Lymphoid proliferations and lymphomas associated with gastric metaplasia, dysplasia, and carcinoma.

Gastric carcinomas are invariably accompanied by lymphoid proliferations. We studied their features in 22 resected gastric carcinomas in which the lymphoid proliferations ranged from reactive lymphoid follicles to mucosa-associated lymphoid tissue (MALT) lymphomas. In most cases, the collections of lymphocytes were abundant, which is remarkable considering the lack of lymphoid tissue in the normal stomach. They were not haphazardly located but in direct contact with the metaplastic, dysplastic, and neoplastic epithelial cells, in positions suggestive of defense barriers. They consisted of newly formed lymphoid follicles with reactive germinal centers sometimes high up in the superficial mucosa, collections of plasma cells beneath the surface epithelium, and large aggregates of B cells above and below the muscularis mucosae as well as abundant T cells. The latter, both CD4+ and CD8+, were seen within metaplastic epithelial cells as well as within carcinomatous glands that were partially destroyed, resembling apparent neoplastic lympho-epithelial lesions (LEL). In three cases, the B cells infiltrating the gastric muscular layers represented MALT-lymphomas adjacent to gastric carcinomas, as confirmed by polymerase chain reaction (PCR) analysis in two cases. In a case of lymphoepithelioma-like carcinoma, the excessive lymphoid cells were predominantly of T-CD8+ type. In this case, EBV identified by EBV-encoded RNA and latent membrane protein was present in large amounts. Helicobacter pylori was seen in only six cases in areas of chronic gastritis that were distant from carcinoma. H. pylori was not present in the areas of metaplasia, dysplasia, or carcinoma. It appears that the lymphoid proliferations accompanying these gastric changes do not arise in response to the pathogenic agent H. pylori, which caused the persistent infection leading to them yet is no longer present, but rather in response to the existence of the abnormal epithelial cells. Thus the lymphoid proliferations consistently associated with gastric metaplasia, dysplasia, and neoplasia may be regarded as immune reactions to the long-term cellular changes triggered by the initial chronic gastritis. On rare occasions, the exaggerated lymphoid proliferations may reach the end of the spectrum, resulting in MALT lymphomas coexistent with gastric carcinomas.

Lymphoid monoclonal antibodies reactive with lung tumors. Diagnostic applications.

In the course of investigating 30 monoclonal antibodies (MAbs) for their potential reactivity with 25 lung tumors of different histologic types, we found that three MAbs commonly used for their specificities for lymphoid markers were highly reactive with non-small-cell carcinomas (NSCLC) and totally nonreactive with small-cell carcinomas (SCLC). Immunostaining was performed by the standard streptavidin-biotin-peroxidase method after microwave antigen retrieval on formalin-fixed, paraffin-embedded tissue sections. LN2 (CD74), LN3 (HLA-DR), and BLA-36, which are commonly used for the identification of B-lymphocytes, strongly immunostained 19 of 25 squamous and adenocarcinomas and none of 34 small-cell carcinomas and carcinoids. Moreover, in combined tumors, these MAbs selectively stained the adenocarcinoma cells but not the adjacent small-cell carcinoma cells. A cocktail mixture of LN2, LN3, and BLA-36 assayed on 24 additional lung tumors produced similar results with even stronger and sharper stainings. Other lymphoid MAbs showed some selective staining but to a lesser degree. Among nonlymphoid MAbs, the results were as expected, with MAbs for cytokeratin (B72.3) and epithelial membrane antigen staining NSCLC but also some SCLC. The MAbs for chromogranin and neuron-specific enolase were not entirely specific, whereas some nerve-cell adhesion molecule MAbs showed good specificity for SCLC. In a field with few specific MAbs, the newly discovered ability of these lymphoid MAbs to discriminate between SCLC and NSCLC may prove useful in the immunohistochemical diagnosis of lung tumors.

Kaposi's sarcoma of internal organs. A multiparameter study of 86 cases.

BACKGROUND: During the past decade, Kaposi's sarcoma (KS), one of the most common acquired immune deficiency syndrome-defining diseases, has been the subject of sustained research. However, basic questions about its etiology, histogenesis, growth, and dissemination remain unanswered. Even its nature, whether hyperplasia or neoplasia, is still controversial. Most studies and concepts to date have been based on dermatologic KS. The present study, in contrast, examines by various parameters a series of patients with KS of internal organs. MATERIALS AND METHODS: The series includes 86 cases (39 surgical specimens and 47 autopsies) of visceral and disseminated KS. The study is focused on the gross distribution of lesions, the mode of dissemination, the histologic patterns, and the cellular immunophenotypes, which are investigated with the use of 18 monoclonal antibodies. RESULTS: The involvement of various organs, multiplicity of lesions, and progression of tumors were recorded. Seven histologic patterns forming a spectrum of cellular differentiation were distinguished. Immunophenotypes characteristic for different histologic patterns were recognized. Although some cell markers such as those recognized by antibodies against Factor VIII R-Ag, Actin, and Ulex europaeus were restricted to the well differentiated KS cells, others including CD34 and CD31 demonstrated a strong affinity for the entire spectrum of KS cell differentiation. CONCLUSION: The present study of KS of internal organs revealed that poor grades of histologic and immunophenotypic differentiation correlated with invasion and dissemination, which are fundamental characteristics of malignant tumors.

Ovarian cancer-associated antibodies recovered from ascites: their use for the isolation of ovarian cancer-associated antigen to produce monoclonal antibodies.

Immune complexes (ICs) were recovered from the ascites of a patient with stage IV endometrioid ovarian cancer by sequential precipitation with 33% saturated ammonium sulfate and 2.5% polyethylene glycol 6000 (PEG 6000), followed by affinity chromatography on protein A-Sepharose CL-4B. The IgG-containing ICs were dissociated using 8 M urea, separated by ion-exchange chromatography on Sephadex QAE-50, and subsequently analyzed for purity by immunoelectrophoresis (IEP) and radial immunodiffusion (RID). Recovered antibody was tested for reactivity by immunohistologic techniques against paraffin-embedded tumor tissue and acetone-fixed cell suspensions of epithelial tumors. The antibody which demonstrated ovarian cancer-associated activity was absorbed with antigen extracts of breast, colon, and lung cancers as well as keratin to reduce cross-reactivity. The absorbed endometrioid ovarian cancer-associated antibody (OCAAb) was used to produce an immunoadsorbent column for the recovery of tumor-associated antigens. A mouse monoclonal antibody designated FEN-1 was produced using this antigen-containing fraction, and preliminary screening has demonstrated ovarian tumor-associated reactivity. The use of autologous ICs as reagents for preparing tumor antigen-rich immunogens may provide a valuable tool in the search for tumor-associated antigens.

Immunohistochemical characterization of a monoclonal antibody detecting an endometrioid ovarian cancer-associated antigen.

Murine monoclonal antibody FEN-1 was derived by immunizing Balb/c mice with an affinity-purified endometrioid ovarian cancer-associated antigen recovered from ascites-derived immune complexes. Splenic lymphocytes from the immunized mouse were fused with the myeloma cells SP2/0-AG14 in the presence of PEG 1500. The hybrid cultures were screened for production of immunoglobulins reactive with an extract preparation of an endometrioid ovarian tumor by enzyme-linked immunosorbent assay and flow cytometry. One of the hybrids secretes a monoclonal antibody of the IgG3 subtype designated FEN-1, which reacts with 100% of endometrioid ovarian cancer containing adenoacanthoma by indirect immunoperoxidase on paraffin-embedded tissue. No detectable levels of antigen were found in squamous metaplasia associated with nonendometrioid tumors, and no reactivity occurred against endometrial adenocarcinomas, endometriosis, or normal ovary and endometrium. The antibody does not cross-react with mucinous tumors, nonepithelial tumors of the ovary, or gastrointestinal tissue. This antibody may be used as an aid in the diagnosis of nonmucinous ovarian carcinomas by immunohistology.

Description of an endometrioid ovarian cancer cell line.

A human cell line, designated L-1, has been established from the ascites of an untreated patient with stage IV (FIGO) endometrioid ovarian cancer. This cell line initially grew uninterupted for 6 months without fibroblast contamination and contact inhibition, and has been subcultured weekly for the past 7 years. L-1 does not contain steroid hormone receptors nor does it demonstrate the presence of oncofetal antigens by immunohistochemical techniques. The doubling time of L-1 is 11.8 hr. Flow cytometric analysis reveals an aneuploid DNA peak, and an abnormal karyotype demonstrates hyperdiploidy, translocations, and deletions. Morphology, growth patterns, cytogenetic analysis, and other features of L-1 are characterized.