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ABSTRACT: Non-small cell lung cancer (NSCLC) is one of the most aggressive tumors, with a very low overall survival rate. We investigated surgically resected squamous cell carcinoma (SCC) and adenocarcinoma (AC) to identify chromosomal imbalances and their value for individual prognostication.
A total of 80 cases, including 55 SCC and 25 AC, were retrospectively analyzed by comparative genomic hybridization. To model the sequential cytogenetic events, an oncogenetic tree model was applied based on maximum likelihood estimation. Clinicopathologic data and follow-up data were correlated with chromosomal imbalances.
Fifty-one percent of patients were in stage I, 32% in stage II, and 17% in stage III, without statistically significant differences in staging distribution between SCC and AC. The average number of copy number imbalances was higher in SCC than in AC (9.4±1.2 vs 5.4±1.1; p=0.11). Frequency of chromosomal imbalances at -3p, +3q, -4q, +5q, -5q, +7q, and -13q were significantly different between SCC and AC. Subsequently, oncogenetic tree modeling identified different clusters of chromosomal imbalances for SCC and AC. Appearance of the -3p-cluster in SCC was associated with decreased overall survival independent of clinicopathologic parameters (mean, 42.8±7.5 months vs 80.1±9.1 months, log rank p=0.019), whereas in AC no prognostic value could be identified for specific clusters of chromosomal imbalances.
Although, the limited number of analyzed cases allows a cautious statement on chromosomal imbalances, the oncogenetic tree modeling suggests distinct patterns of cytogenetic evolution for SCC and AC with implications for clinical outcome in SCC.
The Annals of thoracic surgery 09/2011; 92(3):1038-43. · 3.74 Impact Factor
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Angelika Gutenberg,
Almuth Brandis,
Bujung Hong, Bastian Gunawan,
Christina Enders,
Inga-Marie Schaefer,
Ralf Burger,
Helmut Ostertag,
Michael Gaab,
Joachim K Krauss,
Laszlo Füzesi
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ABSTRACT: Primary papillary tumors of the central nervous system and particularly the pineal region are rare. Papillary tumor of the pineal region (PTPR) is a recently described neoplasm that has been formally recognized in the 2007 World Health Organization Classification of Tumors of the Nervous System. Because of their rarity, further pheno- and genotypical observations as well as therapeutic experience are necessary to differentiate PTPR from other primary or secondary papillary tumors of this region. We herein present three cases of PTPR characterized by local recurrence in two of them. Primary and recurrent tumors were analyzed by immunohistochemistry and comparative genomic hybridization (CGH). From our results clonal chromosomal aberrations can be postulated which seem to be a feasible tool to differentiate PTPRs from other primary or secondary papillary tumors of this region.
Brain Pathology 04/2011; 21(6):672-7. · 3.99 Impact Factor
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Inga-Marie Schaefer,
Christina Enders,
Andreas Polten,
Florian Haller,
Andreas M J Frölich,
Silke Cameron,
Philipp Schüler,
Peter Schweiger, Bastian Gunawan,
Alexander Beham,
László Füzesi
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ABSTRACT: Basaloid squamous cell carcinoma (BSCC) and carcinosarcoma of the esophagus are rare entities, making up fewer than 2% of esophageal malignancies. Comparative genomic hybridization (CGH) in 1 case of BSCC and 2 cases of carcinosarcoma and subsequent array CGH in 1 case each of BSCC and carcinosarcoma revealed common chromosomal gains at 2p25.3-2p12, 7q21.3-7q22.3, and 11q13.2-11q13.4. Chromosomal losses at 13q31qter were observed in both carcinosarcomas. In addition, progression of genomic instability from in situ to invasive carcinosarcoma could be demonstrated by using array CGH. Our observations suggest a common genetic origin of BSCC and carcinosarcoma.
American Journal of Clinical Pathology 04/2011; 135(4):579-86. · 2.60 Impact Factor
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Bernhard C Danner,
Jan S Gerdes,
Klaus Jung,
Björn Sander,
Christina Enders,
Torsten Liersch,
Ralf Seipelt,
Angelika Gutenberg, Bastian Gunawan,
Friedrich A Schöndube,
Laszlo Füzesi
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ABSTRACT: Pulmonary metastases (PM) are frequent in colorectal carcinoma (CRC). However, little is known about the chromosomal imbalances in CRC that accompany metastatic pulmonary disease. We investigated tumor specimens of CRC (n=30) and their corresponding PM by comparative genomic hybridization (CGH). There were no substantial differences in the degree of chromosomal instability between CRC and PM, neither in average number of copy alterations (ANCA; 6.6 ± 0.8 and 7.7 ± 0.9) nor in gains (2.6 ± 0.5 and 2.6 ± 0.4), losses (3.6 ± 0.5 and 4.8 ± 0.6), or amplifications (0.4 ± 0.1 and 0.3 ± 0.1). Basically, similar patterns of chromosomal imbalances could be identified in both CRC and corresponding PM, most frequently including chromosomal gains at 7, 8q, 13q, and 20q, as well as losses at 4, 8p, 18q, and 20p. CRC and corresponding PM differed in frequencies for losses at chromosome arm 5q (3 vs. 26%; P=0.012). Losses at 4q and 11q in CRC were significantly associated with lower 5-year survival rates (80 vs. 24%, P=0.026 and 74 vs. 17%, P=0.007, respectively), and they may represent candidates for adverse prognostic markers in primary CRC.
Cancer Genetics 03/2011; 204(3):122-8.
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ABSTRACT: In gastrointestinal stromal tumors (GISTs), the occurrence of an epithelioid/mixed phenotype has been correlated to PDGFRA mutations, gastric localization and favorable outcome. On the other hand, the prognostic significance of an epithelioid/mixed growth pattern occasionally observed in GISTs with KIT mutation is unclear. The aim of this study was to evaluate the prognostic significance of an epithelioid/mixed phenotype in correlation to anatomical localization, genotype, and expression of cell-cycle markers in a series of 116 primary GISTs with KIT mutation on a tissue microarray. Independent of their anatomical localization, the majority of KIT-mutated GISTs displayed a pure spindled phenotype (72%), with the remaining tumors showing an epithelioid/mixed growth pattern. In KIT-mutated GISTs from the stomach, the occurrence of an epithelioid/mixed growth pattern was significantly correlated with larger tumor diameters (P=0.005), higher mitotic counts (P=0.0001), high-risk category (P=0.001), higher expression of the G2-phase cell-cycle marker cyclin B1 (P=0.04), higher expression of the G1 to M-phase proliferation marker Ki67 (P=0.02) and a significantly shorter disease-free survival (P=0.003) compared with tumors with pure spindled morphology. In contrast, there were no significant differences between pure spindled and epithelioid/mixed GISTs from the small/large bowel. Our findings indicate that the epithelioid/mixed phenotype in KIT-mutant gastric GISTs represents a secondary tumor growth pattern associated with tumor progression and adverse outcome, probably through accelerated G1/S-phase restriction point passage.
Modern Pathology 02/2011; 24(2):248-55. · 4.79 Impact Factor
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Cancer genetics and cytogenetics 12/2010; 203(2):341-4. · 1.54 Impact Factor
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ABSTRACT: Information on structural chromosomal changes in brain metastases (BM) of colorectal carcinoma (CRC) is very limited. Therapeutic and diagnostic strategies to reduce the risk of BM have potential impact on cancer mortality. By using comparative genomic hybridization, the primary CRC of 11 patients and their corresponding 13 BM were analyzed. BM showed significantly more mean chromosomal aberrations than the primary CRC (13.6+/-2.1 vs. 7.9+/-1.9, P=0.03), significantly more chromosomal gains (7.2+/-0.9 vs. 3.5+/-0.9, P=0.01), and tended to have also more losses (6.1+/-1.4 vs. 4.0+/-1.1, P=0.29). Changes that occurred significantly more often in BM than in primary CRC were gains of 8q, 12p, 12q, and 20p, as well as losses of 5q. BM of CRC show a significantly higher chromosomal instability in comparison to primary tumors. The prevalently altered genomic regions in the metastases of this study are likely to harbor genes that play an important role in the genesis of brain-specific metastasis.
Cancer genetics and cytogenetics 04/2010; 198(1):47-51. · 1.54 Impact Factor
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Cancer genetics and cytogenetics 02/2010; 197(1):95-8. · 1.54 Impact Factor
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ABSTRACT: To determine the prognostic impact of p16INK4A expression in gastrointestinal stromal tumours (GISTs), which is currently being questioned, with both loss and overexpression said to be correlated with poor prognosis.
Two different forms of p16INK4A were identified, presenting with predominantly nuclear and cytoplasmic expression pattern, respectively. The immunohistochemical expression of the two forms and their correlation with E2F1 and prognosis were analysed in a series of 120 GISTs with clinical follow-up. Low nuclear p16INK4A expression correlated with E2F1 up-regulation, higher mitotic counts, and tumour progression. The prognostic value of nuclear p16INK4A expression was only marginally significant (P=0.05). Strong expression of the cytoplasmic p16INK4A form was significantly associated with shorter disease-free survival (P=2x10(-5)). The prognostic impact of strong expression of the cytoplasmic p16INK4A form was independent of anatomical localization, tumour size and mitotic counts, and significant even among the cohort of tumours with high malignant potential.
Low expression of the nuclear p16INK4A form and strong expression of the cytoplasmic p16INK4A form both represent two independent parameters each associated with tumour progression in GISTs. Low nuclear p16INK4A expression enables E2F1 up-regulation and consecutive accelerated cell proliferation. In contrast, strong cytoplasmic p16INK4A expression probably reflects a negative feedback loop as a result of (as yet unknown) oncogenic events.
Histopathology 02/2010; 56(3):305-18. · 3.08 Impact Factor
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ABSTRACT: The molecular biology and clinical behaviour of gastrointestinal stromal tumours (GISTs) are associated with their anatomical localization (stomach or intestine), and also with the mutation status of the receptor tyrosine kinases KIT and PDGFRA. Twelve GISTs were evaluated for differential miRNA expression signatures by use of microarrays representing 734 human miRNAs. Thirty-two miRNAs were found to be differentially expressed according to localization and mutation status. Differential expression was further analysed and confirmed for four miRNAs (miR-132, miR-221, miR-222, and miR-504) by qRT-PCR in 49 additional GISTs. Differentially expressed miRNAs were functionally mapped to KIT/PDGFRA signalling and G1/S-phase transition of the cell cycle, revealing 22 predicted miRNA/mRNA interactions for ten gene targets from KIT/PDGFRA signalling, and 12 interactions for 12 gene targets of G1/S-phase transition. Moreover, the expression of 44 miRNAs clustered in a genetically imprinted region at 14q32.31 was found to be strongly correlated in the microarray analysis. This was confirmed for two selected miRNAs (miR-134 and miR-370) from the 14q32.31 cluster by qRT-PCR in 49 additional GISTs, and the expression of these two miRNAs was significantly lower in GISTs with 14q loss, and also in GISTs with tumour progress. miRNA profiling may prove to be a key determinant of the biology and clinical features of GISTs.
The Journal of Pathology 08/2009; 220(1):71-86. · 6.32 Impact Factor
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ABSTRACT: Gastrointestinal stromal tumors (GIST) are mesenchymal tumors of the gastrointestinal tract supposed to arise from the cells of Cajal because of gain-of-function mutations of the tyrosine receptor kinases c-kit or platelet-derived growth factor receptor A. Imatinib selectively inhibits the kinase activity of both receptors. Despite this breakthrough in the treatment of GIST, resistance against imatinib has been reported to be as high as 50% after the first 2 years of treatment.
Outcome of 13 consecutive patients with relapsed or metastasized GIST who were treated with imatinib was analyzed.
Mean duration of treatment was 53.5 months. Four patients developed progressive disease and died after a mean treatment time of 31 months in spite of increase of imatinib dosages to 800 mg daily. Two patients (23%) developed a progressive disease after 46 months or 52 months of treatment. Two patients had a stable disease and five had a partial response. The overall progression rate was 46%, the mean survival time since primary diagnosis was 85.8 months.
From our experience, frequency of resistance development to imatinib may be below that given in the literature (50% after 2 years). Individual treatment in specialized centers may improve compliance.
European journal of gastroenterology & hepatology 05/2009; 21(7):819-23. · 1.66 Impact Factor
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ABSTRACT: The morphological diversity of gastrointestinal stromal tumours (GISTs) is well appreciated. The aim of this study was to shed light on the molecular pathogenesis of GISTs displaying a distinct biphasic histomorphological pattern, which is poorly understood.
Six biphasic gastric GISTs (four high, one intermediate and one low risk for aggressive behaviour) were studied by histological, immunohistochemical, molecular and comparative genomic hybridization methods. The different tumour components were designated as primary and secondary compartments, based on cellularity and mitotic index. In addition, metastases from two patients were analysed separately. According to the classification of Miettinen et al., four biphasic histomorphological patterns were seen: (i) sclerosing spindle cell/dyscohesive or paraganglioma-like epithelioid (n = 2); (ii) sarcomatous spindle cell/pleomorphic sarcomatous spindle cell (n = 1); (iii) sarcomatous spindle cell/sarcomatous epithelioid (n = 2); and (iv) sclerosing epithelioid/hypercellular epithelioid/sarcomatous epithelioid (n = 1) morphology. In each case, both tumour compartments revealed the same KIT (n = 5) or platelet-derived growth factor receptor-alpha (n = 1) mutation, as well as common chromosomal imbalances reflecting their common clonal origin. Additional chromosomal imbalances were detected in the secondary tumour compartments and their respective metastases.
Our results indicate that the intratumoral phenotypic diversity in GIST reflects histomorphological progression, which is associated with higher chromosomal instability, irrespective of the primary mutation.
Histopathology 03/2009; 54(3):295-302. · 3.08 Impact Factor
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ABSTRACT: Little is known about the molecular cytogenetic changes in cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma, and on the prognostic significance of chromosomal imbalances in hepatocellular carcinoma. Seventy-eight cases of primary liver cancer with available median follow-up of 16.5 months, including 49 hepatocellular carcinomas, 22 cholangiocarcinomas, and 7 combined hepatocellular-cholangiocarcinomas, were examined by comparative genomic hybridization. In hepatocellular carcinoma, the most frequent changes were +8q (54%), -8p (54%), and +1q (42%), followed by -6q (35%), -4q (33%), -13q (29%), -14q (25%), -16q (19%), -17p (19%), +17q (17%), and +20q (15%). In comparison, cholangiocarcinoma had more gains, losses, and breakpoints than hepatocellular carcinoma or combined hepatocellular-cholangiocarcinoma, specifically more frequently -6q (91%), -3p (68%), -9p (55%), -14q (55%), -13q (45%), +1q (41%), +7q (36%), +7p (32%), and +8q (32%). Combined losses at 6q and 3p appeared to be highly characteristic for cholangiocarcinoma. In contrast, combined hepatocellular-cholangiocarcinoma shared frequent +1q (71%), +8q (57%), and -8p (57%) with hepatocellular carcinoma, but a tendency for higher numbers of imbalances with cholangiocarcinoma. Overall, higher numbers of changes, breakpoints, or gains appeared to carry unfavorable prognostic value among hepatocellular carcinomas, with higher numbers of gains retaining prognostic value among R0-resected hepatocellular carcinomas. Cholangiocarcinoma is characterized by combined losses at 6q and 3p and a tendency for chromosomal instability. On the other hand, combined hepatocellular-cholangiocarcinoma may share similar chromosomal changes with both hepatocellular carcinoma and cholangiocarcinoma, as reflected by common hepatocellular carcinoma-like +8q, +1q, and -8p and a tendency for cholangiocarcinoma-like chromosomal instability. In hepatocellular carcinoma, higher number of gains may prove an adverse prognostic parameter.
Human pathology 03/2009; 40(6):834-42. · 3.03 Impact Factor
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ABSTRACT: We present the very unusual case of a young woman suffering from a brain tumor 22 years after a stage IV spinal neuroblastoma as an infant, demonstrating the difficulties of differentiating late neuroblastoma relapse from secondary supratentorial primitive neuroectodermal tumor (sPNET). Lacking specific immunohistochemical features, the first cerebral tumor at the age of 21 was regarded as sPNET, and we pursued a therapeutic approach consisting of neurosurgical resection as well as irradiation and high-dose alkylator-based chemotherapy according to the HIT2000 protocol. Two years later the patient suffered from a diffusely infiltrating local recurrence, changing its imaging appearance as well as its immunohistochemical characteristics, now revealing disseminated positivity for neuron-specific enolase and neural cell adhesion molecule. Moreover, the lack of PNET-specific translocations (EWS/FLI1 gene fusion) in both brain tumors as well as the development of hepatic metastases was more compatible with the diagnosis of a very late relapse 22 years after initial stage IV spinal neuroblastoma.
Pediatric Neurosurgery 02/2009; 45(1):61-8. · 0.70 Impact Factor
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ABSTRACT: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. They are regarded as having relatively uniform histology, although their potential for malignant behavior varies. Despite a strong promoting role of tumor-infiltrating innate immune cells in neoplastic progression, the presence of immune cells in GISTs has not yet been studied.
A total of 47 untreated, c-kit-positive primary GISTs were immunohistochemically analyzed to distinguish histiocytic and dendritic cells (DCs) (KIM-1P, fascin, and CD68) from cells of lymphoplasmacellular origin (CD3, CD20, and CD56). Furthermore, the gene expression of proinflammatory cytokines was characterized by real-time, reverse transcription-PCR analysis of total RNA extracted from frozen tissue samples.
KIM-1P+ cells were the dominant immune cells (851+/-295 cells/mm2) and were scattered among the tumor cells. Most of the KIM-1P+ cells showed cellular projections characteristic of DCs. Fascin positivity identified a subgroup of DCs. In comparison to KIM-1P+ cells, there were significantly fewer CD68+ macrophages (196+/-217 cells/mm2). CD3+ T cells were the dominant lymphocytes (201+/-331 cells/mm2), whereas B cells (60+/-126 cells/mm2) were few. On transcriptional level, a concomitant gene expression of cytokines for the classical acute phase cytokines TNF-alpha and IL-6 was missing, thus supporting the rather innate status of immune cells.
GISTs contain, beside T lymphocytes, a high number of monocyte-derived cells, which we suggest are, at least in part, immature DCs. Together with the lack of gene expression of inflammatory cytokines in tumor tissue our results point to a possible 'symbiotic relationship' between the tumor and the local immune cells.
European Journal of Gastroenterology & Hepatology 05/2008; 20(4):327-34. · 1.76 Impact Factor
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ABSTRACT: In gastrointestinal stromal tumors (GISTs), mutually exclusive gain-of-function mutations of KIT and PDGFRA are associated with different mutation-dependent clinical behavior. Taking into account the well-known different clinical behavior of GISTs from the stomach or the intestine, the aim of the current study is to evaluate the mutation- and site-dependent effects on mRNA and protein expression of KIT and PDGFRA in a large series of primary GISTs. Fresh-frozen tissue of 53 primary GISTs from gastric (75%) or intestinal (25%) sites were analyzed for mutation of KIT or PDGFRA using direct sequencing. Furthermore, KIT and PDGFRA mRNA and protein expression were determined using quantitative RT-PCR and quantitative densitometric evaluation of Western blot data. Each tumor either had a mutation of KIT (79%) or PDGFRA (21%). All GISTs with PDGFRA mutation were from gastric sites. Mutation-dependently, GISTs with KIT mutation had a significantly higher expression of KIT and at the same time a significantly lower expression of PDGFRA compared to GISTs with PDGFRA mutation. Site-dependently, gastric GISTs had a significantly higher expression of PDGFRA and a significantly lower expression of KIT compared to intestinal GISTs. Additionally, even if the KIT-mutated GISTs alone were considered, a significantly higher expression of PDGFRA could be observed in gastric than in intestinal tumors. We also found a significant correlation between a higher protein expression of PDGFRA and longer disease-free survival. The correlation of gastric site and PDGFRA mutation with higher PDGFRA expression and longer disease-free survival suggests different regulatory roles of KIT and PDGFRA gene expression on the control of cell proliferation, and, thereby on clinical behavior. The higher PDGFRA expression in gastric GISTs possibly contributes to the well-known site-dependent clinical behavior.
Modern Pathology 11/2007; 20(10):1103-11. · 4.79 Impact Factor
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Ludmila Matyakhina,
Thalia A Bei,
Sarah R McWhinney,
Barbara Pasini,
Silke Cameron, Bastian Gunawan,
Sotirios G Stergiopoulos,
Sosipatros Boikos,
Michael Muchow,
Amalia Dutra, [......],
Elias Campo,
Maria C Cid,
Fulgencio Gomez,
Rolf C Gaillard,
Guillaume Assie,
Laszlo Füzesi,
Bora E Baysal,
Charis Eng,
J Aidan Carney,
Constantine A Stratakis
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ABSTRACT: Carney triad (CT) describes the association of paragangliomas (PGLs) with gastrointestinal stromal tumors (GISTs) and pulmonary chondromas. Inactivating mutations of the mitochondrial complex II succinate dehydrogenase (SDH) enzyme subunits SDHB, SDHC, and SDHD are found in PGLs, gain-of-function mutations of c-kit (KIT), and platelet-derived growth factor receptor A (PDGFRA) in GISTs.
Our objective was to investigate the possibility that patients with CT and/or their tumors may harbor mutations of the SDHB, SDHC, SDHD, KIT, and PDGFRA genes and identify any other genetic alterations in CT tumors.
Three males and 34 females with CT were studied retrospectively. We sequenced the stated genes and performed comparative genomic hybridization on a total of 41 tumors.
No patient had coding sequence mutations of the investigated genes. Comparative genomic hybridization revealed a number of DNA copy number changes: losses dominated among benign lesions, there were an equal number of gains and losses in malignant lesions, and the average number of alterations in malignant tumors was higher compared with benign lesions. The most frequent and greatest contiguous change was 1q12-q21 deletion, a region that harbors the SDHC gene. Another frequent change was loss of 1p. Allelic losses of 1p and 1q were confirmed by fluorescent in situ hybridization and loss-of-heterozygosity studies.
We conclude that CT is not due to SDH-inactivating or KIT- and PDGFRA-activating mutations. GISTs and PGLs in CT are associated with chromosome 1 and other changes that appear to participate in tumor progression and point to their common genetic cause.
Journal of Clinical Endocrinology & Metabolism 09/2007; 92(8):2938-43. · 6.50 Impact Factor
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ABSTRACT: In gastrointestinal stromal tumors (GISTs), mutually exclusive gain-of-function mutations of KIT and PDGFRA are associated with different mutation-dependent clinical behavior. Taking into account the well-known different clinical behavior of GISTs from the stomach or the intestine, the aim of the current study is to evaluate the mutation- and site-dependent effects on mRNA and protein expression of KIT and PDGFRA in a large series of primary GISTs. Fresh-frozen tissue of 53 primary GISTs from gastric (75%) or intestinal (25%) sites were analyzed for mutation of KIT or PDGFRA using direct sequencing. Furthermore, KIT and PDGFRA mRNA and protein expression were determined using quantitative RT–PCR and quantitative densitometric evaluation of Western blot data. Each tumor either had a mutation of KIT (79%) or PDGFRA (21%). All GISTs with PDGFRA mutation were from gastric sites. Mutation-dependently, GISTs with KIT mutation had a significantly higher expression of KIT and at the same time a significantly lower expression of PDGFRA compared to GISTs with PDGFRA mutation. Site-dependently, gastric GISTs had a significantly higher expression of PDGFRA and a significantly lower expression of KIT compared to intestinal GISTs. Additionally, even if the KIT-mutated GISTs alone were considered, a significantly higher expression of PDGFRA could be observed in gastric than in intestinal tumors. We also found a significant correlation between a higher protein expression of PDGFRA and longer disease-free survival. The correlation of gastric site and PDGFRA mutation with higher PDGFRA expression and longer disease-free survival suggests different regulatory roles of KIT and PDGFRA gene expression on the control of cell proliferation, and, thereby on clinical behavior. The higher PDGFRA expression in gastric GISTs possibly contributes to the well-known site-dependent clinical behavior.Keywords: KIT, PDGFRA, GIST, mRNA expression, protein expression, qRT–PCR
Modern Pathology 08/2007; 20(10):1103-1111. · 4.79 Impact Factor
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ABSTRACT: We describe two newly established malignant mesothelioma (MM) cell lines derived from a pleural effusion of a male. One cell line, designated as MM-Z03E, reveals an epithelioid cobblestone morphology, while the second one, designated as MM-Z03S and subcloned after in vivo selection, exhibits a sarcomatoid storiform growth pattern. Both cell lines showed the immunologic profile characteristic for MM (i.e., expression of cytokeratin, CK18, calretinin, and vimentin in both phenotypes). Cytogenetics, multicolor fluorescence in situ hybridization, comparative genomic hybridization, and oligonucleotide array CGH were performed on both cell lines. Aberrations shared by both cell lines included chromosomal losses of 1q34 approximately qter, 4, 9p, 10p, 13, 14, 16q, 18, and 22, as well as a complex structural aberration involving chromosome 17. Aberrations exclusive to MM-Z03E included gains of 3q11q27 and 5p, while gain of 9q and losses of 3q27qter, 11q, and 18 in MM-Z03S were exclusive to MM-Z03E. Both cell lines were able to develop solid transplant tumors in nude mice within 16 weeks, and immunophenotyping of tumor xenografts revealed an overall retained expression profile of the markers used. Remarkably, one xenograft from MM-Z03E revealed overexpression of p53 and widely invasive growth. In conclusion, both cell lines are useful in vivo and in vitro model systems to study the underlying genetic mechanisms of biphasic differentiation in MM, which can be of certain value considering the increasing relevance of assessing MM tumor biology for the clinical management of this disease.
Cancer Genetics and Cytogenetics 08/2007; 176(1):35-47. · 1.39 Impact Factor
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ABSTRACT: Nontraumatic adrenal hemorrhage in adults is uncommon and unexpected in the context of intracranial surgery. The authors report on a patient in whom hemodynamically relevant retroperitoneal bleeding developed within hours after an otherwise uneventful operation for a falcine meningioma. In this brief report they seek to draw attention to this rare but life-threatening complication, because rapid diagnosis can be life-saving.
Journal of Neurosurgery 07/2007; 106(6):1086-8. · 2.96 Impact Factor
