 out of 19 investigated neoplasms, at least one of the three markers could be demonstrated in more than 75% of the NE tumour cells. Monoclonal antibody chromogranin A stained a much higher proportion of NE cells in tumours with hormonal activity than in hormonally inactive ones. Immunostaining of the primary tumour as compared to its respective metastases was almost identical. Thus, chromogranin A, neuron-specific enolase and synaptophysin identify NE tumours and their metastases regardless of their localization and their state of hormonal activity. As 'panendocrine' markers of NE tumours they are of special diagnostic value in NE tumours that do not produce hormones and peptides.

[Comparative study of the content of 1,25-dihydroxyvitamin D3 receptors in digestive mucosa and adenocarcinoma]. / Etude comparative du contenu en récepteurs de la 1,25-dihydroxyvitamine D3 dans des muqueuses et des adénocarcinomes digestifs.

We have studied and compared the 1,25-dihydroxyvitamin D3 receptor (RD3) content of 154 human digestive carcinoma with the normal mucosa one, removed at distance from the same surgical specimen. The distribution of biopsies is as follows: 5 oesophagus, 10 stomach, 6 small bowel, 35 right colon, 47 left colon, 40 rectum and 11 pancreas. RD3 were measured by the Dextran Coated Charcoal method and characterized by sucrose gradient ultracentrifugation. One single class of high affinity binding sites (kD = 1.5 +/- 0.7 x 10(-10) M) was defined, with a sedimentation coefficient of approximately 3.4 S. The RD3 was present in the 6 samples of small bowel and in 82% of whole normal mucosa, whatever their localization along the digestive tract and pancreas, while in the tumoral tissue, the RD3 was positive in only 32% of the cases. In these tumor specimens the incidence decreases from 64% in the right colon to 27% in the left colon and only 15% in the rectum (P less than 0.001). RD3 rates vary slightly with the localization and are of the same level in normal tissues and in tumors: 10-314 (median = 59) vs 13-175 (median = 64) (P greater than 0.005) respectively. No significative variations relating to age or sex of patients were found. However, all RD3 positive tumors from left colon and rectum were well differentiated histologically. These results show that the normal colonic mucosa is a potential target for 1,25-dihydroxyvitamin D3, which can play a role in the metabolism of calcium and other ions. They also suggest that vitamin D3 could be a modulator of colorectal cell growth and differentiation and its receptor is frequently lost during malignant transformation.

UCHL1-positive extranodal lymphoma resembling multiple lymphomatous polyposis of the gastrointestinal tract.

Histopathologic and immunohistochemical studies were done on paraffin sections from a patient with alimentary tract lymphoma resembling multiple lymphomatous polyposis of the gastrointestinal tract (MLP). Diffuse, but not follicular, proliferation of medium-sized lymphoid cells was noted in the polypoid lesions of the alimentary tract, peripancreatic lymph nodes, spleen, liver, and bone marrow. These cells possessed a T-cell-related antigen (UCHL1), but were negative for the B-cell-related and myeloid cell-related antigens examined. Because neoplastic cells in MLP are usually of B-cell origin, the current case will provide important information on the relation between phenotypes and morphologic patterns of proliferation.

Presence of dopamine D-2 receptors in human tumoral cell lines.

[125I] Iodosulpride binding was examined on eight human cell lines derived from lung, breast and digestive tract carcinomas, neuroblastomas and leukemia. Specific binding was detected in five of these cell lines. In the richest cell line N417, derived from small cell lung carcinoma, [125I] iodosulpride bound with a high affinity (Kd = 1.3 nM) to an apparently homogeneous population of binding site (Bmax = 1,606 sites per cell). These sites displayed a typical D-2 specificity, established with several dopaminergic agonists and antagonists selective of either D-1 or D-2 receptor subtypes. In addition, dopamine, apomorphine and RU 24926 distinguished high- and low-affinity sites, suggesting that the binding sites are associated with a G-protein. The biological significance and the possible diagnostic implication of the presence of D-2 receptors on these cell lines are discussed.

Gastrointestinal stromal tumors. An immunohistochemical study of cellular differentiation.

Forty-five benign and 11 malignant gastrointestinal stromal tumors (GIST) were immunohistochemically studied for the presence of desmin, muscle actins (MA) and S-100 protein. To facilitate the analysis, the tumors were divided into four groups by light microscopy: (1) typical leiomyomas comparable to peripheral leiomyomas (n = 9); (2) cellular spindle cell tumors (n = 29); (3) round cell tumors ("leiomyoblastomas" n = 7); and (4) sarcomas (n = 11). The typical leiomyomas were desmin- and MA-positive throughout, and showed well-differentiated smooth muscle cells by electron microscopy, similar to the normal gastric smooth muscle cells. All esophageal leiomyomas belonged to this group. Nineteen of 29 of the Group 2 tumors showed desmin positivity and 20 of 29 showed MA positivity, but usually only in less than 10% of the tumor cells, and in many instances it was very difficult to determine whether the positive cells were real tumor cells or entrapped muscle cells. Only 5 of 29 of Group 2 tumors showed widespread desmin positivity and 11 of 29 showed similar MA positivity. Of round cell tumors, only 1 of 7 showed desmin-positive cells and 3 of 7 MA-positive cells. None of the sarcomas showed desmin, while MA positivity was found in 6 of 11 cases, often in a large number of tumor cells. Seven tumors showed a significant number of S-100 positive tumor cells, but four of these also showed a high number of desmin- and MA-positive cells, suggesting that these tumors represented complex proliferations of muscle and Schwann cell elements. Two purely S-100 positive benign probably Schwann cell-like tumors were found, both in the small bowel. Small number of S-100 positive cells were commonly found in GIST, and these probably represented entrapped Schwann cells, because many tumors showed simultaneous proliferation of non-neoplastic nerves.

Concentration and localization of carbohydrate antigen 19-9 in tissues of pancreatic cancer.

Carbohydrate antigen (CA) 19-9 concentration in the tissue-extracts of cancerous and noncancerous pancreatic tissues were determined by radioimmunoassay. Pancreatic cancer tissues revealed significantly elevated CA 19-9 concentrations, when compared with chronic pancreatitis, normal adult pancreas, or fetal pancreas tissues. Metastatic liver tumors from pancreatic cancer also showed extremely high CA 19-9 concentrations, and there was no significant correlation between tissue CA 19-9 concentration and serum CA 19-9 level in patients with pancreatic cancer. In addition, positive localization of CA 19-9 was clearly observed in cancer cells of pancreatic cancerous tissues by immunohistochemical study, confirming the remarkable increase of CA 19-9 concentration in tissues of pancreatic cancer, although CA 19-9 was also partially found in non-malignant pancreatic tissues. The results indicated that CA 19-9 would be produced in great quantities by cancer cells in tissues of pancreatic cancer, and thus could be a valuable tumor associated antigen suggesting its clinical use as a tumor marker for cancer of the pancreas.

Transcriptional organization of bovine papillomavirus type 4.

Seven virus-specific RNA transcripts have been identified in tumours induced by bovine papillomavirus type 4 (BPV-4). The RNAs measured 4.2, 3.6, 3.0, 2.8, 1.9, 1.6 and 1.0 kilobases (kb). They were mapped on the viral genome by Northern blot hybridization to subgenomic probes, by cDNA hybridization to viral DNA fragments and by S1 analysis of unlabelled and 3' and 5' end-labelled DNA fragments. All the RNA species are transcribed from the same DNA strand, are polyadenylated and with the exception of the 1.0 kb RNA internally spliced. The 3.0, 1.9, 1.6 and 1.0 kb RNAs share the same 3' polyadenylation site at nucleotide 4009 whereas the 4.2 kb RNA and the 2.8 kb RNAs terminate near a polyadenylation site at nucleotide 7187. The 4.2 kb and the 2.8 kb RNAs are transcribed from the late open reading frames and encode the structural polypeptides; the 3.0, 1.9, 1.6 and 1.0 kb RNAs are transcribed from the early open reading frames and are the transcripts involved in viral replication and cellular transformation.

Complex cytokeratin polypeptide patterns observed in certain human carcinomas.

Human epithelial cells contain, intermediate-sized filaments formed by polypeptides related to epidermal alpha-keratin ("cytokeratins") which are expressed in different combinations in different epithelia. Using cytoskeletal proteins from human biopsies and autopsies we have examined, by two-dimensional gel electrophoresis and immunoblotting experiments, the cytokeratin polypeptide patterns of diverse primary and metastatic carcinomas and have compared them with those of corresponding normal epithelial tissues and cultured cells. Five groups of carcinoma cytokeratin patterns can be discriminated. (1) Cytokeratins typical of simple epithelia (polypeptides Nos. 7, 8, 18, 19) are expressed, in various combinations, by many adenocarcinomas, for example those of gastrointestinal tract. (2) Cytokeratins typical of stratified epithelia (Nos. 1, 5, 6, 10, 11, 14-17) are found, in various combinations, in squamous cell carcinomas of skin and tongue. (3) Complex patterns showing polypeptides Nos. 7, 8, 18, 19, and one basic component (No. 5 or 6) are detected in certain carcinomas of the respiratory tract and the breast. (4) Complex patterns containing cytokeratins widespread in stratified epithelia (Nos. 4-6, 14-17) as well as components Nos. 8 and 19 occur in diverse squamous cell carcinomas derived from non-cornified stratified epithelia, with or without additional small amounts of cytokeratin No. 18. (5) Patterns of unusually high complexity can be found in some rare tumors as is shown for a cloacogenic carcinoma. No significant qualitative changes of expression of cytokeratins were found when primary tumors and metastases were compared. When compared with cytokeratin patterns of normal epithelia, carcinomas of the first type usually display a high degree of relatedness to the tissue of origin. Other carcinomas do not express some of the cytokeratins present in the tissue of their origin and, vice versa, certain components which are minor or apparently absent in normal tissue are major cytokeratins in the corresponding tumor. These differences may be explained by cell type selection during carcinogenesis, but changes of expression during tumor development cannot be categorically excluded. The possibility of cell type heterogeneity within a given tumor is also discussed. Similarly complex patterns of cytokeratin polypeptides have been noted in certain cultured human carcinoma cell lines (e.g., A-431, RPMI 2650, Detroit 562, A-549) and can also be observed in cell clones. The possible value of analyses of cytokeratin patterns, by gel electrophoresis or specific monoclonal antibodies, in distinguishing different carcinomas by non-morphologic criteria is discussed.