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The prevalence of Campylobacter pylori (CP) in gastric biopsies from cancer patients has not been previously studied. We reviewed 112 gastric biopsies from 78 adult patients at a cancer hospital. The patients had a previous history or current diagnosis of gastric or esophageal carcinoma (26 patients), gastric lymphoma (15 patients), gastric stromal tumor (three patients), carcinoid tumor (two patients), nongastroesophageal malignancy (29 patients), or atrophic gastritis with nonhealing ulcer (three patients). The biopsies were stained with hematoxylin-eosin (H&E), Warthin-Starry, Giemsa, and Brown-Hopps. CP was identified in 30 biopsies from 26 patients. Eighteen of the biopsies showed active gastritis, nine showed chronic inflammation/intestinal metaplasia, and one contained an ulcer. CP was also identified in two stomachs bearing tumors (one adenocarcinoma, one carcinoid tumor). Active gastritis was present without CP in nine biopsies, including three from patients on chemotherapy and one from a patient with bile reflux. The organism was detected by the Warthin-Starry stain in 30 biopsies. The Giemsa stain was positive in 27, Brown-Hopps in 27, and H&E in 24. Non-CP bacteria were identified in the Brown-Hopps in seven cases and were mistaken for CP in H&E stains in two. We conclude that CP is frequently found in the cancer patient with active gastritis and is an occasional finding in tumor-bearing stomachs. Special stains are useful in identifying CP, and the Brown-Hopps is helpful in distinguishing CP from other bacteria.

Basal cell hyperplasia of the prostate is a rare, benign lesion that often has been misdiagnosed as adenocarcinoma. Thirteen cases of basal cell hyperplasia were reviewed. All of the patients were over 60 years of age (range 63-83) and all had benign prostatic hypertrophy in addition to basal cell hyperplasia. Histologic features consisted of nests of uniform small cells with scant cytoplasm forming solid nests and acinar structures. Some foci had nodular configurations and most were located within larger nodules of "typical" glandular hyperplasia. In some instances there was a merging of the two types of hyperplasia. There was neither nuclear atypia nor pleomorphism, and the adjacent stroma was hyperplastic. Small elongated cells with desmosomes and nonspecific, dense bodies were seen on electron microscopic studies of formalin-fixed material. The architectural and cytologic features of the basal cell proliferations were not those of carcinoma. However, synchronously, two patients demonstrated foci of prostate carcinoma unrelated to the basal cell hyperplasia.

Carcinomas involving the jejunum and ileum are rare tumors. During a review of small intestinal neoplasms, six primary carcinomas of jejunum or ileum with an anaplastic and sarcomatoid histology were identified. At presentation, three of the patients had symptoms related to metastatic disease and three had symptoms referable to the local tumor. The tumors were large (greater than 4.5 cm in diameter), usually endophytic masses composed of large cells with eosinophilic cytoplasm, anaplastic nuclei, and prominent nucleoli. In many areas, the cells had a spindled configuration. Mucin positivity was identified in all six cases. Electron microscopic findings in two cases were indicative of epithelial differentiation. The tumors behaved aggressively; all five patients for whom there was clinical follow-up died of metastases within 40 months. The six anaplastic and sarcomatoid carcinomas were compared with 29 typical adenocarcinomas arising in the jejunum or ileum. Only two of the latter group had symptoms referable to distant metastases at presentation. These tumors also tended to be smaller at presentation (11 tumors were less than 4 cm in greatest dimension). Of 25 patients with typical adenocarcinomas who had acceptable follow-up, 18 (72%) died of disease and five (20%) were alive with no evidence of disease after 5 years. We conclude that anaplastic and sarcomatoid carcinoma is a rare variant of small intestinal carcinoma with an aggressive clinical course.

To determine if the amount of chondroitin sulfate proteoglycan (CSPG) in human colorectal tumor tissue correlates with the tumor's aggressiveness we immunochemically determined the CSPG levels in colorectal carcinomas at different stages. A total of 50 specimens--4 polyps, 15 stage B tumors, 9 stage C tumors, 12 stage D tumors, 7 liver metastases, and 3 lymph node metastases--were examined. Tumor tissues were extracted with 4 M guanidine hydrochloride containing protease inhibitors. The extracts were serially diluted and blotted onto nitrocellulose membranes. Reactivity of a chondroitin sulfate-specific mouse monoclonal antibody (CS-56) was determined by biotinylated goat antimouse Ig and avidin-biotin-peroxidase complex. After comparing tissues from tumors at different stages (classified by the presence or absence of metastasis), we could not find a positive or negative correlation between the amount of CSPG in primary colorectal carcinoma tissues and the tumor's metastatic potential. However, the metastatic foci in the liver or lymph node contained higher amounts of CSPG than the primary tumors did. Immunohistochemical staining of colon carcinoma tissue with CS-56 revealed that CSPG is predominantly localized in fibrotic portions in the tumor tissues. Two-year follow-up studies indicated that a high level of CSPG in primary tumors was not predictive of recurrence.

We collected a total of 78 tissue specimens, including primary colorectal carcinoma, normal colonic mucosa, and liver metastases of colon carcinoma, to examine whether the extracts of these tissues inhibited the binding of a monoclonal antibody FH6, specific for sialyl-dimeric LeX antigen. The results of inhibition assays demonstrated that: (a) contents of FH6-reactive molecules were greater in carcinoma tissues than in normal colonic mucosa; (b) metastatic foci in livers contained more FH6-reactive molecules than primary tumors; (c) primary tumors from Dukes' stage B1 patients contained less FH6-reactive molecules than primary tumors from Dukes' stage D patients. The inhibitory activity of these tumor tissue extracts against the binding of a monoclonal antibody FH6 to cultured colon carcinoma cells was eliminated by prior treatment of the extracts with sialidase, confirming that the FH6-reactive materials were sialyl-dimeric LeX antigen. Electrophoretic separation of tumor tissue extracts on 3% polyacrylamide gels followed by direct staining with monoclonal antibody FH6 revealed that very high molecular weight glycoproteins, presumably mucins, contained sialyl-dimeric LeX antigen.

Electron microscopy can be of limited value in distinguishing among poorly differentiated hepatocellular carcinomas, bile duct carcinomas, and other adenocarcinomas, but may be very helpful in identifying tumors that are metastatic to the liver. The characteristic ultrastructural features of endocrine and exocrine tumors of the pancreas are readily distinguished by electron microscopy when the tissue is adequately preserved, and this technique can be very useful in establishing a diagnosis.

The condition of a 6-year-old boy was diagnosed as mixed-cellularity Hodgkin's disease that involved the right side of the neck. Five years after the completion of radiation therapy for the involved area, followed by six courses of chemotherapy with mechlorethamine hydrochloride (nitrogen mustard), vincristine sulfate, procarbazine hydrochloride, and prednisone, he developed cerebral gliosarcoma. Numerous second malignant neoplasms have been reported in adults following treatment for Hodgkin's disease; however, the sequence of events in our patient is a new finding that has not, to our knowledge, been reported previously. While the second malignant tumor may have been induced by prior treatment, direct evidence is lacking.

Antibodies to specific human immunodeficiency virus (HIV) polypeptides are important laboratory markers of HIV infection. We have used an antibody to the major structural gag protein p24 of HIV-1 virus to immunochemically localize this capsid antigen in lymphoid cells from seven of eight patients at risk for HIV infection and who presented with parotid lymphadenopathy and lymphoepithelial cysts of the parotid gland. A clinicopathological assessment of these two manifestations as they relate to HIV infection is also presented.

To determine whether the production of experimental hepatic metastases in athymic nude mice by human colorectal carcinomas (HCC) correlated with the clinical outcome in patients, we harvested colorectal carcinomas from 82 patients, dissociated the tumors with collagenase and DNase, and injected them into groups of nude mice, either in the flank to assess experimental tumorigenicity or into the spleen to produce experimental metastasis in the liver. Growth in mice was then associated with clinicopathological factors and clinical outcome. Growth of HCC in either the flanks or the livers of nude mice was associated with the time to recurrence in a Wilcoxon analysis. Analysis of the outcome data in a Cox proportional hazards model suggested that there was an interaction between tumorigenicity and metastatic potential of HCC in nude mice and serum CEA concentration in the patient and stage of disease. A univariate analysis indicated that both tumorigenicity and metastatic potential of HCC in nude mice were significantly associated with the serum CEA concentration of the patient but not with the other variables of stage of disease, mucin production, local tissue invasion, state of differentiation, or sex. A subset of 57 patients was operated upon for cure and followed prospectively for up to 61 months. Tumorigenicity and, to a lesser extent, experimental metastatic potential were associated with disease recurrence in 23 of these patients. Seventy-eight % of the subset of patients who were operated upon for cure developed liver metastasis as one site of their progressive disease. Thus, the ability of HCC cells isolated from surgical specimens to grow in athymic nude mice correlates with the development of advanced disease in patients.

A 29-yr-old woman developed severe, progressive cholestasis 5 months after allogeneic bone marrow transplantation. Extrahepatic graft-versus-host disease (GVHD) was absent. Skin biopsy was equivocal 2 months after transplant, rash was absent during the period of cholestasis, and cholangiographic abnormalities were absent. Liver biopsy 7.5 months posttransplant revealed chronic hepatic GVHD. Cholestasis dramatically resolved with high dose corticosteroid therapy. Chronic hepatic GVHD occurs in the absence of overt extraintestinal GVHD and respond promptly to therapy. This underscores the importance of aggressive diagnostic evaluation of posttransplant cholestasis.

The antibody response of patients was used to characterize the autoantigens in human colorectal carcinoma. Twenty-seven primary and 13 metastatic carcinomas with paired normal tissues were extracted and transferred onto nitrocellulose membranes by the Western transfer technique. After the transfers were incubated with the serum of the patient from whom the tumor was derived, autoantigens were identified by indirect immunoperoxidase staining. All tumors contained at least one autoantigen. Six tumor-associated autoantigens, ranging in molecular weight from 26 to 58 kilodaltons (kD), were identified by antibodies in 25% or more of the sera. Eleven metastases expressed a 41-kD autoantigen that was present in only a third of the extracts of normal liver or lung. Thus, the number of dominant polypeptide autoantigens in colorectal carcinoma is restricted to six molecules. These autoantigens may be organ-associated antigens that are expressed by neoplastic cells. The 41-kD autoantigen may be a potential marker for metastases. A generic vaccine appears to be feasible for colorectal carcinoma since the number of dominant antigens is limited.

A Ulex europeus agglutinin I (UEAI)-reactive glycoprotein(s) with molecular weight higher than 300,000 was detected by direct binding of 125I-labeled UEAI to lysates of rectal or sigmoid colon cancer tissues separated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. This was the major UEAI-reactive molecule in tumor tissues and different tumors possessed varying reactivities. Very little UEAI binding was detected to lower molecular weight components. Histochemical localization of UEAI confirmed that the UEAI-reactive molecules were mostly localized to the surface of carcinoma cells. A total of 135 fresh tissue samples, including those from adenocarcinoma, villous adenoma, and normal mucosa in surgical specimens (69 patients), were examined to determine the reactivities of UEAI to the high molecular weight component in the tissue extracts. The quantitative binding of 125I-UEAI was compared according to the stage of colorectal cancer at the time of surgery. The relative amount of UEAI-reactive high molecular weight substance was significantly higher in the carcinomas than in normal mucosa. UEAI binding to high molecular weight regions of the polyacrylamide gel was significantly lower in primary colorectal adenocarcinomas from stage C or D patients than in those from stage B1 patients. Therefore, increased expression of the UEAI-reactive molecule was related to transformation of colorectal epithelial cells and decreased expression appeared to be associated with progression and metastatic potential.

Electron microscopy offers substantial aid in the diagnosis of gastrointestinal tract tumors, especially small-cell carcinoma and enterochromaffin-cell tumors. Tumors that are most difficult to classify by light microscopy--that is, poorly differentiated ones--may also have ultrastructural features by which the cell of origin can be determined. As always, the well-preserved tissue is more likely to retain diagnostic features than is the inadequately preserved.

Wheat germ agglutinin (WGA)-binding cellular glycoproteins produced by HT-29 human colon carcinoma and its variant cells established from liver metastases in nude mice after intrasplenic injection were analyzed by polyacrylamide gel electrophoresis. On 5.5% polyacrylamide gels five major sialoglycoproteins (approximate Mr 115,000, 145,000, 190,000, 450,000, and 740,000) reactive with WGA were common to the parental and metastatic sublines. There was an additional component of Mr approximately 900,000 that was prominent in cells established from liver metastases. Specific removal of sialic acid from the glycoproteins eliminated WGA binding, indicating that all the WGA-binding glycoproteins including the Mr 900,000 component were sialoglycoproteins. Smith degradation following mild acid hydrolysis resulted in formation of WGA-binding carbohydrate chains on Mr 115,000, 145,000, 190,000, and 900,000 components, but not on Mr 450,000 and 740,000 components, which indicated that these two sialoglycoproteins bore different oligosaccharides from the other sialoglycoproteins. The Mr 900,000 component was more prominent with HT-29 cells growing in nude mice than those growing in vitro. WGA binding to the Mr 900,000 component of metastasis-derived HT-29 cells growing in a nude mouse was higher than that of parental cells growing in nude mice. The expression in liver metastases derived from parental as well as metastatic cells was higher than the primary tumor growing in the spleen of the same mouse, indicating that the levels of Mr 900,000 sialoglycoprotein (SGP = 900) were regulated by intrinsic and environmental factors. The influence of organ microenvironmental factors was confirmed by analyzing sialoglycoproteins of HT-29 cells growing in the liver of a nude mouse following intrahepatic injection. Analyses of human colorectal carcinoma tissues and liver metastases revealed a polydisperse WGA-reactive high-molecular-weight component similar to that seen in tumors growing in nude mice. The mean value of WGA binding to high-molecular-weight glycoproteins in the primary tumors of stage B1 patients was smaller than that of all other primary tumors. Comparison of primary tumors with liver metastases from the same patients indicated that the level of SGP-900-like high-molecular-weight glycoproteins in metastases was not always higher than those in primary tumors.

Collagenolytic enzymes produced by tumor cells are believed to play a significant role in the destruction of surrounding normal tissue and, in certain experimental animal systems, the ability of tumor cells to degrade type-IV collagen (basement membrane collagen) correlates positively with those cells' metastatic capacity. We measured collagenolytic activity levels of extracts from freshly excised colorectal carcinoma tissues and of conditioned media from primary organ culture (total of 114 tissues from 53 patients) by using purified radiolabelled type-I (rat tail) and type-IV (mouse Engelbreth-Holm-Swarm [EHS] sarcoma) collagens. Both type-IV and type-I collagenolytic activity levels of extracts from tumor and adjacent mucosa ranged from less than 1 to 80 ng/hr/mg wet tissue, and no significant differences between mucosa and carcinoma tissues were observed. In conditioned media, the type-IV collagenolytic activity was low for normal mucosa and benign tumors and slightly higher for carcinoma than for mucosa. In 5 of 32 primary tumors, collagenolytic activity levels were 2-5 times higher than in the rest of the tumors and mucosal tissues. There were no significant differences in collagenolytic activity levels of conditioned media and tissue extract from colorectal carcinoma of different Dukes' stages. Deep and superficial areas of primary tumors released similar type-IV collagenolytic activity levels, suggesting that there was little intratumoral heterogeneity in the release of this enzyme.