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B Bjerkehagen

Publications and source records attributed to B Bjerkehagen.

18 recordsLinked to original sources
PubMed2006

Primary spinal chondrosarcoma: radiologic findings with pathologic correlation.

PURPOSE: To describe the radiologic appearance of the four types of primary spinal chondrosarcoma (CHS) (conventional intramedullary, juxtacortical, clear cell, and mesenchymal) and to correlate with histopathologic findings. MATERIAL AND METHODS: A retrospective review was carried out of 5 patients with histopathologically confirmed primary spinal CHS; 3 F and 2 M ranging in age between 27 and 66 years (mean 40.2; median 39). Charts, conventional radiographs, computed tomography scans, and magnetic resonance images were reviewed. All the patients underwent surgical excision, followed by postoperative chemotherapy (1 patient) and radiotherapy (3 patients). Follow-up was available for all patients but one. The mean follow-up was 42 months (14-120 months). Histopathological specimens for all patients were available for review. RESULTS: Vertebral column distribution was 3 thoracic (60%), 1 cervical (20%), and 1 lumbar (20%). Neurological deficits were present in 3 (60%) cases. The radiological appearance of the four types of primary spinal CHS varies with specific lesion type. Imaging findings suggest diagnosis of the conventional intramedullary and juxtacortical types. While the clear cell and mesenchymal types show some distinctive features, these do not allow confident radiologic diagnosis. CONCLUSION: The radiologist must be aware of imaging features of these tumors in order to improve diagnostic accuracy, treatment planning, and prognosis.

Adult↗
PubMed2002

Characterization of supernumerary rings and giant marker chromosomes in well-differentiated lipomatous tumors by a combination of G-banding, CGH, M-FISH, and chromosome- and locus-specific FISH.

Supernumerary ring chromosomes and/or giant marker chromosomes are often seen in soft-tissue tumors of low-grade or borderline malignancy, such as well-differentiated liposarcomas or atypical lipomas. Classic cytogenetic banding techniques have proved insufficient to identify the genomic composition and structure of such rings and markers, but fluorescent in situ hybridization (FISH) studies have shown that they consist mainly of amplified material from chromosome 12, more specifically from bands 12q13-->q15. We have used the new FISH-based screening techniques comparative genomic hybridization (CGH) and multicolor-FISH (M-FISH) in combination with G-banding and analysis by chromosome- and locus-specific fluorescent in situ probes to examine in detail the karyotypic characteristics of 22 lipomatous tumors, most of them classified histologically as well-differentiated liposarcomas, selected because they had been shown to harbor rings and/or marker chromosomes. M-FISH, in contrast to G- banding, was found to be informative with regard to the chromosomal origin of the rings and other markers present, whereas CGH and hybridizations with locus-specific probes helped identify which subchromosomal regions were involved. We found that chromosome bands 12q15-->q21 were always gained, with 12q15-->q21 being amplified (i.e., a green-to-red ratio >2 by CGH) in 14 of 22 tumors. In three tumors, two distinct but close amplicons in 12q could be identified, corresponding to bands 12q13-->q15 and 12q21. The genomic segment 1q21-->q23 was gained in 12 cases, reaching the level of amplification in seven. Bands 6q24 and 7p15, whose pathogenetic involvement in liposarcomas has not been reported previously, were gained in three cases each. In addition, the rings and giant markers often contained interspersed sequences from several other chromosomes that did not give an equally clear impression of being nonrandomly involved.

Biomarkers, Tumor↗
PubMed2001

Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas-a possible mechanism for altering the nm23-H1 activity.

PRUNE, the human homologue of the Drosophila gene, is located in 1q21.3, a region highly amplified in human sarcomas, malignant tumours of mesenchymal origin. Prune protein interacts with the metastasis suppressor nm23-H1, but shows impaired affinity towards the nm23-H1 S120G mutant associated with advanced neuroblastoma. Based on these observations, we previously suggested that prune may act as a negative regulator of nm23-H1 activity. We found amplification of PRUNE in aggressive sarcoma subtypes, such as leiomyosarcomas and malignant fibrous histiocytomas (MFH) as well as in the less malignant liposarcomas. PRUNE amplification was generally accompanied by high mRNA and moderate to high protein levels. The sarcoma samples expressed nm23-H1 mostly at low or moderate levels, whereas mRNA and protein levels were moderate to high in breast carcinomas. For the more aggressive sarcoma subtypes, 9/13 patients with PRUNE amplification developed metastases. A similar situation was observed in all breast carcinomas with amplification of PRUNE. Infection of NIH3T3 cells with a PRUNE recombinant retrovirus increased cell proliferation. Possibly, amplification and overexpression of PRUNE has the same effect in the tumours. We suggest that amplification and overexpression of PRUNE could be a mechanism for inhibition of nm23-H1 activity that affect the development or progression of these tumours.

3T3 Cells↗
PubMed2001

Dedifferentiation of a well-differentiated liposarcoma to a highly malignant metastatic osteosarcoma: amplification of 12q14 at all stages and gain of 1q22-q24 associated with metastases.

Well-differentiated liposarcomas (WDLPS), especially those located in the retroperitoneum, may occasionally undergo dedifferentiation. Although this process is associated with a more aggressive clinical course, dedifferentiated liposarcomas rarely produces metastases. The case reported here is rather uncommon: A retroperitoneal WDLPS gave lung metastases that were diagnosed as highly malignant osteosarcomas. We used comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), and Southern blot analyses to characterize the copy number changes and genetic aberrations occurring at different stages of the disease. In the primary tumor, the only detectable aberration was amplification of 12q13-q14, which was present only in a fraction of the cells and revealed by FISH analysis. High-level amplification of 12q13-q14, involving CDK4, MDM2, and HMGIC, was seen both in the relapse and the metastases. The second most common change, gain or high-level amplification of 1q22-q24, was detectable by CGH only in the osteogenic metastases, as was loss of the distal 2q. FISH analyses revealed considerable heterogeneity in the samples, and the percentage of cells showing aberrations was significantly higher in the metastatic samples. In particular, increased copy numbers of 789f2, a marker for 1q21 amplification in sarcomas, was observed in more than 65% of the cells in the metastatic samples, but in less than 10% of the cells from the recurrent samples. These observations could indicate that 1q amplification, in particular, may be indicative of a more malignant phenotype and ability of metastasis in WDLPS, as has also been suggested by others.

Adult↗
PubMed2001

A well-differentiated liposarcoma with a new type of chromosome 12-derived markers.

Well-differentiated liposarcomas (WDLPS) are cytogenetically characterized by the presence of supernumerary ring or giant rod marker chromosomes. These supernumerary chromosomes are composed of amplified sequences from chromosome 12 (12q14 approximately 15) in association with amplified segments from various other chromosomes, and contain alterations of the alpha satellite sequences. We report a case of WDLPS of the lipoma-like and sclerosing subtype that contains a novel type of supernumerary marker chromosome. Instead of rings or giant rods, these cells had three apparently identical copies of a subtelocentric supernumerary marker with a size and shape similar to C-group chromosomes. Fluorescence in situ hybridization analysis revealed that the markers were composed of amplified material from 12q14 approximately 15, including the genes MDM2 and CDK4. Similar to the rings and giant rods observed in other WDLPS cases, these unusual markers had no alpha satellite repeats at the primary constriction site, but centromeric activity could be demonstrated by using anti-centromere protein C antibodies. These findings show that the supernumerary markers of WDLPS may be variable in size and shape, but consistently share the same genomic structure, specifically 12q amplified sequences together with centromere alterations, and underline the importance of molecular methods in the diagnosis of adipose tissue tumors.

Aged↗
PubMed2000

Frequent loss of 9p21 (p16(INK4A)) and other genomic imbalances in human malignant fibrous histiocytoma.

To search for new recurrent genetic aberrations in malignant fibrous histiocytoma (MFH), a combination of conventional cytogenetic, comparative genomic hybridization (CGH), and Southern blot analyses was applied to a series of 34 tumors. Cytogenetic analysis revealed the presence of multiple structural and numerical aberrations, including marker chromosomes, telomeric associations, double minutes, and ring chromosomes. The most frequent genomic imbalances in this series of neoplasms as detected by CGH were gains of 1q21-q22 (69%), 17q23-qter (41%), and 20q (66%), and losses of 9p21-pter (55%), 10q (48%), 11q23-qter (55%), and 13q10-q31 (55%). Southern blot analyses with p16(INK4A) (CDKN2A; 9p21) and RB1 (13q14) probes provided clear indications for frequent deletions of these tumor suppressor genes, and as such, substantiated the CGH results. Additionally, examination of the TP53 and MDM2 genes showed frequent loss and amplification, respectively. These data indicate that genes involved in the RB1- and TP53-associated cell cycle regulatory pathways may play prominent roles in the development of human MFH.

Blotting, Southern↗
PubMed2000

[Puncture cytology].

Limited public medical resources make it important to consider any diagnostic test which is inexpensive and reliable and without major side effects. The presented data are based on retrieval from the medical databases Medline and Cancerline, as well as the authors' clinical experience. The role of fine needle aspiration cytology for the diagnosis of solid and non-solid tumours is well established in the literature. The technique is simple and cost-effective and without major side effects. The sensitivity and specificity concurs that of histology in different tumours and may reduce the need for histopathology. In this review we discuss the combined use of fine needle aspiration cytology and modern immunocytochemistry and molecular techniques which may enhance diagnostic precision. We present the role of ancillary techniques which may prevent unnecessary extensive examinations and influence the therapeutic management of the patient.

Biopsy, Needle↗
PubMed1999

Fusion of the RBP56 and CHN genes in extraskeletal myxoid chondrosarcomas with translocation t(9;17)(q22;q11).

Although most extraskeletal myxoid chondrosarcomas (EMC) are cytogenetically characterized by the translocation t(9;22)(q22;q12), another subset has recently been identified carrying a t(9;17)(q22;q11). Whereas the t(9;22) is known to result in fusion of the CHN (TEC) gene from 9q22 with the EWS gene from 22q12, creating a chimeric EWS/CHN, the genes involved in the t(9;17) of EMC are unknown. We examined two EMC with t(9;17)(q22;q11) and found that the CHN gene was recombined with the RBP56 gene from 17q11 to generate a chimeric RBP56/CHN. RBP56 has not previously been shown to be involved in tumorigenesis but it encodes a putative RNA-binding protein similar to the EWS and FUS (TLS) proteins known to play a pathogenetic role in several sarcomas. The presence of the RBP56/CHN chimeric gene in EMC with t(9;17)(q22;q11) shows that the N-terminal parts of EWS and RBP56 have similar oncogenic potential making them pathogenetically equivalent in oncoproteins arising from fusions with certain transcription factors.

Amino Acid Sequence↗
PubMed1999

Extraskeletal myxoid chondrosarcoma: multimodal diagnosis and identification of a new cytogenetic subgroup characterized by t(9;17)(q22;q11).

Extraskeletal myxoid chondrosarcoma is a rare malignant soft tissue tumour that can be difficult to diagnose correctly, especially preoperatively. We describe four cases of extraskeletal myxoid chondrosarcoma of the extremities diagnosed by a multimodal approach. The cytological examination of fine-needle aspirates showed small and round, mildly pleomorphic cells lying in sheets and cords, but also dispersed within a myxoid and metachromatic intercellular substance. Histological, electron microscopic and immunocytochemical examination also yielded findings compatible with the diagnosis of extraskeletal myxoid chondrosarcoma. Cytogenetic analysis demonstrated a t(9;22)(q22;q12) in two tumours and a t(9;17)(q22;q11) in the third and fourth. The translocation t(9;22)(q22;q12) has been described repeatedly in extraskeletal myxoid chondrosarcoma but never in other tumours; hence, the detection of this pathognomonic chromosome abnormality in short-term cultured cells from fine-needle aspirates verified the diagnosis in two of the cases. The t(9;17)(q22;q11) found in the last two cases probably represents a new cytogenetic subgroup of extraskeletal myxoid chondrosarcoma as it, too, is unknown in other contexts. The multimodal approach taken in these four cases enabled a definite diagnosis of a rare malignant tumour whose cytological and histological features alone are usually not sufficiently distinct to rule out other differential diagnostic possibilities.

Aged↗
PubMed1999

Combined RxFISH/G-banding allows refined karyotyping of solid tumors.

Chromosome banding analysis of solid tumors often yields incomplete karyotypes because of the complex rearrangements encountered. The addition of fluorescence in situ hybridization (FISH) methods has helped improve the accuracy of solid tumor cytogenetics, but the absence of screening qualities from standard FISH approaches has proved a severe limitation. We describe the cytogenetic analysis of ten solid tumors using G-banding followed by cross-species color banding (RxFISH), a FISH-based screening technique giving a chromosome-specific banding pattern based on the genomic homologies between humans and gibbons. The addition of RxFISH analysis in all cases led to the identification of previously unidentified intra- as well as interchromosomal rearrangements, thus giving a much more certain and detailed karyotype. In two gastric stromal sarcomas, a tumor type for which no cytogenetic data were hitherto available, numerical chromosomal aberrations dominated, but one of the tumors also carried an unbalanced 7;17-translocation with the same breakpoint in chromosome 17 as that seen in endometrial stromal sarcomas.

Chromosome Aberrations↗
PubMed1998

Synovial sarcoma. Evaluation of prognosis with emphasis on the study of DNA ploidy and proliferation (PCNA and Ki-67) markers.

Controversy still exists regarding the validity of parameters commonly used in the evaluation of prognosis of patients with synovial sarcoma (SS). Forty-nine cases of previously untreated primary SS (23 females and 26 males, ranging in age from 7 to 81, with 31 tumors located in the lower extremity, 8 at the upper extremity and 10 at the trunchus), without regional lymph-node or distant metastases were studied. We investigated the relationship between (flow and image) DNA cytometry, proliferation activity, clinicopathologic parameters, and relapse-free and overall survival of the patients. The prognostic value of gender, age, duration of symptoms, location, compartmentalization, size, adequacy of surgical margins, residual tumor, adjuvant therapy, histologic subtype, extent of necrosis, glandular differentiation, calcification, and extent of hemangiopericytic areas, mitotic rate, amount of mast cells, blood vessel invasion, histologic (UICC and NCI) grades, DNA ploidy, percentage of cells in S and S+G2 phases, PCNA and Ki-67 labeling indices (LI), and TNM (UICC) stage of the tumors, were evaluated by univariate and multivariate (Cox hazard model) analyses. Short duration of symptoms (<12 months), biphasic SS, scarcity of mast cells (<10/10 HPF), high mitotic rate (> or =10/10 HPF), high histologic grade (grade 3), high PCNA-LI (> or =20%), high Ki-67-LI (> or =10%), DNA aneuploidy, and advanced TNM stage (stage III) were features associated with significantly shorter relapse-free and overall 5-year survival rates in the univariate analyses. Scarcity of mast cells, high mitotic rate, or high PCNA-LI were significant predictors of poor survival, in addition to TNM stage in the multivariate analyses. The amount of mast cells was inversely correlated with mitotic rate and PCNA-LI. Scarcity of mast cells, high mitotic rate, or high PCNA-LI are factors associated with poor prognosis, in addition to advanced TNM stage in patients with localized SS.

Adolescent↗
PubMed1997

Synovial sarcoma: immunohistochemical expression of P-glycoprotein and glutathione S transferase-pi and clinical drug resistance.

Our purpose was to study the role of the expression of P-glycoprotein (Pgp) and glutathione S transferase-pi (GST-pi) in predicting the response to chemotherapy, relapse-free interval, and survival of patients with synovial sarcoma (SS). Thirty-seven cases of primary SS, without regional lymph node or distant metastases, were studied. There were 17 females and 20 males, ranging in age from 7 to 81 years (median, 31 years) with tumors located in the lower extremity (n = 24) upper extremity (n = 5) and trunchus (n = 8). The cases were retrospectively studied without knowledge of clinical course to compare the immunohistochemical expression of Pgp and GST-pi, flow cytometry parameters (ploidy and % of cells in S+G2 phases), and PCNA and Ki-67 labeling of primary tumors before any therapy, with that observed in local recurrences and metastases after chemotherapy. The relationship of the aforementioned parameters with clinicopathological features (gender, age, and histo-blood group of the patients, size, location, histological subtype. TNM stage, and clinical response to chemotherapy of the tumors) was also evaluated. Results revealed that Pgp and GST-pi were expressed in 29.7% and 40.5% of the cases, respectively. In 48.6% of the tumors there was expression of a least one of the drug resistance markers. The markers were coexpressed in 25.0% of the tumors. The prevalence of Pgp expression was lower, but not significantly, in stage I-II (17.6%) than in stage III (40.0%) tumors, and also in cases without clinical progression (16.7%), than in cases with (36.0%). No such differences were observed for GST-pi expression. Pgp and GST-pi expressions were significantly associated with biphasic SS and were particularly noticeable in solid/glandular areas of biphasic SS. The expression of the drug resistance markers was not significantly associated with gender, age, and histo-blood group of the patients, dimension, location, and proliferative activity of the tumors; it was also not significantly related to relapse-free interval and survival of the patients. The expression of Pgp and GST-pi was not significantly associated either to response to chemotherapy or influenced by chemotherapy. We conclude that Pgp and GST-pi expressions are not good predictors response to of the chemotherapy in patients with localized SS. Other drug resistance mechanisms may be active in SS.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Immunohistochemical profile of synovial sarcoma with emphasis on the epithelial-type differentiation. A study of 49 primary tumours, recurrences and metastases.

The relationship between biphasic (BSS) and monophasic (MSS) subtypes of synovial sarcoma (SS) as well as the relationship between cells of solid/glandular areas and the spindle cells of BSS remain controversial. In order to further evaluate the immunohistochemical phenotype of SS we studied 34 primary tumours (15 BSS; 19 MSS), 7 recurrences (4 from primary BSS; 3 from primary MSS) and 8 metastases (7 BSS; one MSS), using several antibodies (EMA, CEA, keratins 1, 4, 5/6, 7, 8, 13, 18, 19, 20, vimentin, collagen IV and laminin) that work in paraffin-embedded material. Spindle cells outside solid/glandular areas of BSS and in MSS showed immunoreactivity for keratins 5/6, 7, 8, 18 and 19. The transition of solid/glandular areas to surrounding spindle cells also showed keratin staining and failed to show a distinct separation regarding the immunoreactivity for laminin and collagen IV. Peripheral cells of solid/glandular areas were immunoreactive for vimentin. No major differences were observed between immunophenotypical cell profiles of BSS and MSS, apart from the exclusive immunostaining of solid/glandular areas of BSS for keratin 13 and CEA. Downgrading of keratin and extracellular matrix antigens immunoreactivity was observed when primary tumours were compared to recurrent and/or metastatic tumours of both subtypes (MSS and BSS). We conclude that SS should be regarded as carcinomas of soft tissues with an immunohistochemical phenotype depending on the degree of epithelial differentiation: spindle cells (MSS and BSS) predominantly expressing simple keratins, and poorly differentiated (solid/glandular) as well as well-differentiated (glandular) areas (BSS) expressing, in addition, complex epithelial-type keratins.

Adolescent↗
PubMed1994

Transitional cell carcinoma of the renal pelvis and its expression of p53 protein, c-erbB-2 protein, neuron-specific enolase, Phe 5, chromogranin, laminin and collagen type IV.

Expression of p53 protein, c-erbB-2 protein, neuron-specific enolase (NSE), Phe 5, chromogranin, laminin and collagen type IV was studied by immunohistochemistry in formalin-fixed and paraffin-embedded specimens from 20 patients with renal pelvic carcinoma. Positive membrane-bound c-erbB-2 staining was not found in any case. Two tumors stained for p53 protein. Focal immunoreactivity for laminin was present in 55% and for collagen type IV in 80%. 25% of the cases were NSE positive. None of the tumors stained for Phe 5 or chromogranin. The results were compared with the clinical outcome and the immunohistological findings of p53 protein and c-erbB-2 protein in 13 cases of bladder carcinoma in the same patient group. Four of the thirteen bladder cancer specimens, but only 2 of the 20 renal pelvic cancer specimens, expressed p53 protein. As for renal pelvic carcinoma, c-erbB-2 protein was not expressed in bladder carcinoma. We conclude that p53 gene abnormalities may be of importance in the development of carcinoma in the renal pelvis and urinary bladder, but c-erbB-2 protein expression does not play a major role.

Adult↗
PubMed1992

Carcinoma of the renal pelvis. Experience of 80 cases.

The clinical course and association with other urothelial carcinomas was studied in 80 patients with carcinoma of the renal pelvis. At the time of diagnosis macroscopic haematuria was the most common symptom. Urography and retrograde pyelography gave the most accurate diagnoses. Sixty-eight patients (85%) had transitional cell carcinomas, 39 had a history of another urothelial carcinoma either before or after the diagnosis of the renal tumour, usually in the urinary bladder. A previous urothelial carcinoma together with a small renal tumour were predictive of the subsequent development of another urothelial tumour. Regular cystoscopy is recommended during follow-up because of the short observed interval between the development of carcinoma of the renal pelvis and a subsequent urothelial malignancy. The overall five-year survival was 20%. Survival did not depend on the operation, but was significantly related to the extent of locoregional or distant metastases at the time of diagnosis. Patients with such renal tumours that were preceded by or associated with other urothelial carcinomas had a more favourable median survival (42 months) than patients whose renal tumour was their first urothelial carcinoma (19 months).

Adenocarcinoma↗
PubMedDate not supplied

The ultrastructural spectrum of synovial sarcomas: a study of the epithelial type differentiation of primary tumors, recurrences, and metastases.

Synovial sarcomas (SS) are malignant soft tissue tumors of unknown origin. Their classification as carcinomas (monophasic synovial sarcomas, MSS) or carcinosarcomas (biphasic synovial sarcomas, BSS) still raises controversy. In an attempt to settle this controversy, an ultrastructural study was undertaken of 25 primary SS (12 BSS and 13 MSS), 5 recurrences (3 BSS and 2 MSS), and 2 metastases (2 BSS) based upon precise selection of different aspects of BSS and MSS on numerous semithin sections from each case. Ultrastructural markers of epithelial type differentiation of neoplastic cells were found in every type of cellular component of SS regardless of the tumoral pattern (biphasic or not). No major differences were found between MSS and the nonglandular areas of BSS (not even regarding the presence of abortive glandular lumina). Cytoarchitectural transitions were frequently observed; these included spindle to epithelioid cell types and fascicular to solid (MSS and BSS) or fascicular to glandular (BSS) patterns. These findings support the assumption that spindle cells of SS are neoplastic and may evolve to glandular cells in SS. Based on the cytogenetic data pointing to a common pathogenesis of both phenotypes (BSS and MSS), SS may represent true carcinomas of soft tissues with a biphasic and/or monophasic pattern depending on the degree of differentiation.

Adolescent↗
PubMedDate not supplied

Proliferative activity of synovial sarcoma: an immunohistochemical evaluation of Ki-67 labeling indices of 52 primary and recurrent tumors.

The relationship between cell differentiation and proliferation in biphasic synovial sarcoma (BSS) and the connection between the two components of these tumors and monophasic synovial sarcoma (MSS) are still unknown. In this study we specifically compared the Ki-67 labeling indices (Ki-67-LI) in the solid/glandular and spindle cell components of primary BSS (n = 8) as well as the values thus obtained in primary BSS both outside clear-cut biphasic areas (n = 7) and in primary MSS (n = 23). We also compare the Ki-67-LI of primary tumors (seven BSS, seven MSS) and their respective first recurrences. We observed that the cells of the solid/glandular component of BSS proliferate significantly faster (p = 0.007) than those of spindle cell areas. No significantly different Ki-67-LI were observed in the comparison of the solid/glandular areas of BSS with the spindle/epithelioid component of BSS without clear-cut biphasia and MSS. No significant differences of Ki-67-LI were observed in the comparison of primary tumors of both subtypes with their respective first recurrences. The implications of the low proliferative activity of the spindle cell component of BSS exhibiting clear-cut biphasia, which was also confirmed in a concurrent study using anti-proliferating cell nuclear antigen/Cyclin PC10, remains to be clarified.

Adolescent↗