Biomedical subjects

S Heim

Publications and source records attributed to S Heim.

At least 145 records · Page 8Linked to original sources

PubMed1994

Cytogenetic heterogeneity in a clear cell hidradenoma of the skin.

Short-term cultures from a clear cell hidradenoma, a benign skin tumor for which no chromosome data exist, were cytogenetically analyzed. A total of eight unrelated aberrant clones were identified. The karyotypic profiles of two separately processed parts of the sample--a tumor nodule and seemingly normal adjacent dermal tissue--were different. Characteristic for the tumor nodule was a single abnormal clonal population consisting of three subclones: 46,XY,der(2)inv(2)(p13q23)t(2;9)(p13;q22), der(9)t(2;9)(q23;q22),t(11;19)(q21;p13),t(12;19)(q24;p13)/46,idem, inv(1)(p32q44)/92,idemx2. The adjacent tissue contained, in addition to the clone found in the tumor nodule, a spectrum of unrelated clones, the largest of which also showed clonal evolution: 45-47,XY,t(3;6)(p25;p25),t(12;17)(q15;q12),-17,+r(17)x2 [cp]/45-47,idem,inv(5)(p15q22)/90-94,idemx2. The remaining six clones found in this part were small and had simpler numerical or structural aberrations. The multiclonal pattern observed in this hidradenoma seems to reflect both cytogenetic convergence and divergence during neoplastic progression. The presence of unrelated clones may be an indication that the tumor was of multicellular origin.

Acrospiroma↗

PubMed1994

Acute myeloid leukemia (AML-M1) with multiple trisomies and t(8;21)(q22;q22).

Cytogenetic analysis of an acute myeloid leukemia (AML-M1) showed the karyotype 53,XY, +6, +8,t(8;21)(q22;q22), +9, +10, +13, +19, +21. Only one AML with a massively hyperdiploid karyotype (> 50 chromosomes) and t(8;21) has been published before. A comparison of the two cases reveals similarities both with regard to the morphologic subtype (M1) and to which chromosomes were trisomic (+6, +8, +13, +19, and +21 were found in both cases). We surmise that the t(8;21) was the primary chromosomal abnormality and that the set of multiple trisomies occurred secondarily; this pattern of clonal evolution may have favored a more immature leukemic phenotype in these two cases than is regularly seen in t(8;21)-associated leukemias.

Child↗

PubMed1994

Interrelationship between methodological choices and conceptual models in solid tumor cytogenetics.

Scientific methods and models are interdependent. That the techniques one uses determine which findings one gets, is evident. But equally important is the influence of our a priori expectations; they may cause us to choose inadvertently those methods that are most likely to yield results that appear to confirm an already preconceived picture of reality. The conceptual models and methods of solid tumor cytogenetics are to a large extent inherited from leukemia and lymphoma cytogenetics. We illustrate how this may bias the generation and interpretation of new findings, especially when carcinomas are investigated. These malignant epithelial tumors much more often harbor cytogenetically unrelated clones than do hematologic or mesenchymal neoplasms. Carcinoma cytogenetics is therefore extremely susceptible to selection differences, making the results heavily dependent on which sample is processed, how it is disaggregated, how and for how long the cells are cultured, and on how the analysis is performed and the results presented. This calls for more efforts to be directed toward establishing also the phenotypic nature of those cells that are being karyotyped. As one cannot yet quality-grade most clonal chromosome changes in any reliable manner, meaning that one cannot determine to what extent each aberration or each clone contributes to the neoplastic process, statements about the "true" karyotypes of tumor parenchymas should be viewed with suspicion. A complete carcinoma karyotype may be much more complex than extrapolations from the analysis of a few cells may lead one to believe.

Chromosomes, Human↗

PubMed1994

Characteristic karyotypic features in lacrimal and salivary gland carcinomas.

Short-term cultures from 12 non-squamous cell carcinomas (NSCCs) of the head and neck were cytogenetically investigated. Three tumours were acinic cell carcinomas, two adenoid cystic carcinomas, three mucoepidermoid carcinomas, two carcinomas in pleomorphic adenoma, and two adenocarcinomas. Clonal chromosome aberrations were detected in all but one adenocarcinoma. Including our data, a total of 40 head and neck NSCCs with clonal aberrations have been described. Deletions of the long arm of chromosome 6 are the most common aberrations (11/40 cases); they have been detected in all types of NSCC except carcinoma in pleomorphic adenoma. Two aberrations seem to be closely associated with tumour type: t(6;9)(q21-24;p13-23), which has been seen in three of 11 adenoid cystic carcinomas (in two as the sole aberration), and structural rearrangements of 8q12-13, which have been detected in three of four carcinomas in pleomorphic adenoma.

Adenocarcinoma↗

PubMed1994

Cytogenetic analysis of multifocal breast carcinomas: detection of karyotypically unrelated clones as well as clonal similarities between tumour foci.

Cytogenetic analysis was performed on short-term cell cultures of two foci (A and B) from each of three multifocal breast carcinomas. In case I, four clones (three related and one unrelated) were detected in sample A. In sample B, two of the three related clones and the unrelated clone seen in A were found, as was also a third subclone showing a pattern of clonal evolution slightly different from that detected in A. In cases II and III, multiple cytogenetically unrelated clones were found in A and B, with only one clone being shared by both foci in each case. Our finding of cytogenetic similarities between macroscopically distinct tumour lesions indicates that the multifocality reflects intramammary tumour spread rather than the synchronous emergence of pathogenetically independent carcinomas within the same breast. On the other hand, the detection of karyotypic heterogeneity in the form of cytogenetically unrelated clones in all foci suggests that human breast carcinoma may be polyclonal. This polyclonality may be part of the explanation for the cellular heterogeneity commonly seen at the phenotypic level in breast cancer.

Aged↗

PubMed1993

Cytogenetic findings in 33 osteosarcomas.

Thirty-three osteosarcomas (OS) were analyzed cytogenetically. Clonal chromosome changes were detected in 17 cases. Six tumors had chromosome numbers in the diploid range, 6 in the triploid range, 1 in the tetraploid range and 1 in the pentaploid range, while 3 tumors had multiple clones with different ploidy levels. Including the present 17 tumors, a total of 27 OS with clonal aberrations have been reported. The recognizable structural rearrangements in these 27 tumors clustered to chromosome arms 1p, 1q, 3p, 3q, 7q, 11p, 17p and 22q. Chromosome bands 1q11, 1q21, 1q42 and 7q11 were the most frequently rearranged, and the most common numerical rearrangements were -3, -10, -13 and -15. Supernumerary ring chromosomes, in 2 tumors as the sole change, were found in all 3 parosteal OS, which is in agreement with the findings in 1 previously reported parosteal OS. The association between ring formation and parosteal morphology represents the first cytogenetic-morphologic entity among OS.

Adolescent↗

PubMed1993

Aberrations of chromosome segment 12q13-15 characterize a subgroup of hemangiopericytomas.

BACKGROUND: In later years, several characteristic acquired chromosomal aberrations have been identified in mesenchymal tumors. Many of these aberrations, either alone or with histopathologic and clinical data, are useful in diagnosis. The cytogenetic profile of hemangiopericytomas has been poorly investigated. METHODS: Short-term cultures from four spindle cell tumors were cytogenetically analyzed. RESULTS: Clonal acquired chromosome aberrations were found in three of the four tumors: inv(12) (q14q24) in a malignant hemangiopericytoma, a supernumerary der(3)t(3;12) (p21-23;q13-15) in a benign hemangiopericytoma, and t(6;12;19) (p21;q13;p13) in a spindle cell sarcoma that was histologically a malignant hemangiopericytoma or a synovial sarcoma. The fourth tumor, a malignant hemangiopericytoma, had a normal karyotype. The tumors with inv(12) and t(6;12;19) had subclones with trisomy 5 in addition to the structural changes. CONCLUSIONS: The current findings and the literature data indicate that a subgroup of hemangiopericytomas is characterized by rearrangement of chromosome segment 12q13-15.

Adult↗

PubMed1993

Chromosome abnormalities in eighty-three head and neck squamous cell carcinomas: influence of culture conditions on karyotypic pattern.

Short-term cultures from 115 squamous cell carcinomas (SCC) of the head and neck were cytogenetically investigated. Thirty-six of the tumors have been reported previously, whereas 79 are new cases. The material was divided into two series based on the medium used. The 80 tumors of series I were cultured in RPMI 1640 supplemented with fetal calf serum, glutamine, antibiotics, insulin, cholera toxin, and epidermal growth factor. The 35 tumors of series II were cultured in a chemically defined, serum-free medium with a low calcium concentration, MCDB 153, which stimulates epithelial growth while inhibiting fibroblasts. A total of 83 tumors with clonal karyotypic abnormalities were detected in the two series. Series II had a higher proportion of tumors with complex karyotypic changes than series I (43% versus 15%), a lower proportion of tumors with pseudo- or neardiploid clones characterized by simple rearrangements (3% versus 34%), and a lower frequency of unrelated clones (3% versus 24%), indicating that the different culture conditions favored growth of different cell populations. Except for rearrangements of 1p22, which were mainly found in series I, the distribution of breakpoints in structural aberrations was similar in the two series and clustered to several chromosomal bands or regions, in particular 11q13, 1p22, 1p11-12, 3p11-q11, 5q13, 1q25, 15q10, and 8q10. Unbalanced structural aberrations were more common in series II, frequently leading to loss of segments from chromosome arms 3p, 7q, 8p, 11q, 13p, 14p, and 15p, whereas gain of genetic material often involved chromosome arms 1q, 3q, 8q, and 15q.

Aged↗

PubMed1993

Deletion of 1p36 as a primary chromosomal aberration in intestinal tumorigenesis.

Cytogenetic analysis of short-term cultures from benign intestinal tumors revealed clonal chromosome aberrations in five colorectal adenomas, one adenoma of the papilla Vateri, and one hyperplastic polyp of the rectum. One adenoma had numerical aberrations only, but in all other tumors structural rearrangements were found that led to loss of genetic material from 1p. In three of the cases, the deletion was restricted to the 1p36 band; the rest had lost larger 1p segments. The rearrangement of chromosome 1 was the sole karyotypic anomaly in three adenomas, all with mild or moderate dysplasia, and in the hyperplastic polyp. Both adenomas that had additional aberrations beyond the 1p loss showed severe dysplasia. We conclude that cytogenetically detectable loss of genetic information from 1p36 is an early, seemingly primary, premalignant event in intestinal tumorigenesis. The fact that the adenomas with 1p- as the sole change showed only mild or moderate dysplasia and that the del(1p) was found also in the hyperplastic polyp suggests that this aberration is more related to the induction of hyperproliferation than to differentiation disturbances in the intestinal mucosa.

Adenoma↗

PubMed1993

Comparative cytogenetic and DNA flow cytometric analysis of 150 bone and soft-tissue tumors.

Samples from 48 benign and 102 malignant bone and soft-tissue tumors were analyzed cytogenetically and by DNA flow cytometry. Clonal chromosome abnormalities were found in 82 tumors and normal karyotypes in 68; 61 tumors were DNA-non-diploid and 89 were diploid. The cytogenetically abnormal tumors were used for comparison between the 2 types of investigation; 45 of these tumors were DNA-diploid and 37 were DNA-non-diploid. There was, with few exceptions, good correspondence between the quantitative estimates of genomic changes by the 2 methods, indicating that the cells cytogenetically analyzed from short-term cultures are representative of the in vivo cell populations. Discrepancies were primarily found in cases with indexes above 1.5, in which the DNA index was higher than the chromosome index. The chromosome analysis suggested that skewed stemline (G0/G1) peaks in the diploid region in DNA histograms indicate the presence of cell populations with small net quantitative genomic changes, although not all such populations were detected by DNA flow cytometric analysis. The view that one of the peaks in bimodal stemline DNA histograms with narrow peaks represents a non-diploid cell population was also corroborated. On average, the cell populations giving rise to double stemlines in DNA histograms showed quantitatively larger genomic changes than those that gave rise to broad or skewed diploid G0/G1 peaks. The findings indicate that these histogram profiles are not artifactual but reflect chromosomal changes in the tumor parenchyma.

Bone Neoplasms↗

PubMed1993

Cytogenetic aberrations in colorectal adenocarcinomas and their correlation with clinicopathologic features.

BACKGROUND: Little is known about the karyotypes of colorectal carcinomas and, in particular, about how the cytogenetic findings correlate with clinicopathologic features. METHODS: Short-term cultures from 49 colorectal adenocarcinomas were analyzed cytogenetically. The karyotypes were correlated with grade, stage, lymphocytic infiltration, and site (using the chi-square test), with patient age and tumor size (using the Student t test), and with survival (using the log-rank or Mantel-Haenszel test). RESULTS: Normal karyotypes were detected in 17, simple numeric changes in 22, and multiple structural and numeric abnormalities in 10. The most common numeric aberrations were +7, -Y, -18, and -22. The most common structural rearrangements were, in decreasing order of frequency, of chromosomes 1 (eight samples, leading to loss of 1p material in five), 3, 11, 17, 6, 8, 13, and 20. Marked or moderate lymphocytic infiltration was seen significantly less often (P < 0.05) in tumors with complex chromosomal abnormalities than in those with simple anomalies or normal karyotypes. The subset of patients who had tumors with multiple chromosomal abnormalities had a significantly shorter survival time (P < 0.025) than those who had lesions with simple changes or normal karyotypes. CONCLUSIONS: Loss of 1p material is the most consistent chromosomal change in colorectal carcinomas but probably represents a progressional rather than a primary event. Structural changes of chromosomes 3 and 11 seem to be more common in tumors located in the distal part of the large intestine. The significantly shorter survival time of patients with complex aberrations indicates that the karyotype could be used as a prognostic parameter in patients with colorectal cancer.

Adenocarcinoma↗

PubMed1993

[The value of nerve biopsy in the diagnosis of familial amyloidosis].

Nerve biopsies are useful for the etiological diagnosis of certain polyneuropathies. One of them is familial amyloidotic polyneuropathy, which can be diagnosed and specified on the basis of a Kongo-red stain and immunohistochemical analysis of the amyloid deposited in the nerve. This possibility is illustrated by a case report. A review of the various clinical, morphological and genetic aspects of these diseases is given.

Adult↗

PubMed1993

Chromosome analysis of 20 breast carcinomas: cytogenetic multiclonality and karyotypic-pathologic correlations.

Short-term cultures from 20 breast carcinomas were analyzed cytogenetically. A normal female chromosome complement was found in 4 cases. Clonal chromosome aberrations were detected in 16 tumors. In 10 tumors, multiple cytogenetic clones were found; in 2 cancers the clones were related, reflecting clonal evolution, but in the remaining 8 tumors the clones were cytogenetically unrelated, indicating clonal heterogeneity in the origin of the tumor parenchyma. Correlation analysis between karyotypic and pathologic parameters indicated that cases with complex karyotypes and/or cytogenetically unrelated clones, when compared with cases with a single simple karyotypic abnormality, were generally of higher histologic malignancy grade, had more mitoses in the histologic sections, and also more often had carcinoma in situ lesions in the same breast.

Aneuploidy↗

PubMed1993

Rearrangement of band q13 on both chromosomes 12 in a periosteal chondroma.

Cytogenetic analysis of a recurrent periosteal chondroma revealed nonreciprocal translocations of both chromosomal segments 12q13-->qter, from one chromosome 12 to 7q32 and from the homologous chromosome 12 to 16q22. The remaining parts of the two chromosomes 12 formed a dicentric chromosome. This is the second reported chondroma with a 12q13-15 rearrangement, and changes of this chromosome region consequently seem to be nonrandom occurrences in chondromas.

Adult↗

PubMed1993

Interstitial deletion of the short arm of chromosome 3 as a primary chromosome abnormality in carcinomas of the breast.

Interstitial deletions of the short arm of chromosome 3 were found in short-term cultures of five breast carcinomas (of 41 breast cancers with clonal aberrations analyzed by us during the same period). They were the only clonal structural change in three tumors; in the remaining two, the clone with 3p-coexisted with seemingly unrelated clones that had other structural and numerical aberrations. The deletions were identical, del(3)(p12p14), in four cases. The fifth tumor seemed to have a smaller deletion, interpreted as del(3)(p13p14). Our findings constitute karyotypic evidence that 3p deletions are relatively common in breast carcinomas and concur with the molecular genetic detection of loss of heterozygosity in this chromosome arm. The fact that the deletions were found as solitary changes indicates that loss of genetic information from 3p loci is an early, possibly primary, event in tumorigenesis.

Adenocarcinoma, Mucinous↗

PubMed1993

Trisomy 7 in nonneoplastic cells.

The somatic mutation theory of tumorigenesis states that mutations are necessary for tumor development. On the other hand, acquired, clonal chromosomal alterations are occasionally detected in otherwise normal, nonneoplastic cells--for example, loss of sex chromosomes occurs in bone marrow cells and lymphocytes in elderly individuals--and it is therefore evident that not all mutations are by themselves sufficient for neoplasia to occur. Thus, the finding of an acquired, clonal chromosomal abnormality does not constitute proof that a lesion is neoplastic. Trisomy 7 has, as the sole clonal chromosomal aberrations, been reported in a wide variety of epithelial tumor types but also in some mesenchymal and neurogenic neoplasms. It has been suggested to be a primary, i.e., tumor-initiating, abnormality in tumors of the bladder, brain, colon, kidney, lung, ovary, prostate, and thyroid. But data from cytogenetic studies of solid tumors, macroscopically normal tissue in the proximity of solid tumors, and nonneoplastic lesions now question the importance of a solitary +7 as a neoplasia-associated change. Most solid tumors in which trisomy 7 has been found as the sole change in one clone have also displayed other, cytogenetically unrelated, clones with complex karyotypic abnormalities. Such karyotypic differences among coexisting clones could indicate that the neoplasm is polyclonal, that the cytogenetically disparate clones have emerged during tumor progression from one original clone carrying submicroscopic genomic changes only, or that the clone with +7 does not represent the tumor parenchyma. The latter interpretation is supported by the finding of cells with trisomy 7 in macroscopically normal tissue outside tumors of the brain, kidney, and lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Transformation, Neoplastic↗

PubMed1993

Chromosome aberrations in tenosynovial giant cell tumors and nontumorous synovial tissue.

Five tenosynovial giant cell tumors--4 pigmented villonodular synovitis (PVNS) and 1 nodular tenosynovitis (NTS)--were investigated cytogenetically. Clonal chromosome aberrations were detected in 3 of them. One PVNS had t(7;16)(q22;q24) as the sole anomaly, whereas 1 PVNS and the NTS displayed aberrations suggesting clonal evolution: t(1;19)(p11;p12)/t(1;19), +12 and ins(5;1)(q31p34)/ins(5;1),t(2;4)(p23;q21), respectively. Including our 3 cases, a total of 6 tenosynovial giant cell tumors with karyotypic changes have been reported. Apart from 2 PVNS with trisomies 5 and 7, and 2 NTS with rearrangement of chromosome band 1p13, no recurrent chromosome change has been detected. Although the detection of clonal, acquired chromosome abnormalities has formerly generally been accepted as sufficient to conclude that a lesion is neoplastic, the interpretation of the pathogenetic significance of the karyotypic aberrations in synovial tumors is obscured by the fact that we have also detected comparable aberrations in obviously nonneoplastic synovial tissue. One of 2 lesions from patients with hemorrhagic synovitis carried a clonal del(13)(q12q21), and 2 of 4 synovectomy samples from patients with rheumatoid arthritis displayed -Y and -Y together with +7. The available cytogenetic data therefore cannot be used to resolve the controversy as to whether tenosynovial giant cell tumors are truly neoplastic or only reactive, inflammatory proliferations.

Adult↗

PubMed1993

Chromosome painting as a supplement to cytogenetic banding analysis in non-Hodgkin's lymphoma.

Chromosomal in situ suppression (CISS) hybridization with biotin labeled chromosome-specific libraries was performed on short-term cultures from five cases of non-Hodgkin's lymphoma (NHL). The painting analysis proceeded in three stages. First-stage CISS hybridization was done with libraries specific for chromosomes that seemed to be lost or rearranged as judged by banding analysis. Second-stage CISS included hybridization with probes specific for chromosomes that, because of banding pattern similarities, were considered to be likely candidates to have contributed unidentified chromatin blocks in the abnormal karyotype. The third and final stage was a confirmation hybridization with a library specific for the chromosome that, at the stage two analysis, was found to have donated the previously unknown chromosomal segment. The aberrant chromosomes were often more complex than the banding analysis had led us to believe. Among the rearrangements whose nature was determined by CISS hybridization were two add(1)(p36) which, in both cases, were shown to be a der(1)t(1;2)(p36;q31). This study illustrates the potential use of chromosome painting in resolving karyotypic uncertainties in NHL, and it shows that new cytogenetic subgroups may emerge when classical banding analysis is supplemented with fluorescence in situ hybridization techniques.

Biotin↗