Search PubMed⌕ Search

Biomedical subjects

S Heim

Publications and source records attributed to S Heim.

At least 109 records · Page 6Linked to original sources
PubMed1995

Clonal heterogeneity in breast cancer: karyotypic comparisons of multiple intra- and extra-tumorous samples from 3 patients.

Intratumor phenotypic heterogeneity is one of the characteristics of breast carcinomas, and genetic mechanisms are likely to contribute to it. We have studied breast cancer clonal heterogeneity by cytogenetic analysis of multiple tumor samples (one from each tumor quadrant) as well as samples of macroscopically normal surrounding breast tissue from 3 patients with this disease. Clonal chromosome aberrations were found in all 8 successfully analyzed samples from the carcinomas. Two to 6 cytogenetically unrelated clones were detected in each case, unevenly distributed among the tumor quadrants. Karyotypic abnormalities were also found in 4 out of 9 macroscopically tumor-free samples from the surrounding tissue; in 2 of these samples, a ductal carcinoma in situ was detected histologically, and the cytogenetic evidence suggests that the remaining 2 samples also contained neoplastic cells. Quantitative analysis of the findings revealed a statistically significant higher frequency of karyotypically abnormal cells in samples with a histologic diagnosis of carcinoma vs. samples without any detected malignancy. That cells bearing cytogenetic evidence that they belong to the tumor parenchyma are left behind during breast-conserving surgery for carcinoma of the breast may account for the relatively high long-term local relapse rates seen in this disease.

Adult↗
PubMed1995

Chromosomal abnormalities involving 11q13 are associated with poor prognosis in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: In individual patients with squamous cell carcinoma of the head and neck (SCCHN), established prognostic factors do not satisfactorily predict clinical outcome. Although the karyotype is an independent prognostic factor in certain hematologic malignancies and solid tumors, no data have been reported concerning the possible relationship between chromosomal abnormalities and clinical outcome in patients with SCCHN: METHODS: In 116 cases of primary SCCHN, short term cultures were analyzed cytogenetically during 1987 through 1991, the karyotypes were divided into four groups: k1, normal (n = 35); k2, numeric changes only (n = 31); k3, simple structural abnormalities (n = 27); and k4, complex karyotypes (n = 23). The patients were followed for at least 18 months after diagnosis or until death. RESULTS: The 2-year survival rate was lower in the k4 subgroup (35%) than in the k1, k2, and k3 subgroups taken together (61%), both in the series as a whole (P = 0.02), and in the largest tumor site subgroup, laryngeal squamous cell carcinoma (n = 32), (P = 0.04). The most prevalent breakpoint was in chromosome band 11q13, occurring in 11 tumors, 10 of which belonged to the k4-subgroup. The 2-year survival rate was lower for patients with 11q13 rearrangements (20%) than for those without (60%), both in the series as a whole (P = 0.001), and in the k4-subgroup (P = 0.02). CONCLUSIONS: The results suggest that in SCCHN the presence of a complex karyotype is associated with poor prognosis, particularly when 11q13 rearrangements are present.

Adult↗
PubMed1995

Chromosome abnormalities in bilateral breast carcinomas. Cytogenetic evaluation of the clonal origin of multiple primary tumors.

BACKGROUND: Although acquired somatic mutations presumably are crucial in carcinogenesis, nothing is known about the chromosome aberrations of bilateral breast carcinomas. METHODS: Eighteen specimens from 16 bilateral carcinomas were analyzed cytogenetically. The banding analysis was supplemented with fluorescence in situ hybridization with painting probes. RESULTS: In two cases, the finding of the same clonal abnormalities in samples from both breasts indicated that the bilaterality had arisen through a metastatic process. In the remaining cases, the absence of similarities between the two sides indicated an independent origin of the two carcinomas. Also, in multifocal lesions within the same breast, examples were found both of karyotypically related and unrelated clones. Altogether, multiple clones without similarities were detected in nine specimens, sometimes together with other, karyotypically related clones. There was no indication that bilateral carcinomas of the breast are cytogenetically different from unilateral ones. The following chromosomal abnormalities were recurrent: der(1;16)(q10;p10), del(1)(q11-n12), del(1)(q42), and del(3)(p12-n13p14-n21). CONCLUSIONS: Bilateral breast carcinomas have the same cytogenetic aberrations, including evidence of polyclonality, as unilateral carcinomas. The majority apparently arise independently, but some result from a metastasis from one breast to the other. In this sense, bilateral breast carcinomas are similar to multifocal breast cancer in general, of which bilateral tumors may represent a special case.

Aged↗
PubMed1995

Cytogenetically detected clonal heterogeneity in a duodenal adenocarcinoma.

A primary duodenal adenocarcinoma, a tumor type for which no previous chromosome data existed, was cytogenetically analyzed after short-term culture. The main tumor mass was localized in the pancreatic head, but the histopathologic examination revealed its duodenal origin. A total of six abnormal, karyotypically unrelated, clones were identified. The largest exhibited clonal evolution and consisted of two subclones with massively rearranged karyotypes in the hypodiploid and hypotetraploid range. Chromosome imbalances brought about by these complex changes were gain of 1q, losses of chromosomes 6 and 9, and total or partial losses of 1p, 3p, 3q, 9p, 10p, 17p, 17q, 18q, 20p, and 20q. The remaining five smaller clones had 1-2 numerical or balanced structural chromosome aberrations. The present study thus revealed yet another epithelial tumor type characterized by karyotypically unrelated clones. For this as for other tumors, the pathogenetic significance of such cytogenetic polyclonality remains uncertain.

Adenocarcinoma↗
PubMed1995

The incidence of complications in endoscopic anterior thoracolumbar spinal reconstructive surgery. A prospective multicenter study comprising the first 100 consecutive cases.

STUDY DESIGN: A prospective multicenter study on 100 consecutive surgical procedures. OBJECTIVES: A prospective multicenter study was performed to evaluate the early perioperative complications in 100 endoscopic spinal procedures--78 video-assisted thoracic surgical procedures and 22 laparoscopic lumbar instrumentation and fusion procedures. SUMMARY OF BACKGROUND DATA: Endoscopic procedures have been widely applied in general surgery for appendectomy, cholecystectomy, liver resection, Nissen fundoplication, colon resection, and hernia repairs. Video-assisted thoracic surgery is widely used for pleural biopsy, lung resection, and sympathectomy. This is the first large series to date investigating the safety and potential complications using endoscopic surgery for anterior decompression or fusion of the thoracolumbar spine. METHODS: Video-assisted thoracic surgical procedures included multilevel anterior thoracic releases for deformity, 27 patients; anterior thoracic discectomies with spinal canal decompression, 41 patients; pyogenic vertebral osteomyelitis decompression, 2 patients; and vertebral corpectomy for neurologic decompression, 8 patients. Mean operative time was 2 hours, 34 minutes (range, 45 minutes to 6 hours), and mean length of stay was 4.97 days (range, 2-21 days). Anterior laparoscopic interbody stabilization and fusion at L4-5 or L5-S1 was performed in 22 patients. The mean operative time was 4 hours, 17 minutes (range, 2 hours, 40 minutes to 9 hours), and the mean length of stay was 5.6 days (range, 1-23 days). RESULTS: The most common video-assisted thoracic surgical complications were transient intercostal neuralgia (six patients) and atelectasis (five patients). The most common laparoscopic complication was bone graft donor site infection (two patients). There were two endoscopic cases that were converted to open procedures, one for extensive pleural adhesions and one for a common iliac vein laceration. CONCLUSIONS: The endoscopic spinal approaches proved to be safe operative procedures in 100 consecutive cases. There were no permanent iatrogenic neurologic injuries and no deep spinal infections.

Blood Loss, Surgical↗
PubMed1995

Nonrandom chromosome abnormalities in short-term cultured primary squamous cell carcinomas of the head and neck.

We report the finding of clonal chromosome abnormalities in short-term cultures from 44 squamous cell carcinomas of the head and neck region. Eleven tumors had gain or loss of the Y chromosome, sometimes one clone with +Y and another with -Y, as the sole anomaly, whereas the remaining 33 all carried structural rearrangements and usually were cytogenetically complex with multiple aberrations. The chromosomal bands most frequently involved were, in decreasing order of frequency, 8p11-q11, 1p11-q11, 3p11-q11, 11q13, 13p11-q11, 1p13, 5p11-q11, 7p11-q11, 15p11-q11, and 14p11-q11. Almost one-half of the breakpoints were located in centromeric or juxtacentromeric bands. Recurrent aberrations included i(8q), i(5p), i(1q), del(3)(p11-12), del(5)(p11), t(1;1)(p13;q25), and der(14;15)(q10;q10). To see whether the karyotypic features of head and neck squamous cell carcinoma differ depending on exact tumor site, we added to the present series our previously published 23 karyotypically abnormal head and neck squamous cell carcinomas that had been cultured in the same way as the tumors of the present series. In the ensuing correlation analysis, tumors of the oral cavity and oropharynx and hypopharynx were found to share many features: highly complex karyotypes were frequent, often containing isochromosomes such as i(8q) and i(5p), and also rearrangements of 11q13 (often as homogeneously staining regions) and loss of genetic material from the short arms of chromosomes 3, 13, 14, and 15 were repeatedly seen. Laryngeal carcinomas, on the other hand, often had simple karyotypic changes.

Adult↗
PubMed1995

Cytogenetic findings in malignant peripheral nerve sheath tumors.

Clonal chromosome aberrations were detected in 8 short-term cultured malignant peripheral nerve sheath tumors (MPNST). Seven had a near-triploid chromosome number and I was in the hyperhaploid-hypodiploid range. No recurrent structural rearrangements were found; the bands most frequently involved (3 tumors) were 7p11, 12p13 and 14q11. The most common numerical changes were loss of a sex chromosome (all tumors) and loss of at least 1 copy of chromosomes 8, 16 and 22 (4 tumors). Pooling our data with those on the 20 previously published MPNST with abnormal karyotypes, we found that the chromosome number has often been in the triploid range (12 tumors), with stem line variation between 34 and 270. All chromosome arms, except 22p and the Y chromosome, were involved in recombinations. The most frequently rearranged bands were 7p22 (6 tumors) and 1p21, 7p11 and 14q11 (5 tumors each). Most numerical and unbalanced structural aberrations have led to loss of genetic material, in particular from Xq26-qter (13 tumors); 11q22-qter and 13p (12 tumors); 9p22-pter, 11p13-pter, 17p and 17q11-21 (11 tumors); 1p22-32 and 1p34-pter (10 tumors) and 6q25-qter and chromosome 16 (9 tumors).

Adolescent↗
PubMed1995

Karyotypic features of malignant tumors of the nasal cavity and paranasal sinuses.

Cytogenetic analysis of short-term cultures from 6 tumors of the nasal cavity and paranasal sinuses--one esthesioneuroblastoma, 2 adenocarcinomas and 3 squamous-cell carcinomas (SCC)--revealed clonal chromosome aberrations in all cases. The esthesioneuroblastoma had a complex hyperdiploid karyotype. None of the aberrations was similar to those previously described in short-term cultures or established cell lines from esthesioneuroblastomas. The 2 adenocarcinomas had complex karyotypic changes, which in both cases included rearrangements of bands 9p22 and 14q11. One SCC had 5 unrelated pseudodiploid clones, 1 displayed a highly complex karyotype, including rearrangement of band 11q13, and 1 had simple karyotypic changes with loss of 6q material and gain of 3q. These findings are similar to those described in head-and-neck SCC at other sites.

Adenocarcinoma↗
PubMed1995

Chromosome abnormalities in benign hyperproliferative disorders of epithelial and stromal breast tissue.

Cytogenetic analysis of short-term cultures from 15 cases of benign proliferative breast disease (PBD), 10 diffuse PBD and 5 papillomas, and 15 fibroadenomas of the breast revealed clonal chromosome abnormalities in 7 diffuse PBD lesions, 4 papillomas and 5 fibroadenomas. The remaining 14 cases had a normal female chromosome complement. Cytogenetically unrelated abnormal clones were seen in 4 fibroadenomas and 2 PBDs. A single abnormal clone was found in 9 PBDs and 1 fibroadenoma. Three clonal abnormalities were seen as recurrent changes in 6 cases, namely interstitial deletions of 3p with 3p 12-14 as the minimally common deleted segment (in 1 papilloma, 1 diffuse PBD with atypia and 1 mixed-pattern lesion with both papilloma and atypical diffuse PBD features), r(9)(p24q34) (in 1 diffuse PBD and 1 fibroadenoma), and del(1)(q12)(again in 1 diffuse PBD and 1 fibroadenoma). Intriguingly, 6 of the 16 abnormal cases had chromosome changes that have been seen repeatedly as primary abnormalities in breast carcinomas: der(16)t(1;16)(q10;p10), del(3)(p12p14), and del(1)(q12). We conclude that some of the chromosome anomalies frequently found in breast carcinomas are also present in PBD and fibroadenomas. These aberrations may be accepted as early, neoplasia-relevant mutations. However, they do not seem to be sufficient by themselves to unleash a malignant process.

Breast↗
PubMed1995

Karyotypic characterization of colorectal adenocarcinomas.

Cytogenetic analysis of short-term cultures from 52 primary colorectal adenocarcinomas revealed clonal chromosome aberrations in 45 tumors, whereas the remaining 7 had a normal karyotype. More than 1 abnormal clone was detected in 26 tumors; in 18 of them, the clones were cytogenetically unrelated. The modal chromosome number was near-diploid in 32 tumors and near-triploid to near-tetraploid in 13. Only numerical aberrations were identified in 13 carcinomas, only structural aberrations in 3, and 29 had both numerical and structural changes. The most common numerical abnormalities were, in order of decreasing frequency, gains of chromosomes 7, 13, 20, and Y and losses of chromosomes 18, Y, 14, and 15. The structural changes most often affected chromosomes 1, 17, 8, 7, and 13. The most frequently rearranged chromosome bands were, in order of decreasing frequency, 13q10, 17p10, 1p22, 8q10, 17p11, 7q11, 1p33, 7p22, 7q32, 12q24, 16p13, and 19p13. Frequently recurring aberrations affecting these bands were del(1)(p22), i(8)(q10), i(13)(q10), and add(17)(p11-13). The most common partial gains were from chromosome arms 8q, 13q, and 17q and the most common partial losses from chromosome arms 1p, 8p, 13p, and 17p. A correlation analysis between the karyotype and the clinicopathologic features in our total material, which consists of altogether 153 colorectal carcinomas, including 116 with an abnormal karyotype, showed a statistically significant association (P < 0.05) between the karyotype and tumor grade and site. Carcinomas with structural chromosome rearrangements were often poorly differentiated; well and moderately differentiated tumors often had only numerical aberrations or normal karyotypes. Abnormal karyotypes were more common in rectal carcinomas than in carcinomas situated higher up. Near-triploid to near-tetraploid karyotypes were more than twice as frequent in tumors of the distal colon as in those of the proximal colon and rectum. The cytogenetic data indicate that carcinomas located in the proximal colon and rectum, which often are near-diploid with simple numerical changes and cytogenetically unrelated clones, probably arise through different mechanisms than do tumors located in the distal colon, which more often have complex near-triploid to near-tetraploid karyotypes.

Adenocarcinoma↗
PubMed1995

Fluorescence in situ hybridization analysis of whole-arm 7;12 translocations in hematologic malignancies.

Cytogenetic analysis of one case of acute myeloid leukemia (AML), one of acute lymphoblastic leukemia (ALL), one of refractory anemia with excess of blasts (RAEB), and one of acute mixed lineage leukemia (AMLL) with unbalanced 7;12 translocations mapped the breakpoints to the centromeres on both chromosomes. The rearrangements were interpreted as the whole-arm translocations der(7;12)(q10;q10) in the AML and ALL and der(7;12)(p10;q10) in the RAEB and AMLL. However, further analysis by metaphase and/or interphase fluorescence in situ hybridization (FISH) showed centric fusion only in the AML and ALL. In the RAEB and AMLL, centromeric material from chromosome 7 but not from 12 was present in the derivative chromosome. Whereas the t(7;12) resulted in loss of 12p in all four cases, the corresponding chromosome 7 imbalances differed--monosomy for 7q in the RAEB and AMLL and monosomy for 7p in the AML and ALL. Six hematologic neoplasms with unbalanced whole-arm or near-centromeric 7;12 translocations and seven dic(7;12) with juxtacentromeric breakpoints have been reported previously: 2 AML, 1 RAEB in transformation, and 10 ALL. All karyotypically informative cases had loss of 12p material. All but one of the cases with combined 7p and 12p deletion were ALL, whereas all cases with 7q and 12p loss showed myeloid differentiation. No particular clinical, morphologic, or immunophenotypic features seem to characterize ALLs with t(7;12). AMLs with an unbalanced t(7;12), often together with 5q deletions, might be associated with previous genotoxic exposure and poor prognosis.

Adult↗
PubMed1995

Deletion of 1p loci and microsatellite instability in colorectal polyps.

Previous cytogenetic studies have indicated that a subset of large bowel adenomas have distal 1p deletions. We addressed this question by examining 70 sporadic polyps (63 adenomas, 5 hyperplastic polyps, and 2 polyps of undetermined histology) from 55 patients for alterations at eight loci on the short arm of chromosome 1 and found allelic imbalance (AI) or loss of one allele (LOH) in 14 (20%). The locus most frequently changed was MSI, which maps to 1p33-35. Fluorescence in situ hybridisation with centromeric and telomeric probes for chromosome 1, performed for 11 polyps, did not yield an abnormal number of signals, in accordance with the interpretation that the observed AI and LOH were the result of interstitial deletions in 1p. Whereas allelic imbalance at five other loci (mapping to 5q, 8p, 10p, 11p and 17q) was found less frequently, and then mainly in large (> 2 cm) tumours, the 1p alterations were equally distributed among small (< 1 cm) and large polyps. They were preferentially found in left-side tumours. Instability at microsatellite loci--the mutator phenotype--is demonstrated by shifts in the electrophoretic mobility of normal alleles. The mutator phenotype was first associated with hereditary nonpolyposis colorectal cancer but is also occasionally found in sporadic colorectal carcinomas; however, it is still uncertain when in the adenoma-carcinoma sequence in this type of genomic instability arises. We therefore looked for it at 12 dinucleotide repeat loci and found that seven tumours (six adenomas and one hyperplastic polyp) from seven patients had acquired new alleles not seen in the patients' corresponding normal DNA. Our results suggest that inactivation of a putative suppressor gene distally in chromosome arm 1p is an early event in colorectal tumourigenesis. They also show that microsatellite instability can be detected in large bowel polyps, indicating that this phenomenon, too, probably plays a pathogenic role for some colorectal tumours early in the adenoma-carcinoma sequence.

Adenoma↗
PubMed1995

Massive cytogenetic heterogeneity in a pancreatic carcinoma: fifty-four karyotypically unrelated clones.

Chromosome analysis after short-term culture revealed remarkable cytogenetic heterogeneity in a pancreatic carcinoma. The patient had no prior history of radio- or chemotherapy. A total of 54 aberrant, near-diploid, karyotypically unrelated clones were identified, three of which displayed clonal evolution. The abnormalities were unbalanced in 30% of the clones. From one to eight karyotypic anomalies per clone were found. Numerical changes were rare, whereas structural aberrations were numerous and diverse and included deletions, duplication, insertions, inversions, translocations, ring formation, and telomeric associations. All chromosomes except No. 15 were involved in structural rearrangements, chromosomes 1, 6, 7, 8, 11, and 12 being the most frequently affected. A similarly massive cytogenetic polyclonality has never been reported previously. Although the spectrum of epithelial neoplasms characterized by karyotypically unrelated clones is increasing, the pathogenetic role of this type of cytogenetic intratumor heterogeneity remains unknown.

Aged↗
PubMed1995

Tetraploidization and progressive loss of 6q in a squamous cell carcinoma of the parotid gland.

Cytogenetic analysis of short-term cultures from a squamous cell carcinoma (SCC) of the parotid gland revealed one clone with loss of the Y chromosome only, as well as three related subclones: 91,XXYY,add(6)(q21), -11,t(11;22)(q13;q11),ins(15;?)(q22;?)[cp5+ ++]/91,XXYY,add (6)(q21), -11,add(11)(p11), ins(15;?)(q22;?),der(22)t(11;22)(p11;q11)[2]/91,XXYY,add(6)(q11), -11,add(11)(p11),ins(15;?)(q22;?),der(22) t(11;22)(p11;q11) [cp4]. The finding of only one copy of all structurally rearranged chromosomes in a near-tetraploid karyotype indicates that tetraploidization was an early event in tumorigenesis. Rearrangements, in particular deletions, of 6q have previously been associated with adenoid salivary gland malignancies. Our finding of progressive 6q loss with clonal evolution, combined with the fact that 6q deletions were also seen in the two previously reported SCCs of the salivary glands, indicate that loss of genetic information from this chromosome arm is characteristic for most types of salivary gland carcinomas, irrespective of their histologic differentiation.

Aged↗