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A series of monoclonal and polyclonal antibodies was used to determine the distribution of lymphocyte subsets in frozen tissue sections of a case of angiofollicular lymph node hyperplasia (ALNH), intermediate type. Primary follicles and mantle zones of secondary follicles consisted of BA1+OKIa1+-C3RTo5+sIgM+sIgD+ lymphocytes. Poorly developed follicular centers reacted with OKIa1, C3RTo5, DRC-1 and anti-IgM but contained no OKT4+Leu-3a+ or Leu-7+ cells. Mantle zones and primary follicles contained more OKT4+Leu-3a+ and less OKT8+ cells than normally observed. The interfollicular area consisted mainly of OKT4+Leu-3a+OKIa1- helper/inducer T-cells, admixed with some OKT8+ suppressor/cytotoxic T-cells and OKIa1+ interdigitating reticulum cells. Polyclonal plasma cells were found both in follicular centers and interfollicular areas. Based on the analogy to the peripheral lymphoid tissue in nude mice and in children with variable thymic dysfunction, it is suggested that the abnormal distribution of immunoregulatory T-cells may be of pathogenetic significance and may account for the morphology of the lymphoid follicles in ALNH.

A panel of previously characterized monoclonal antibodies: B67.6, OKT3, OKT4, B53.4, Leu3a, OKT8, Leu2a, OKM1, M12 and B52.1 were used as a probe to assess mononuclear cells in peripheral blood (PB), lymph nodes (LN) and spleens of untreated patients with Hodgkin's disease (HD). The mean % and absolute number of T lymphocytes were significantly decreased in PB of HD patients when compared with control values. Reduction of circulating T lymphocytes reflected the selective loss of cells showing the 'helper/inducer' ('H/I') phenotype. In fact, a lower number of these cells was demonstrated in HD patients with advanced disease and, even though to a lesser extent, in those with localized disease. In contrast, decreased values of T cells with the 'cytotoxic/suppressor' ('C/S') phenotype were only found in patients with advanced disease, showing pan-lymphocytopenia. Unlike PB, LN and spleens involved by HD usually showed increased %s of T lymphocytes, especially of those possessing the 'H/I' phenotype. The displacement of T lymphocytes with 'H/I' phenotype from PB to lymphoid organs further supports the possibility of a chronic immune response against abnormal cells or unknown antigens in the affected organs of patients with HD.

Immunoperoxidase staining incorporating an enzyme digestion step was performed on paraffin sections of 84 biopsy cases of lymphoproliferative disorders. Monoclonality was demonstrated in 100% of plasmacytomas and related tumours, and in 66% of non-Hodgkin's lymphomas. In 83% of lymphomas the immunoglobulin class was IgM and the light chain distribution was kappa 64% and lambda 36%. Polyclonality was found in 89% of cases of reactive lymphoid hyperplasia and within Reed-Sternberg cells in 55% of cases of Hodgkin's disease. Similar results were obtained by dispersed cell studies in 56 overlapping cases. The concordance rate between the two methods in 40 cases of non-Hodgkin's lymphoma was 67.5%. Reasons for the inconsistencies are discussed. Immunoperoxidase staining of enzyme digested paraffin sections is useful in the diagnosis of B cell lymphoproliferative disorders with a particular role in centres where cell suspension studies are not available or when there is no access to fresh tissue.

Using the sensitive peroxidase, anti-peroxidase immunohistological technique, carcinoembryonic antigen (CEA) was studied in formalin-fixed, paraffin-embedded cervical specimens from 225 patients. CEA was demonstrated in 33% of moderate dysplasia, 78.5% of severe dysplasia, 79% of in-situ carcinoma and 78% of invasive carcinoma. CEA was not demonstrated in normal squamous epithelium, squamous metaplasia, reserve cell hyperplasia nor in mild dysplasia.

The purpose of this paper is to review our current concept of the systems that subserve immunological functions. It concerns specifically the immunodeficiency diseases probably due to a B cell immunodeficiency. An attempt is made to classify those diseases clinically as well as roentgenologically. At last using the enteroclysis technique some examples of immunodeficiency syndromes are shown with special emphasis on developing a malignant disease.

In our previous studies acid cysteine-proteinase inhibitor (ACPI) was shown to be a common characteristic of human squamous epithelia and dendritic reticulum cells (DRC) in lymphoid secondary follicles. In the present study, the behaviour of ACPI-immunoreactive DRC in reactive lymphoid secondary follicles and neoplastic follicles of follicular-centre cell (FCC) lymphomas was compared by the peroxidase-antiperoxidase method. The secondary follicles in reactive lymphoid tissues revealed a staining pattern characteristic of DRC comparable with the results of other studies. Contrary to this, the number of ACPI-positive DRC in the neoplastic lymphoid follicles was greatly reduced. This was occasionally accompanied by a weak reaction and in many cases the DRC were totally abolished. Moreover, morphological aberrations were observed in ACPI-positive DRC, especially diminution and shortening of dendritic processes. On occasion, ACPI-positive cell types were observed, which may represent intermediate forms between DRC and fibroblastic reticulum cells. Only one case--with a rather favourable clinical outcome (out of 41 follicular FCC lymphomas) exhibited an ACPI-positive DRC pattern comparable with that of reactive lymphoid follicles. Thus it seems that the ACPI-immunohistochemistry of DRC provides an additional tool for discerning the difference between reactive and neoplastic lymphoid follicles. This method is of particular value since it can be used with formalin-fixed, paraffin-embedded tissues. There was a tendency among the follicular FCC lymphoma patients towards a better survival rate for those with ACPI-positive DRC than for those lacking this cell type, although no statistically significant differences emerged from this limited material.

An immunoperoxidase technique for the histological demonstration of Carcinoembryonic Antigen (CEA) was applied to paraffin sections from 74 breast carcinomas and 43 benign breast lesions. Sixty-six per cent of the carcinomas and the only case of granular cell myoblastoma examined were CEA positive. Two examples of mammary dysplasia (7%) showed foci of CEA positive acini. All tumour tissue found in lymphatics and in metastases in lymph nodes was CEA positive, including two cases where the primary tumour was CEA negative, and all the metastases examined from CEA positive tumours. A significant relationship was found between CEA positivity of the primary tumour and the presence of lymph node metastases.

The objective of this study was to demonstrate the diagnostic usefulness of flow cytometric analysis of surface membrane immunoglobulin light chain and monoclonal antibody reactivities in B cell non-Hodgkin's lymphoma. For this purpose, lymph node cell suspensions from 80 patients (20 normal lymph nodes, 11 lymph nodes with benign lymphoid hyperplasia, and 47 lymph nodes with B cell non-Hodgkin's lymphoma) were studied to detect the expression of surface B and T cell differentiation antigens recognized by a panel of monoclonal antibodies (anti-Leu-1, anti-Leu-5, anti-HLA-DR, J-5, anti-BL-1, anti-BL-2, and anti-BL-7). The clonal excess calculation, percent kappa-positive minus percent lambda-positive/percent kappa-positive plus percent lambda-positive cells per discrete level of fluorescence intensity, was used to study the clonality of surface membrane immunoglobulin light chain expression. Among the BL surface antigens, BL-7 proved to be most consistently expressed in B cell non-Hodgkin's lymphoma (79 percent). It was also present in 57 percent of lymph nodes with benign hyperplasia. No significant relationships were detected between the patterns of reactivity with the anti-BL monoclonal antibodies and histologic subtypes, although the small number of cases tested in each category precludes any definitive conclusions. Immunophenotypic heterogeneity within subgroups was also observed with expression of the other antigens examined. Monoclonal expression of surface membrane immunoglobulin light chain was seen in 43 of 47 (91 percent) of lymph nodes with non-Hodgkin's lymphoma, three of 11 (27 percent) hyperplastic lymph nodes, and one of 22 (4 percent) normal lymph nodes. When the presence of BL-7 and clonal excess was examined as a panel, 83 percent of B cell non-Hodgkin's lymphomas were positively identified, whereas one normal lymph node and no hyperplastic lymph nodes gave positive results. The simultaneous presence of clonal excess and BL-7 can be a useful diagnostic aid in the differentiation of lymphomatous from hyperplastic lymph nodes. Cytofluorimetry provides a rapid, objective, and reproducible technology to confirm the diagnosis of lymph node involvement in B cell non-Hodgkin's lymphoma.

Six oral squamous cell tumours classified as focal epithelial hyperplasia (FEH), Condyloma acuminatum (CA) and squamous cell papilloma (SQP) were subjected to indirect immunoperoxidase staining with anti-human papillomavirus (anti-HPV) antiserum to demonstrate the possible presence of HPV antigens in these lesions. The results are discussed in the light of the observations on HPV-lesions elsewhere in the body (in uterine cervix), and a suggestion is made to adopt the name condyloma for all those tumours where HPV aetiology can be established by ultrastructural or immunohistochemical means.

The immunocompetent cells (B and T lymphocytes, mononuclear phagocytes, MPS cells) known to be responsible for the rejection of the HPV- (Human Papillomavirus) induced tumors in the skin (warts) were analyzed in the infiltrates of 63 oral squamous cell lesions of suspected HPV origin (Condyloma, CA; Focal Epithelial Hyperplasia, FEH; Squamous Cell Papilloma, SQP) as well as in tumors thought to be unrelated to HPV (Fibrous Hyperplasia, FH; Papillary Hyperplasia, PH; True Fibroma, TF; Keratoacanthoma, KA), using the ANAE (acid alpha-naphthyl acetate esterase) technique. All tumors were also stained by the indirect immunoperoxidase-PAP method for the demonstration of HPV antigens. Of the SQP's, 60% were HPV-positive, as were 80% of CA's and one third of FEH's. In addition, 1/18 FH's and 2/14 PH's stained HPV-positive. On electron microscopy, viral particles could be disclosed within the nuclei of HPV-lesions. The highest proportions of the T and MPS cells (the elements of cell-mediated immunity) were found in CA's and SQP's (15-17%), as compared with the values of less than 10% in all others. The infiltrates in FEH's also showed low values of MPS and T cells, interpreted to suggest an etiology of the HPV type (determining the type of immune reaction) different from that of CA and SQP. HPV-positivity in the lesions did not influence the distribution of the immunocompetent cells. The results indicate that immunological mechanisms are involved in HPV lesions of the oral cavity as they are at other sites. The role of HPV in the etiology of these (and possibly of the oral squamous cell carcinoma) was discussed. Further analyses of the lymphocyte subsets are needed to establish the role of host reactions in the development and eradication of HPV lesions in oral cavity.

The reactivity of Leu 1/T101 monoclonal antibodies (MoAb) was studied in a series of 69 lymphomas with B cell differentiation and was correlated with other cell markers. A three step immunoperoxidase technique on frozen sections was used to test a panel of 20 MoAb: anti-human Ig (heavy and light chains), To 15 (Pan B cells), Leu 1, T101, Leu 4, Leu 3a, Leu 5, OKT 8, OKT 6, Leu 7, anti-CALLA (IOT 5), Leu 10, anti-HLA-DR, OKM 1 and anti-dendritic reticulum cells (R 4/23). T101/Leu 1 antigen was detected in 24 cases: CLL (11 of 11), diffuse centrocytic lymphomas (four of 11), follicular lymphomas (none of 12), follicular and diffuse lymphomas (seven of 10) and one unclassified low grade lymphoma. This antigen was observed in only one high grade malignant lymphoma. In follicular lymphomas, two results deserve attention: (1) T101+ lymphomas showed most frequently IgM+, IgD+ surface Ig. Inversely, T101 unreactive lymphomas displayed IgM+, IgD+ phenotype. (2) Tp67 antigen (T101, Leu 1) and CALLA (GP 100) were found to be mutually exclusive in these lymphomas. These results suggest that follicular lymphomas could be derived from two distinct germinal center cell populations: IgM+ Ig'D-, Calla+, Leu 1-/T101- and IgM+, IgD+, CALLA-, Leu+/T101+.

The combination of viral hepatitis (VH) with thyroid pathology in adolescents leads to an unfavorable course of VH and thyroid disease. The frequency of severe and lingering types of VH with more profound and prolonged shifts of indices of the T- and B-systems of immunity, function of the liver and protein metabolism is increased. Function of the thyroid is sharply suppressed, its euthyroid hyperplasia is often transformed into clinically obvious hypothyroidism.

Immunofluorescence staining for carcinoembryonic antigen, secretory component, and epithelial IgA was evaluated semiquantitatively in routine formalin-fixed mucosal biopsy samples from five patients with ulcerative colitis who had undergone colectomy because of carcinomas. Selected areas were given fluorescence intensity scores without knowledge of whether dysplasia or reactive hyperplasia was present as judged by another observer from conventional histopathological features in adjacent sections. The two types of lesion did not differ significantly with regard to the expression of the three marker antigens. In a prospective study based on cold ethanol-fixed mucosal biopsy samples, lesions from 11 ulcerative colitis patients with dysplasia were compared blindly with lesions from six patients with reactive hyperplasia and with samples obtained endoscopically from eight normal controls. The range of disease-associated fluorescence intensity scores was wide, but staining for all markers tended to be brighter in reactive hyperplasia than in dysplasia (P less than 0.01). In the controls, the fluorescence intensity score tended to be lower for carcinoembryonic antigen but was significantly (P less than 0.01) higher for secretory component and epithelial IgA than in both types of lesion. Moreover, staining for secretory component and epithelial IgA in the lesions seemed to be inversely related to the grade of dysplasia and the degree of inflammation. No such trend was seen for carcinoembryonic antigen. The wide ranges of individual fluorescence scores precluded the possibility of applying carcinoembryonic antigen, secretory component, and epithelial IgA as immunohistochemical markers to differentiate between dysplasia and reactive hyperplasia in routine diagnostic work.

Formalin-fixed tissues from 100 endometria and 50 brains were grouped and studied by the technic of mixed-cell agglutination reaction (MCAR) for studying isoantigens A, B, and H (O). MCAR's were negative in all 45 of the endometria from subjects with endometrial carcinomas, where as MCAR's were positive in the epithelium of endometrial glands of the remaining 55 subjects (cyclic phases of endometrium and benign lesions). MCAR's were negative in all benign and malignant brain tumors and normal brain tissues used in this study. In view of the present findings and in the light of previous observations, the isonatigen loss in adenocarcinomas is greater than such losses in other types of malignancies so far studied. The cause of the negative MCAR's in normal brain tissue and brain tumours is not known, but they may be attributable to lack of isoantigens in normal brain tissue.

The monoclonal antibody (MoAb) DF3 prepared against a membrane-enriched fraction of human breast carcinoma has previously shown a differential reactivity to cytoplasmic antigen in carcinomas versus antigen concentrated on apical borders in benign lesions of the breast. In the present report the cytoplasmic reactivity of MoAb DF3 within a spectrum of benign and malignant breast lesions was studied to define whether the DF3 antigen is expressed in the cytoplasm of potentially premalignant lesions, i.e., atypical hyperplasias, or early malignant lesions, i.e., in situ carcinomas. Biopsy specimens of breast lesions from 108 women, including 28 patients with invasive carcinoma, 12 with in situ carcinoma, 17 with atypical hyperplasia, 25 with proliferative lesions without atypia, and 26 with nonproliferative lesions, were examined for DF3 antigen expression with the use of an indirect immunohistochemical method. Atypical hyperplasias were less reactive with MoAb DF3 than invasive carcinomas (P = .05 by Wilcoxon rank sum test). No significant statistical differences were observed, however, between invasive carcinomas and in situ carcinomas or between in situ carcinomas and atypical hyperplasias on the basis of cytoplasmic DF3 reactivity. Invasive carcinomas, in situ carcinomas, and atypical hyperplasias, however, demonstrated significantly higher reactivity with MoAb DF3 in the cytoplasm than proliferative lesions without atypia and nonproliferative lesions (P less than .01). These studies demonstrate that atypical hyperplasias express elevated levels of a given tumor-associated antigen and thus provide further immunologic evidence that these lesions are premalignant.

The immunocytochemical localization of cells reacting with the OX-8 monoclonal antibody was studied in athymic nude rats by the avidin-biotin-peroxidase complex (ABC) immunoperoxidase technique. By a number of criteria, including morphology and tissue distribution of OX-8-positive cells, it is postulated that the majority of lymphocytes reacting with OX-8 antibody in nude rats are LGL. The cell surface of large lymphocytes reacted with the OX-8 antibody in fixed tissue sections. The tissues with the greatest density and percentages of these reactive cells included the paracortex of lymph nodes in association with interdigitating cell (IDC) hyperplasia, bronchial-associated lymphoid tissue (BALT), the medullary cords and sinuses of lymph nodes, and intestinal epithelium. Ultrastructure of the paracortical areas of IDC hyperplasia revealed granular lymphocytes in close association with IDC. Tissues with the fewest positive cells included bone marrow, B cell areas of lymphoid tissues, and parenchymal epithelial organs. In healthy and cachectic nude rats, various incidental and pathologic lesions contained a significant number of OX-8-positive cells. Large numbers of positive lymphocytes were seen in suppurative pneumonic lesions, enteritis, focal ulcerative epithelial lesions, and papovaviral sialoadenitis. The observation of a large number of OX-8-positive lymphocytes in nonlymphoid organs supports the hypothesis that these cells play a major role in the first line of defense against not only tumors but also infectious agents.

A series of 191 oral mucosal tumors including those with suspected HPV (Human Papilloma Virus) etiology; squamous cell papilloma (SQP), condyloma acuminatum (CA), focal epithelial hyperplasia (FEH), as well as those regarded as unrelated to HPV; fibrous hyperplasia (FH), papillary hyperplasia (PH), and true fibroma (TF), were analyzed for HPV structural proteins (by indirect immunoperoxidase IP-PAP technique), for the presence of epithelial dysplasia, and for the cellular composition (B and T lymphocytes, mononuclear phagocytes, (MPS cells] of their local inflammatory cell infiltrates using ANAE-(acid alpha-naphthyl acetate esterase) stain. HPV structural proteins were disclosed in 85% of FEH, in 75% of CA, and in 41% of SQP. These three lesions significantly differed from PH and FH with regard to the intensity and cellular composition of the local infiltrates, being most intense and B cell predominated in the latter two. Mild dysplasia was found in 20% of both CA and SQP lesions, the former also showing moderate dysplasia in 12% of cases. The HPV antigen positivity was negatively correlated with dysplasia in CA and SQP, the intensity of the infiltrate showing positive association with dysplasia. The results are discussed in terms of HPV etiology of CA, SQP and FEH, of the host immunologic reactivity against these lesions, as well as of the possible role of HPV in human squamous cell carcinogenesis.

For the evaluation of differential diagnostic parameters, hepatocellular carcinoma (HCC, n = 26), liver cell adenoma (n = 4), focal nodular hyperplasia (n = 8), and secondary liver tumors (n = 15) were studied with histologic and immunohistochemical methods. The study was performed on formalin-fixed, paraffin-embedded tissue sections, and, in some cases, also on frozen sections. The diagnostic contribution of the demonstration of alpha-fetoprotein, alpha-antitrypsin, hepatitis B surface antigen, carcinoembryonic antigen (CEA), and biliary glycoprotein I (BGPI), compared with routine hematoxylin-eosin and reticulin stains was evaluated. For the differentiation between HCC, adenoma, and focal nodular hyperplasia, immunohistochemistry contributed less than the strict application of histologic criteria. Immunohistochemistry of CEA and BGPI, however, appeared to be of help in differentiating between primary and secondary liver tumors as follows: CEA is consistently absent in liver cell tumors, while a bile canalicular staining pattern was seen in 80% of HCC due to the presence of BGPI reactivity.

Previous studies from this laboratory have shown that lymphoma and lymph node hyperplasia develop in athymic nude mice injected with Crohn's disease tissue filtrates. In addition, use of an indirect immunofluorescence assay has demonstrated that an antigen(s) in these lymphoid tissues is recognized by sera from patients with Crohn's disease. In our study, one such lymphoma was passed through 10 generations of athymic nude mice and used for immunofluorescence studies. Suspended cells (1 to 5 X 10(8)/mouse) from the primary lymphoma and from the lymphomas that developed in mice of each subsequent generation were injected subcutaneously into groups of three to eight mice. As a control, lymphoma induced in a nude mouse by the injection of sarcoid lymph node filtrate was passed through successive generations in the same manner as the Crohn's disease-induced lymphoma. Lymphoma developed locally in 81% of recipient mice 3 to 6 weeks after injection of suspended cells. In 47 mice, representing 10 generations, Crohn's disease-related lymphoma developed at the sites of injection and at axillary or inguinal lymph nodes. These tumors were examined by immunofluorescence assay using a panel of 20 sera coded for Crohn's disease or control. Immunofluorescence assay yielded positive results in 61% of the lymphomas and 59% of the lymph node with sera from patients with Crohn's disease, but not with control sera. Control lymphomas did not stain with any serum. Our studies demonstrate the transmissibility or inducibility of an antigen(s) in lymphoid tissue of athymic nude mice that is recognized by sera from patients with Crohn's disease, but not by control sera.

Molecular genetic (genotypic) analysis elucidates gene rearrangements within lymphocytes that are responsible for either immunoglobulin production in B-lymphocytes or the expression of cell-surface antigen recognition receptors in T-lymphocytes. Molecular genetic analysis is far more sensitive than immunophenotypic methods for the detection of small clones of lymphocytes because as few as 2 to 5% of cells in an infiltrate can be discovered to possess the same rearranged DNA sequences with genetic probes. In truly polyclonal proliferations, each lymphocyte reorganizes its immunoglobulin or T-antigen receptor genes in a unique manner, resulting in an almost infinite number of combinations of genetic rearrangement and the absence of any new hybridizing bands upon Southern blotting. In monoclonal proliferations, a new, homogeneous, nongermline band is identified on Southern blotting because a sufficiently large number of lymphocytes exhibit an identical genetic rearrangement. In a group of five orbital lymphoid tumors that appeared to be benign reactive hyperplasias by light microscopy and that were polyclonal by immunophenotypic methods, three were found by molecular genetic analysis to harbor small clones of B-lymphocytes with new rearrangement bands on Southern blotting. No clonal abnormalities of T-lymphocytes were found in these five lesions, despite the fact that they were the preponderant cells in the tumors. These observations suggest that "reactive lymphoid hyperplasia" of the orbit may be an unstable lesion, owing to a T-cell immunoregulatory imbalance, with the potential for developing clonal expansions of B-lymphocytes that nonetheless usually remain localized to the orbit.

Sera from patients with Crohn's disease have been reported to show positive immunofluorescence with lymph nodes of nude mice primed with a filtrate of intestinal tissue affected with Crohn's disease. An indirect immunofluorescence assay was used to test sera of 63 unrelated patients with Crohn's disease, 21 with ulcerative colitis and 36 control subjects against lymph nodes of athymic nude (nu/nu) mice which had been injected with Crohn's disease and ulcerative colitis intestinal tissue filtrates. Forty nine per cent of Crohn's disease patients, 10% of ulcerative colitis patients and 3% of control sera reacted against lymph nodes of mice injected injected with ulcerative colitis intestinal tissue filtrates, 18% of Crohn's disease sera were with intestinal tissue homogenate from Dutch Crohn's patients. With the lymph nodes of mice injected with ulcerative colitis intestinal tissue filtrates, 18% of Crohn's disease sera were positive, whereas all ulcerative colitis and control sera were negative. Lymph nodes from 18 of the 19 mice injected with Crohn's disease tissue filtrates reacted with Crohn's disease sera, whereas only three of these 19 mice reacted with ulcerative colitis sera. A comparative study, carried out in parallel with Crohn's disease filtrate induced hyperplastic lymph nodes from the Bilthoven colony (W2) and from the New York colony (E671) using sera from 54 Crohn's disease patients from Leiden, showed immunoreactivity with 44 and 57% of the Crohn's disease sera against the two hyperplastic lymph nodes. Thirty six of the 54 Crohn's disease sera (67%) reacted with either or both lymph nodes. Only 11% of the Crohn's disease sera which were examined for immunofluorescence and lymphocytotoxic antibodies had lymphocytotoxic antibodies, whereas 40% and 46% of the same sera showed positive immunofluorescence against E671 and W2, respectively. Absorption studies indicated that lymphocytotoxic antibodies activity and the immunofluorescence against the primed nude mouse lymph node are mediated by different serum antibodies in Crohn's disease. The reproducibility of the nude mouse immunofluorescence test system for a preferential immunoreactivity of Crohn's disease sera against Crohn's disease tissue primed murine lymph nodes has been confirmed by the present study. Further studies are necessary to find out whether crossreactive antigen(s) as recognised by some of the Crohn's disease sera in mice injected with ulcerative colitis tissue filtrate is similar to the antigen(s) detected by Crohn's disease sera in mice injected with Crohn's disease tissue filtrates.

Carcinoembryonic antigen (CEA) was elevated (greater than 2.5 ng. per milliliter) in 29 of 100 patients with cervical intraepithelial neoplasia (CIN). CEA concentration was related to the amount of intraepithelial neoplasia and to the presence of glandular extension. Lymphoplasmacytic infiltration of tumor cells was unrelated to CEA levels. CEA values returned to normal within 8 weeks following surgery in 77 per cent of patients. A persistently elevated (greater than 5.0 ng. milliter) plasma CEA value following conization was associated with residual CIN in the cervix. These results suggest that sequential CEA determinations may be of value in the follow-up of those cervical cancer patients who initially have high plasma antigen levels.

Cellular hypersensitivity was studied in patients with adenomatous hyperplasia and adenocarcinoma of the endometrium with the use of dinitrochlorobenzene (DNCB) skin tests and inhibition of leukocyte migration by homologous and autologous tumor antigen. Inhibition of leukocyte migration by homologous endometrial carcinoma antigen was found in two of five patients with adenomatous hyperplasia and eight of 11 patients with endometrial adenocarcinoma. A comparable degree of inhibition was found with autologous antigen. DNCB skin reactions were found to be strongly positive in patients with adenomatous hyperplasia, and a lesser degree of reactivity was observed in patients with endometrial adenocarcinoma. No correlation was found between leukocyte migration tests and DNCB reactions, and no correlation was observed between these tests and the age of the patient, clinical stage of disease, or histologic grade of the tumor.

Using monoclonal antibodies (MoAbs) and dual-parameter flow cytometric techniques, bone marrow mononuclear cells (MMC) from patients with resurgent hyperplasia were analyzed for their coexpression of HLe-1 (T200) and antigens normally associated with particular stages of B cell differentiation. The marrow from those with resurgent hyperplasia contained increased numbers of B cell precursors in multiple stages of differentiation compared to controls, thus providing a useful model system for studies of B cell differentiation. These studies indicate that the quantitative expression of T200 is differentiation-related on normal and malignant B cells and B cell precursors. Immature cells express low amounts of T200, while increasing levels of maturity correlated with increasing amounts of the antigen. This study increases the understanding of relationships between B cell surface antigens and T200 and further demonstrates that B cell hyperplasia occurs commonly in association with bone marrow reactive or resurgent processes. The quantitative, rather than only the qualitative, expression of T200 is therefore a useful marker of B cell differentiation in reactive hyperplasia and in further investigation of B cell malignancy.