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M Ladanyi

Publications and source records attributed to M Ladanyi.

106 records · Page 6Linked to original sources
PubMed1991

Clonal cytogenetic abnormalities in Hodgkin's disease.

Cytogenetic studies of Hodgkin's disease (HD), in contrast to those of non-Hodgkin's lymphoma (NHL), have been limited to small numbers of cases with infrequently recurring aberrations, underscoring the need for additional studies in establishing a coherent cytogenetic picture of HD. Over a 6 1/2-year period, we received 95 specimens of HD for cytogenetic analysis. Analyzable chromosome preparations were obtained in 70 cases, of which 57 (81%) showed only normal metaphases. In the remaining 13 cases (19%), karyotypic abnormalities were observed that were nonclonal in 3 and clonal in 10. The latter 10 cases included 6 of the nodular sclerosis subtype, 3 mixed cellularity, and 1 lymphocyte-depleted; 8 of the specimens were obtained pretreatment and 2 posttreatment. Two of the cases had a clonal numerical aberration, monosomy 17 in one and trisomy 13 in the other, as their sole abnormality. The remaining 8 cases showed complex karyotypes with multiple structural rearrangements; in 3 of these, the abnormal clone was near-tetraploid. Bands involved more than once included 1p36, 1q21, and 4q35, each in 2 cases. Arms involved more than once included 6q (6q13,6q23), 9p (9p13,9p21), and 5q (5q15,5q35). Three patients had loss of part or all of 6q (del(6)(q13),del(6)(q23),i(6p). Bands 14q32 and 18q21 were not involved in any case, contrary to some previous reports. Our results confirm the frequent occurrence of 1p, 1q, and 6q abnormalities in HD. In addition, we have identified a 5q35 breakpoint, which has recently been shown to be highly specific for Ki-1-positive NHL in a case of typical nodular sclerosis HD. Its presence in HD may represent a cytogenetic link between the two entities, which are immunophenotypically related but clinically and histologically distinct.

Aneuploidy↗
PubMed1990

11p13-15 is a specific region of chromosomal rearrangement in gastric and esophageal adenocarcinomas.

In a cytogenetic analysis of 9 gastric and lower esophageal adenocarcinomas, we detected nonrandom rearrangements involving the region 11p13-15 in 8, thus identifying for the first time a specific chromosomal lesion in these tumors. In addition, rearrangements involving 3p21, translocations among the D group chromosomes, and i(5p) were each observed in more than half of the cases. The overall pattern of aberrations encountered in adenocarcinomas of gastric and lower esophageal origin was similar, suggesting that the tumors arising at these anatomical sites are biologically related. We also encountered cytogenetic evidence for gene amplification in the form of homogeneously staining regions and double-minute chromosomes in primary as well as metastatic lesions, which is consistent with amplification of a number of cellular oncogenes in these tumors detected by others and us at the molecular level. These cytogenetic findings are discussed in relation to nonrandom chromosome abnormalities and gene amplification reported in other types of adenocarcinoma.

Adenocarcinoma↗
PubMed1990

Gene amplification in gastric and esophageal adenocarcinomas.

In a United States series of 28 gastric/esophageal adenocarcinomas of poorly to moderately differentiated histopathology, we detected gene amplification in 21% of the tumors. Using the modified DNA in-gel renaturation assay to detect down to 7-8 copies of amplified DNA sequences, we identified 3 gastric tumors with amplified DNA sequences and confirmed by Southern hybridization analysis that HER-2/neu was amplified greater than 5-fold in these specimens. Immunohistochemical staining of tumor tissue sections with p185 HER-2/neu antibodies demonstrated that only the 3 gastric adenocarcinomas with corresponding HER-2/neu gene amplification displayed membrane immunoreactivity. Amplification of c-met was identified in 2 tumors, and this was the first study to assay for multiple copies of this protooncogene in fresh gastric tumor tissues. Amplification of c-erbB was observed in one tumor, and no evidence for amplification of int-2 was obtained in this series of adenocarcinomas.

Adenocarcinoma↗
PubMed1990

Cytogenetic and immunohistochemical evidence for the germ cell origin of a subset of acute leukemias associated with mediastinal germ cell tumors.

Most acute leukemias occurring in patients with mediastinal germ cell tumors (MGCTs) appear to be primary rather than therapy-related; however, no data have been obtained to date to confirm the hypothesized germ cell origin of the leukemias in this syndrome. We identified six male patients with this syndrome treated at Memorial Sloan-Kettering Cancer Center: in all six, the leukemia was studied immunohistochemically for various hematologic and germ cell antigens; in four, the karyotype of the leukemia was available; in one, the MGCT had also been karyotyped. In three patients, we found evidence of a germ cell origin of the acute leukemias. A 19-year-old male developed an acute myeloblastic leukemia 11 months after presenting with an MGCT; karyotypes of the two tumors showed them to be clonally related, both showing an i(12p), a cytogenetic marker of germ cell tumors. A 16-year-old male with probable Klinefelter's syndrome presented simultaneously with acute monocytic leukemia and an MGCT; although the MGCT was not karyotyped, the leukemia showed an i(12p). A 23-year-old male developed concurrently an MGCT and acute myelomonocytic leukemia; the leukemia cells coexpressed myelomonocytic antigens (HAM56, My4, My9) and cytokeratin, suggesting dual differentiation, myeloid and germ cell. Evidence for a germ cell origin of the acute leukemias in the three other patients was not obtained, although in all three the MGCT and the leukemia occurred simultaneously, supporting an etiologic relationship. Hence, these leukemias may represent another form of non-germ cell malignancy developing in germ cell tumors. All patients died of the leukemia, with a median survival of less than 2 months. This syndrome may be a useful pathologic model for the study of germ cell differentiation and hematopoietic ontogeny.

Adolescent↗
PubMed1990

Cytogenetic and molecular analysis of human male germ cell tumors: chromosome 12 abnormalities and gene amplification.

We report karyotypic analysis of 24 male germ cell tumors (GCTs) with clonally abnormal karyotypes biopsied from testicular and extragonadal lesions from 20 patients belonging to the histologic categories seminoma, teratoma, embryonal carcinoma, choriocarcinoma, and endodermal sinus tumor. Chromosomes 1, 7, 9, 12, 17, 21, 22, and the X chromosome were nonrandomly gained in these tumors. Nonrandom structural changes affected most frequently chromosomes 1 and 12, the latter as i(12p) and/or del(12)(q13----q22). The i(12p) was seen in 90% of tumors which included all histologic subtypes and gonadal as well as extragonadal presentation. Our present results, along with those from published data on fresh GCT biopsies, establish that i(12p) is a highly nonrandom chromosome marker of all histologic as well as anatomic presentations of GCTs. in contrast, we found del(12)(q13----q22) exclusively in nonseminomatous GCTs (NSGCTs) and mixed GCTs (MGCTs) occurring in 44% of such lesions. Because successful cytogenetic analysis of fresh tumor specimens is not always possible, we developed a method based on DNA analysis to detect i(12p) as increased copy number of 12p. In addition to the changes affecting chromosome 12 identified above, we have detected, for the first time, cytological evidence of gene amplification in the form of homogeneously staining regions (HSRs) and double minute chromosomes (dmins) in treated as well as untreated primary extragonadal and metastatic GCTs and confirmed the presence of amplified DNA in one of these tumors at the molecular level by the in-gel renaturation method. Hybridization of DNA from cultured cells from an HSR-bearing tumor with a panel of probes for genes known to be amplified or otherwise perturbed in diverse tumor systems did not identify the amplified gene, suggesting amplification of a novel gene or genes. This study comprises the largest series of GCT cytogenetics attempted so far. Notably, it includes data on a series of primary mediastinal tumors, a group which previously has not been studied in any detail.

Blotting, Southern↗
PubMed1990

Immunohistochemical, molecular, and cytogenetic analysis of a consecutive series of 20 peripheral T-cell lymphomas and lymphomas of uncertain lineage, including 12 Ki-1 positive lymphomas.

Although several independent series of non-Hodgkin's lymphomas (NHLs) have been subjected to cytogenetic studies or analyses of lineages by assaying for clonal immunophenotypes and clonal rearrangements affecting immunoglobulin (IG) and T-cell receptor (TCR) genes, no published reports exist of series of non-B-cell NHLs on which cytogenetic, immunohistochemical, and IG and TCR gene rearrangement studies have been undertaken together. Among 343 NHLs ascertained prospectively between January 1984 and December 1988 at the Memorial Sloan-Kettering Cancer Center, 278 cases with clonal chromosome abnormalities were identified. Of the latter, 20 were non-B-cell NHLs, which in turn comprised 15 peripheral T-cell lymphomas (PTCLs) and 5 lymphomas of uncertain lineage (LULs). The LULs either were biogenotypic, had discordant immunophenotype and immunogenotype, or showed no evidence of B-cell, T-cell, or histiocytic derivation. Of the 15 PTCLs, eight expressed the Ki-1 antigen and four of these had translocations involving the band 5q35 [t(5q35)]. Of the five LULs, four expressed the Ki-1 antigen and one of these had a translocation involving band 5q35. Previous studies have associated t(5q35) with Ki-1 positive NHLs characterized histologically by a pleomorphic diffuse large cell morphology. In our series of 12 Ki-positive non-B-cell NHLs, five (42%) had a 5q35 translocation. They were histologically indistinguishable from the subset without the translocation. The frequent lineage uncertainty exhibited by Ki-1 positive NHLs of similar histology and cytogenetic abnormalities suggests their derivation from an early uncommitted lymphoid cells.

Antigens, Differentiation↗
PubMed1990

Ki-1 antigen expression defines a favorable clinical subset of non-B cell non-Hodgkin's lymphoma.

Immunohistochemical and immunophenotypic analyses were performed on 278 cases of karyotypically abnormal non-Hodgkin's lymphoma (NHL). Excluding cases of lymphoblastic lymphoma or mycosis fungoides, 20 cases showed evidence of non-B cell lineage. T cell lineage was proven by genotypic and immunophenotypic analyses in 15 of the 20 cases; five were of ambiguous lineage. All of the non-B lineage cases were of diffuse histology with a large cell component (DLCL). Twelve cases expressed the Ki-1 antigen; five of these cases also demonstrated a translocation with a break at 5q35. Patients with Ki-1 positive DLCL and t(5q35) had a younger median age compared with non-B cell DLCL without t(5q35). The Ki-1 positive patients had a higher frequency of skin involvement and lower incidence of bone marrow involvement compared with Ki-1 negative DLCL. Survival analysis was performed on 86 cases of B cell DLCL and 18 cases of non-B cell DLCL which were serially ascertained prior to receiving cytotoxic chemotherapy. Median duration of complete remission was significantly longer in the B cell compared with the non-B cell DLCL groups; there was only a trend for decreased overall survival in the non-B cell group. Among the subset of non-B cell lymphomas, overall survival of patients with Ki-1 expressing DLCL was significantly longer than those with Ki-1 negative DLCL, who had a median survival of less than a year. These results show that immunophenotypic, immunohistochemical, and cytogenetic markers can define subsets of patients with non-B cell lymphomas with differing clinical characteristics and outcome.

Adolescent↗
PubMed1989

Benign metastasizing giant cell tumors of bone. A DNA flow cytometric study.

Approximately 2% of histologically benign giant cell tumors (BGCT) of bone are complicated by lung metastases, which can progress despite their benign histologic appearance. Almost all BGCT studied by DNA flow cytometry (FCM) have been reported to be diploid. However, the very few cases with lung metastases previously analyzed were all aneuploid. To assess the usefulness of DNA FCM in predicting the metastatic potential of BGCT, seven metastasizing BGCT were studied by DNA FCM using paraffin-embedded tissue. Five were purely diploid, one was tetraploid, and one was aneuploid. The primary and the metastasis showed the same DNA distribution in all but the tetraploid case, in which the metastasis was purely diploid. A single patient, who was in the diploid group, had unresectable tumor in the lungs; she remains alive with stable disease at 30 months. The other six patients, who underwent complete resections of their lung metastases, are free of disease. These results suggest that DNA FCM is not a sensitive method for predicting the metastatic potential of BGCT since most metastasizing cases appear to be diploid.

Aneuploidy↗
PubMed1989

Leukemic differentiation of a mediastinal germ cell tumor.

The biological basis for acute leukemia associated with mediastinal germ cell tumors has remained unexplained due to lack of critical data that would illuminate the genetic relationship between the two tumors in a given patient. Here we present results of serial cytogenetic investigations on the pretreatment and posttreatment mediastinal yolk sac tumor and immature teratoma biopsies and two separate leukemic bone marrow aspirates from a patient who developed acute nonlymphocytic leukemia 11 months after the initial diagnosis of the germ cell tumor. Presence of an i(12p) in all tumor clones and trisomy 21 in one clone in the posttreatment mediastinal tumor and all leukemic clones establishes the common origin of all tumor clones and shows that in this case the leukemia was derived from the malignant germ cell clone.

Adult↗
PubMed1988

Mediastinal germ cell tumors and histiocytosis.

Two cases of mediastinal germ cell tumors associated with primary hemoproliferative disorders are reported. The first case was a 23-year-old man who presented simultaneously with a mediastinal immature teratoma with focal yolk sac differentiation and a cytologically benign histiocytic proliferation associated with refractory thrombocytopenia. In the second case, an unsuspected mediastinal immature teratoma with focal yolk sac and hepatic differentiation was found postmortem in a 33-year-old man who had died of fulminant malignant histiocytosis. Although the histiocytosis in the former case failed to fulfill all the usual diagnostic criteria of malignant histiocytosis, both cases probably represent different manifestations of the same pathologic process. Review of the 19 published cases of hematologic malignancies associated with mediastinal germ cell tumors and of related experimental studies suggests a role for yolk sac differentiation in the pathogenesis of this syndrome.

Adult↗
PubMed1987

Estrogen and progesterone receptor determination in the papillary cystic neoplasm of the pancreas. With immunohistochemical and ultrastructural observations.

Two cases of papillary cystic neoplasm (PCN) of the pancreas occurring in 18- and 34-year-old women are described. In both, the clinicopathologic features were typical. Immunohistochemical staining for neuron-specific enolase (NSE), S100 protein (S100), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and several peptide hormones was negative. Alpha-1-antitrypsin immunoreactivity was prominent, and its significance is discussed. Ultrastructural features were most compatible with partial acinar differentiation. Of the well-described cases of PCN, approximately 95% have occurred in women between the ages of 12 and 35, suggesting a role for hormonal factors in the pathogenesis of this tumor. Consequently, tumor tissue from one patient was assayed for estrogen and progesterone receptors: significant levels of high-affinity receptors were demonstrated for both hormones. Assays for the same receptors in five normal pancreases were negative. This constitutes the first reported measurement of these receptors in the PCN; the results indicate that the PCN may be another hormone-sensitive tumor.

Adolescent↗
PubMed1987

Pulmonary involvement in giant cell arteritis.

While clinically suspected in some cases, pulmonary lesions in giant cell arteritis have rarely been described pathologically. We report the findings at autopsy in an elderly woman with typical giant cell arteritis. In addition to inflammation of temporal and other major systemic vessels, large- and medium-sized pulmonary arteries showed focal necrosis as well as medial granulomatous inflammation. These findings, as well as a review of previous clinical and pathologic reports, emphasize that the disease can affect the lungs and may rarely be a significant cause of morbidity.

Aged↗
PubMed1986

In-vivo labeling of (3H)D-aspartate uptake sites in monkey retina.

Following prolonged topical application of (3H)D-aspartate in vivo, selective labeling of three distinct cell classes was observed in light-microscopic radioautographs from squirrel monkey retina. Müller (glial) cell bodies and their processes were intensely and consistently labeled in all preparations. Moderately labeled perikarya were occasionally detected in the area of bipolar cells, within the inner nuclear layer. These were particularly numerous in sections from the central retina where an intense diffuse labeling of the inner plexiform layer was also prominent. Finally, moderate to dense accumulations of label were observed over the cell bodies, internal segments and fiber processes of cone photoreceptors. These results strongly suggest that cones, as well as a sub-population of bipolar cells, use glutamate and/or aspartate as neurotransmitter(s) in monkey retina.

Administration, Topical↗
PubMed1985

CNV and time estimation.

We investigated the hypothesis that the development and resolution of CNV waves may, in part at least, reflect time estimation processes in the nervous system. Specifically, we postulated that subjects with a high degree of accuracy in time estimation tasks will show a fast resolution of the negativity following the imperative stimulus (S2). The results showed that, consistent with the hypothesis, accurate estimators, as a group, show CNVs with faster resolution of negativity after S2. In addition, they have CNVs of lower amplitude and show a slower rise time to peak negativity than subjects with poor time estimation abilities.

Adult↗