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PubMed2004

Fluorescence in situ hybridization analysis of chromosome 12p in paraffin-embedded tissue is useful for establishing germ cell origin of metastatic tumors.

The over-representation of chromosome 12p sequences is crucial for the development of invasive testicular germ cell tumors. Testicular cancer patients may have metastatic tumors of diverse histologic types, including adenocarcinoma, undifferentiated carcinoma, sarcoma, or other malignancies that lack features of germ cell tumors. We sought to investigate the possible germ cell origin of such tumors using interphase fluorescence in situ hybridization. In all, 10 metastatic malignant somatic-type tumors from patients with histories of testicular cancer, as well as one malignant somatic-type tumor from a patient with primary mediastinal germ cell tumor were studied and included: adenocarcinoma (five cases), poorly differentiated carcinoma (one), sarcoma (four), and neuroendocrine carcinoma (one). The tumors were analyzed using fluorescence in situ hybridization using 12p spectrum green and 12 centromeric spectrum orange probes in paraffin sections. The patients ranged in age from 27 to 55 years (mean, 43). Colon and lung cancers from patients without germ cell tumors were used as controls. Adequate signals were observed in all tumors. Gain of chromosome 12p was seen in six tumors. None of the control tumors showed 12p amplification. Fluorescence in situ hybridization for 12p amplification in routinely processed surgical specimens is a useful adjuvant diagnostic tool in confirming the germ cell origin of metastatic tumors having the histologic appearance of somatic-type neoplasms.

Adenocarcinoma↗
PubMed1986

Acute lymphoblastic leukemia in infants: evidence for B cell origin of disease by use of monoclonal antibody phenotyping.

Since the prognosis of infants with acute lymphoblastic leukemia (ALL) is so poor, it has been suggested that these leukemias may not be lymphoid in origin, but may originate from stem cell, myeloid, or megakaryocytic progenitors. Alternately it has been hypothesized that these leukemias originate in lymphoid cells at the earliest stages of B cell development. Another possibility is that these leukemias may be of more than one lineage. Therefore we examined leukemic blasts from 12 infants with ALL using monoclonal antibodies to myeloid and lymphoid differentiation antigens. The majority of specimens expressed HLA/DR and reacted with B4 (CD19) but failed to react with stem cell, myeloid, megakaryocytic, or T cell associated antibodies. These results support the speculation that the majority of these leukemias arise in cells at the earliest stages of B cell commitment, and are not of a myeloid or biphenotypic nature.

Antibodies, Monoclonal↗
PubMed1985

B lymphocyte regulation of the immune system. II. Inhibition of Fc receptor expression of lymphocytes by BEF, a lymphokine of B cell origin.

Recently, we described a new lymphokine of B cell origin, capable of selectively preventing the differentiation of T suppressor cells from the precursor into the effector stage. As a result, antibody production against various antigens is markedly increased. We termed this lymphokine B cell-derived enhancing factor (BEF). To discern the mechanism(s) by which BEF interferes with the activation of T suppressor cells, experiments were undertaken to explore the effect of BEF on the induction of Fc receptors (FcR). The induction of FcR on T cells has been implicated in the down-regulation of antibody synthesis, and it has been suggested that the expression of FcR for a given immunoglobulin precedes the release of factors with regulatory functions for the corresponding isotype. In the experiments reported here, murine spleen cells were incubated for 24 hr in the presence of IgG1 or IgA monoclonal antibodies, were washed, and the number of FcR gamma 1+ and FcR alpha+ cells were calculated by a rosette assay. The effect of BEF was studied either during the inductive phase or before, i.e., by pretreating the cells with BEF for 18 hr at 37 degrees C before the inductive phase. Our results show that BEF abolishes, in a dose-dependent manner, the expression of isotype-specific FcR in spleen cells when present during the inductive phase, as well as when cells are pretreated with it. In successive experiments, we tested the effect of BEF on the induction of FcR on T cell-enriched or B cell-enriched spleen cells. The results show that BEF is effective in selectively inhibiting FcR expression on T lymphocytes, but not on B lymphocytes, once isolated from the total spleen cell population. These findings provide further insight into the mechanism by which BEF modulates the immune response, and suggest that different mechanisms may be involved in the induction of FcR on T and B lymphocytes, respectively.

Animals↗
PubMed1998

Advances in periodontal diagnosis. 6. Proteolytic and hydrolytic enzymes of inflammatory cell origin.

Potential proteolytic and hydrolytic enzymes of inflammatory cell origin might serve as biomarkers of periodontal disease activity. The role of these enzymes in periodontal pathology, particularly in respect of collagen and proteoglycan degradation, is discussed. The cellular location of these enzymes and their normal control mechanisms by endogenous inhibitors is described.

Biomarkers↗
PubMed2002

Identification of tumours with the CD43 only phenotype during the investigation of suspected lymphoma: a heterogeneous group not necessarily of T cell origin.

AIMS: CD43 is usually employed as a T cell marker in the immunophenotypic work-up of suspected cases of non-Hodgkin's lymphoma (NHL). In this setting, tumours expressing CD43 in the absence of other T or B cell markers (CD43 only phenotype) are rare. We present four cases with this aberrant phenotype seen at our institution. METHODS: The CD43 only phenotype was defined as expression of CD43 in the absence of expression of B cell markers CD20 and CD79a, and T cell markers CD3 and CD5, on initial immunohistochemistry performed on biopsies of suspected NHL. Combinations of further immunohistochemistry, flow cytometry, cytogenetic analysis and molecular studies were used to enable further diagnosis and lineage assignment. RESULTS: The four cases were subsequently diagnosed as: one case of extramedullary acute myeloid leukaemia, one case of null cell anaplastic large-cell lymphoma, and two cases of extranodal diffuse large B cell lymphoma. None were demonstrated to be of T cell origin. CONCLUSIONS: Our series further confirms the lack of specificity of CD43 expression for T cell lineage. Documentation of the CD43 only phenotype in suspected cases of NHL therefore requires further investigation to both correctly diagnose and clarify lineage of these tumours.

Adult↗
PubMed1987

[Clinicopathological studies on adenocarcinoma of the lung--relationship between subclassification based on cell origin and prognosis of surgical patients].

The relationship between the light- and electron-microscopic subclassification of a tumor based on the morphological similarity to the cell origin and the prognosis of 67 surgical patients with adenocarcinoma of the lung was studied. The prognosis of patients with each subtype was different due to the frequency of metastasis into the lymph nodes. The bronchial gland cell type and the nonciliated bronchiolar cell type consisting of cuboidal cells showed a poorer prognosis than the bronchial surface epithelial cell type (both with and without mucus) and the nonciliated bronchiolar cell type composed of columnar cells. The more unfavorable type as far as prognosis was concerned frequently metastasized into the lymph nodes. In particular, the bronchial gland cell type metastasized into the mediastinal lymph nodes even if the tumors were small in size, and it included more fibrotic focus of the tumors. The cells of the bronchial gland cell type and the nonciliated bronchiolar cell type consisting of cuboidal cells were smaller in cellular size and were connected loosely, but they were arranged in a larger cluster. These findings might explain the reason why these cells frequently metastasized into the lymph nodes. The X-ray films revealed a characteristic appearance corresponding to the subtype. The radiographic findings of the patients with poorer prognosis tended to show three patterns of tumor shadows: more than 5 cm in diameter, dense with spicular radiation, ill-marginated, faint and pseudomorphic with pleural indentation. Subclassification based on cell origin was considered to reflect the degree of malignancy of adenocarcinoma of the lung, and it seemed possible to assess the prognosis of the patients by chest radiographic manifestations.

Adenocarcinoma↗
PubMed1997

Rat GST 8-8 is expressed predominantly in myeloid origin cells infiltrating the gravid uterus.

Previous studies from our laboratory have shown a relatively high expression of rGST8-8 in uterine tissues. This GST isozyme displays relatively high glutathione-peroxidase activity towards lipid-hydroperoxides and towards toxic 4-hydroxyalkenals generated from lipid peroxidation. Since the uterus is a unique organ, subject to oxidative stress due to infiltration by immune effector cells during gestation and because this infiltration is readily identifiable histologically, the studies reported herein were performed to localize the cell specific expression of rGST8-8 to determine whether immune effector cells infiltrating the pregnant rat uterus specifically expressed rGST8-8. A 75 bp end-radiolabeled cRNA probe was prepared from the full length mGSTA4-4 cDNA from the region which is highly homologous with rGST8-8. This cRNA probe was used for in situ hybridization studies to localize rGST8-8 in specific cell types of gravid rat uterus. Results of these studies indicate that this GST isozyme is selectively expressed in myeloid origin cells such as monocytes/macrophages, and neutrophils infiltrating the uterine endometrium and in vascular walls. Selective expression of rGST8-8 in the myeloid origin cells, which are known to generate higher levels of reactive oxygen species, suggests that this GST isozyme plays an important role in the protection mechanisms against lipid peroxidation.

Animals↗
PubMed1987

Malignant lymphomas of follicular center cell origin in man. VI. Large cleaved cell lymphoma.

Between 1970 and 1986 61 patients with large cleaved cell lymphoma (LCCL) were observed and treated. Median age was 56, and there were slightly more women than men (ratio, 1.4:1). Forty-four cases (72%) had both a nodular and diffuse pattern; eight cases were nodular; nine cases were diffuse. Forty-three patients (70%) had Stage III or IV disease; four patients were Stage I (7%); 14 were Stage II (23%). Bone marrow was involved in 15 of 56 evaluable patients (27%). The median survival was 57 months. It was significantly shorter in symptomatic patients (median, 20 months) than in asymptomatic patients (median, 66 months; P = 0.002). Survival time was also shorter in Stage III and IV patients (median, 46 months) compared with Stage I and II patients (median, 100+ months; P = 0.032). Survival was independent of the disease pattern, marrow involvement, age, gender, and surface immunoglobulin heavy or light chain. Among Stage III and IV patients, survival was the same in patients who received therapy initially and in those who were treated expectantly. Among 10 advanced-stage patients who did not initially receive therapy, the median time to beginning therapy was 17 months; five patients received no therapy for 40 to 96 months. Among 14 advanced-stage patients receiving therapy regarded as curative in aggressive lymphoma, 50% experienced a complete remission (CR). However, unlike other aggressive large cell lymphomas, long-term, relapse-free survival was observed in only 9% of patients as the majority of CRs were associated with relapse rather than cure. Despite the fact that it is a large cell lymphoma, LCCL is best regarded as an indolent lymphoma.

Adult↗
PubMed1989

Distinction of influenza viruses of different host cell origin.

Influenza A viruses grown in different animal or human cells retain their antigenic make-up as tested by the usual immunological assays. With the aid of a Sambucus nigra (L.) extract containing its lectins the viruses can be distinguished after one single passage in a different cell type by a change in their hemagglutinating properties. Binding of such lectins to influenza viruses may be a means for a more subtle classification, relating to the host cell origin of the virus.

Animals↗
PubMed2006

Does the signal for the activation of T cells originate from the antigen-presenting cell or the effector T-helper?

The present view is that the antigen-presenting cell (APC) processes and presents simultaneously on its surface several different antigens that are displayed randomly (with respect to their being Self or Nonself) as peptide-MHC complexes. The naive T-cell interacting with its ligand on the APC is activated by "co-stimulation," the first step on the pathway to effectors. This view ignores the requirement for associative recognition of antigen (ARA) in mediating both the Self-Nonself discrimination and the regulation of effector class. The introduction of ARA as a requirement for these two decision functions highlights a critical role for the effector T-helper (eTh) and necessitates rethinking the contribution of the APC.

Animals↗
PubMed2003

Numeric definition of the clinical performance of the nested reverse transcription-PCR for detection of hematogenous epithelial cells and correction for specific mRNA of non-target cell origin as evaluated for prostate cancer cells.

BACKGROUND: Inappropriate quality management of reverse transcription-PCR (RT-PCR) assays for the detection of blood-borne prostate cancer (PCa) cells hampers clinical conclusions. Improvement of the RT-PCR methodology for prostate-specific antigen (PSA) mRNA should focus on an appropriate numeric definition of the performance of the assay and correction for PSA mRNA that is not associated with PCa cells. METHODS AND RESULTS: Repeated (RT-)PCR tests for PSA mRNA in single blood specimens from PCa patients and PCa-free controls, performed by four international institutions, showed a large percentage (approximately equal to 50%) of divergent test results. The best estimates of the mean, lambda (SD), of the expected Poisson frequency distributions of the number of positive tests among five replicate assays of samples from PCa-free individuals were 1.0 (0.2) for 2 x 35 PCR cycles and 0.2 (0.1) for 2 x 25 PCR cycles. Assessment of the numeric value of the mean can be considered as a new indicator of the performance of a RT-PCR assay for PSA mRNA under clinical conditions. Moreover, it determines the required number of positive test repetitions to differentiate between true and false positives for circulating prostate cells. At a predefined diagnostic specificity of > or = 98%, repeated PCRs with lambda of either 1.0 or 0.2 require, respectively, more than three or more than one positive tests to support the conclusion that PSA mRNA-containing cells are present. CONCLUSIONS: Repeated nested PCR tests for PSA and appropriate handling of the data allow numeric quantification of the performance of the assay and differentiation between analytical false and true positives at a predefined accuracy. This new approach may contribute to introduction of PSA RT-PCR assays in clinical practice.

Epithelial Cells↗
PubMed1999

Expression of vascular endothelial growth factor receptor-3 and podoplanin suggests a lymphatic endothelial cell origin of Kaposi's sarcoma tumor cells.

Despite intensive research over the past decade, the exact lineage relationship of Kaposi's sarcoma (KS) tumor cells has not yet been settled. In the present study, we investigated the expression of two markers for lymphatic endothelial cells (EC), ie, vascular endothelial growth factor receptor-3 (VEGFR-3) and podoplanin, in AIDS and classic KS. Both markers were strongly expressed by cells lining irregular vascular spaces in early KS lesions and by tumor cells in advanced KS. Double-staining experiments by confocal laser microscopy established that VEGFR-3-positive and podoplanin-positive cell populations were identical and uniformly expressed CD31. By contrast, these cells were negative for CD45, CD68, and PAL-E, excluding their hemopoietic and blood vessel endothelial cell nature. Podoplanin expression in primary KS tumor lysates was confirmed by Western blot analysis. Both splice variants of VEGFR-3 were found in KS-tumor-derived RNA by RT-PCR. In contrast to KS tumor cells in situ, no expression of VEGFR-3 and podoplanin was detected in any of four KS-derived spindle cell cultures and in one KS-derived autonomously growing cell line (KS Y-1). Our findings that KS tumor cells express two lymphatic EC markers in situ strongly suggest that they are related to or even derived from the lymphatic EC lineage. Lack of these antigens on cultured cells derived from KS lesions indicates that they might not represent tumor cells that grow in tissue culture, but rather other cell types present in KS lesions.

Blotting, Western↗
PubMed1987

Primary cutaneous large cell lymphomas of follicular center cell origin. A clinical follow-up study of nineteen patients.

In this study the clinical characteristics and follow-up data of nineteen patients with a diffuse large cell lymphoma of follicular center cell (B cell) origin, with only skin lesions at presentation, are reported. Sixteen of nineteen patients came to us with localized nodules or tumors, preferentially on the trunk, scalp, and lower legs. Remarkably, eight of eleven patients with disease confined to a limited area on the trunk had a history of slowly progressive papular lesions that had been present for 1 to 20 years prior to the development of rapidly growing skin tumors. Initial treatment, generally radiotherapy and/or polychemotherapy, resulted in complete remissions in seventeen of nineteen patients. Only three patients developed extracutaneous disease, whereas two other patients had recurrent disease in the skin at sites distant from the original skin lesions. Excluding three patients who had just finished initial treatment at the time of writing, twelve of sixteen patients were currently alive and in complete remission with a median survival of 44 months. Four patients died, three of whom were elderly women who had skin tumors on the lower legs when first seen. These results suggest that patients with a primary cutaneous large cell lymphoma of follicular center cell origin with disease confined to the trunk of scalp have a very favorable prognosis.

Adult↗
PubMed1975

Bilateral testicular tumors of germ cell origin.

Four cases of primary testicular tumor of germ cell origin are reported. Three cases were bilateral, while the remaining case involved a unilateral tumor in a non-twin brother of 1 patient with bilateral tumors. Because of the increased likelihood of a second primary tumor developing in a patient who has had a malignant germinal cell tumor and because the changes may be subtle, localized to the testis and occur after a tumor-free interval of many years, careful examination of the contralateral testis and long-term followup are indicated even when systemic chemotherapy for malignancy has been used. This is the seventh time familial occurrence of testis tumors in non-twin brothers has been reported but the first time that one of the brothers had bilateral tumors.

Adolescent↗
PubMed1996

Nasopharyngeal lymphomas: further evidence for a natural killer cell origin.

The authors report four cases of sinonasal lymphomas with immunophenotypic (four cases) and genotypic (three cases) studies. These lymphomas are frequent in Oriental countries, but unusual in Western populations, particularly in France. Although they have been originally considered as T-cell lymphomas, their origin remains unclear, and several authors have recently suggested that they are a natural killer (NK)-cell proliferation. The tumor cells of the four cases reported here showed characteristics of NK cells. On cryostat sections, they were CD3 negative, but CD2 and CD56 positive. The cytoplasm of the tumor cells exhibited azurophilic granulations. Using polymerase chain reaction (PCR), no clonal rearrangement of the T-cell receptor gamma gene was present. Furthermore, clinically, two presented a pharyngeal involvement, and two were also characterized by hepatosplenic involvement at the time of the diagnosis. Thus, the present cases provide additional evidence toward the NK-cell origin of these rare lymphomas. Many sinonasal lymphomas, including the present cases, are positive for Epstein-Barr virus (EBV) (LMP-1 antibody and EBER-messenger RNA probes). This may suggest an important role of EBV as a local factor in their pathogenesis.

Adult↗
PubMed2000

Recurrent or persistent thyroid cancer of follicular cell origin.

Most patients with differentiated thyroid cancer of follicular cell origin have a favorable postoperative course, and their prognosis often appears to be unrelated to the extent of initial surgical treatment in some studies. Important questions that need to be addressed include whether the extent of the initial operation has any impact on the subsequent tumor-free survival and total survival, and whether patients with persistent or recurrent disease benefit from reoperation.

Adenocarcinoma, Follicular↗