Biomedical subjects

K Franssila

Publications and source records attributed to K Franssila.

At least 19 recordsLinked to original sources

PubMed1999

Characterization of a novel human surface molecule selectively expressed by mature thymocytes, activated T cells and subsets of T cell lymphomas.

We have previously characterized mouse H4 (mH4), a surface glycoprotein recognized by the C398.4A monoclonal antibody. We now show that C398.4A also binds its human putative homolog (hpH4). Both hpH4 and mH4 (1) are selectively expressed by activated T cells and mature thymocytes, (2) are disulfide-linked dimers of two chains (29/37 kDa in humans, 25/29 kDa in mice), whose N-deglycosylation produces a single band at 20 - 21 kDa, and (3) display a low association with CD4 and the TCR. The expression pattern of hpH4 and its biochemical features showed that it is different from other known activation molecules, and this was confirmed when analysis of the tryptic digest of the hpH4 29-kDa band by peptide mass searching using matrix-assisted laser desorption ionization mass spectrometry did not reveal any significant homology with other molecules. In normal lymphoid tissue, hpH4 is expressed by T cells located at the periphery of lymph node germinal centers and paracortical areas. In T cell neoplasia, expression of hpH4 clusters with a subset of peripheral T cell lymphomas with a large-cell component, and with cases of angioimmunoblastic T cell lymphomas. Overall, these data provide evidence for a novel T cell activation molecule that could help in the phenotypic categorization of T cell malignancies.

Animals↗

PubMed1999

Central nervous system involvement in patients with mantle cell lymphoma.

In small cell lymphomas, central nervous system (CNS) involvement has been considered to be very rare. Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin's lymphomas consisting of small or intermediate lymphatic B-cells. It has a poorer prognosis than the other small cell lymphomas. Only a few MCL patients with CNS involvement have been reported in the literature to date. We analyzed retrospectively the incidence, clinical characteristics, and outcome of CNS involvement in 94 patients with confirmed MCL treated at one center from 1980 to 1997. Four of the 94 patients (4%) developed CNS lymphoma during the median follow-up of 51 months. The diagnosis was based on clinical, cytological and radiological findings. CNS involvement appeared at 4.6, 56, 66, or 86 months from the diagnosis of MCL. All patients had neurological symptoms and a leukemic disease; two cases were seen with a blastoid morphology. Malignant lymphatic cells were detected in spinal fluid in all cases and parenchymal infiltrations in brain in two. All patients were treated with intrathecal chemotherapy, without response. Survival time after diagnosis of CNS lymphoma ranged from 18 to 55 days. At diagnosis, no adverse prognostic factors predictive of CNS lymphoma were found. CNS involvement was associated with a progressive leukemic disease as a late event or a blastoid transformation. The prognosis of MCL patients with CNS involvement is poor.

Bone Marrow↗

PubMed1999

DNA copy number changes in thyroid carcinoma.

The genetic changes leading to thyroid cancer are poorly characterized. We studied DNA copy number changes by comparative genomic hybridization (CGH) in 69 primary thyroid carcinomas. In papillary carcinoma, DNA copy number changes were rare (3 of 26, 12%). The changes were all gains, and they were associated with old age (P = 0.01) and the presence of cervical lymph node metastases at presentation (P = 0.08). DNA copy number changes were much more frequent in follicular carcinoma (16 of 20, 80%) than in papillary carcinoma (P < 0.0001), and follicular carcinomas had more often deletions (13/20 versus 0/26, P < 0.0001). Loss of chromosome 22 was common in follicular carcinoma (n = 7, 35%), it was more often seen in widely invasive than in minimally invasive follicular carcinoma (54% versus 0%, P = 0.04), and it was associated with old age at presentation (P = 0.01). In three of the four patients with follicular carcinoma who died of cancer, the tumor had loss of chromosome 22. DNA copy number changes were found in 5 (50%) of the 10 medullary carcinomas studied. Four of these five carcinomas had deletions, and in two of them there was deletion of chromosome 22. Eleven (85%) of the thirteen anaplastic carcinomas investigated had DNA copy number changes, of which five had deletions, and one had deletion of chromosome 22. The most common gains in anaplastic carcinoma were in chromosomes 7p (p22-pter, 31%), 8q (q22-qter, 23%), and 9q (q34-qter, 23%). We conclude that DNA copy number changes are frequent in follicular, medullary, and anaplastic thyroid carcinoma but rare in papillary carcinoma when studied by CGH. Loss of chromosome 22 is particularly common in follicular carcinoma, and it is associated with the widely invasive type.

Adenocarcinoma, Follicular↗

PubMed1999

Molecular characterization of deletion at 11q22.1-23.3 in mantle cell lymphoma.

Chromosomal deletions at 11q21-23 have recently been reported to be common aberrations in mantle cell lymphoma (MCL). To characterize the structure of the deletion, we studied 41 cases of MCL by fluorescence in situ hybridization using a YAC contig, which spans the region at 11q22.1-23.3. 17 MCLs were studied using a set of 20 yeast artificial chromosomes (YACs) in a contig, and nine of these cases showed deletion of 11q22-23. The deletion spanned several megabases in all but one case, where only YAC 755b11 at 11q23.1, covering approximately a 1.6 Mb of DNA, was deleted. Analysis of additional 24 MCLs with YAC 755b11 revealed the deletion in 49% of all cases (20/41). The deleted region at 11q22.1-23.3 was discontinuous in five lymphomas and in the majority of the cases the distal breakpoint occurred between YACs 785e12 and 911f2 at 11q23.3. We conclude that the deletion of 11q22-23 and particularly the deletion of YAC 755b11 are very common in MCL and may be important in the genesis or progression of the disease.

Adult↗

PubMed1999

MIB-1 immunoreactivity correlates with blood vessel density and survival in disseminated malignant melanoma.

The purpose of our current work was to evaluate the prognostic significance of tumor cell proliferation in advanced metastatic melanomas and to investigate a possible correlation between the proliferation index and blood vessel density in metastatic tissue. Sixty patients with disseminated malignant melanoma treated with four-drug chemotherapy combined with interferon-alpha were included in this study. Proliferative activity and vascularity in metastatic tissues were examined by immunohistochemistry with anti-Ki-67 (MIB-1) and anti-CD31 antibody, respectively. A significant relationship between MIB-1 index and blood vessel number was detected (rho = 0.323, p = 0.013). In survival analysis, the overall survival and disease-free survival were significantly longer (58 and 38 vs. 38 and 17 months) for patients with low MIB-1 immunoreactivity (p = 0.012 and p = 0.023, respectively). Likewise, the low MIB-1 labeling index was associated with the prolonged survival calculated from the initiation of the chemoimmunotherapy (12 vs. 7 months, p = 0.032). In multivariate Cox's proportional hazard analysis, MIB-1 positivity was an independent prognostic factor both for overall survival and for survival after beginning of the chemoimmunotherapy (p = 0.016 and p = 0.029).

Adult↗

PubMed1999

Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease.

PURPOSE: Recent studies have suggested that lymphocyte-predominant Hodgkin's disease (LPHD) is both clinically and pathologically distinct from other forms of Hodgkin's disease, including classical Hodgkin's disease (CHD). However, large-scale clinical studies were lacking. This multicenter, retrospective study investigated the clinical characteristics and course of LPHD patients and lymphocyte-rich classical Hodgkin's disease (LRCHD) patients classified according to morphologic and immunophenotypic criteria. MATERIALS AND METHODS: Clinical data and biopsy material of all available cases initially submitted as LPHD were collected from 17 European and American centers, stained, and reclassified by expert pathologists. RESULTS: The 426 assessable cases were reclassified as LPHD (51%), LRCHD (27%), CHD (5%), non-Hodgkin's lymphoma (3%), and reactive lesion (3%); 11% of cases were not assessable. Patients with LPHD and LRCHD were predominantly male, with early-stage disease and few risk factors. Patients with LRCHD were significantly older. Survival and failure-free survival rates with adequate therapy were similar for patients with LPHD and LRCHD, and were stage-dependent and not significantly better than stage-comparable results for CHD (German trial data). Twenty-seven percent of relapsing LPHD patients had multiple relapses, which is significantly more than the 5% of relapsing LRCHD patients who had multiple relapses. Lymphocyte-predominant Hodgkin's disease patients had significantly superior survival after relapse compared with LRCHD or CHD patients; however, this was partly due to the younger average age of LPHD patients. CONCLUSION: The two subgroups of LPHD and LRCHD bore a close clinical resemblance that was distinct from CHD; the course was similar to that of comparable nodular sclerosis and mixed cellularity patients. Thorough staging is necessary to detect advanced disease in LPHD and LRCHD patients. The question of how to treat such patients, either by reducing treatment intensity or following a "watch and wait" approach, remains unanswered.

Adult↗

PubMed1999

BCL2 overexpression in diffuse large B-cell lymphoma.

Translocation (14;18)(q32;q21), which is detected in 20-30% of diffuse large B-cell lymphomas (DLBCL), is regarded as a major mechanism for BCL2 protein overexpression. Nevertheless, BCL2 overexpression is not always caused by t(14;18), because it is often detected in lymphomas without BCL2 rearrangement. Recent studies have shown that increased expression of BCL2 may also result from BCL2 gene amplification in DLBCL. Similarly, it has been speculated that the mutations of the open reading frame might cause increased expression of BCL2 by affecting the interactions of BCL2 with other proteins. The results obtained from studies on the association of BCL2 protein overexpression with survival of DLBCL are controversial, although a correlation with decreased overall survival seems to exist. However, BCL2 rearrangement does not seem to have any major association with poor prognosis, but it is difficult to assess its true impact on prognosis due to differences in treatment and follow-up, and methodologies applied to study the BCL2 rearrangement. This review summarizes the BCL2 expression studies in DLBCL and discusses the prognostic relevance of BCL2 overexpression and its mechanisms.

Animals↗

PubMed1998

Neoexpression of the epithelial adhesion complex antigens in thyroid tumours is associated with proliferation and squamous differentiation markers.

Integrin dimer alpha 6 beta 4 is a transmembrane component of an epithelial cell adhesion complex that consists of hemidesmosomes (HDs), basement membrane (BM)-associated laminin-5 (Ln-5), and anchoring filaments/type VII collagen, all of which are absent from normal thyroid follicular epithelium. In the present study, the expression of epithelial cell adhesion complex antigens in thyroid tumours was investigated using immunohistochemistry. In addition to integrin subunits alpha 6 and beta 4, immunoreactivity was found for all chains of Ln-5, alpha 3, beta 3 and gamma 2, type VII collagen and hemidesmosomal antigen, HD1, in most thyroid carcinomas associated with tumour anaplasia and papillary growth pattern and located at the border of parenchymal cells and connective tissue or blood vessel walls. In addition, a more restricted expression of bullous pemphigoid antigens 180 and 230 (BP180 and BP230), constituents of HDs, was found in some papillary and anaplastic carcinomas and atypical adenomas. Adhesion complex antigens were located to regions of cells which were immunoreactive for cytokeratin (ck)-5 and proliferating cell nuclear antigen Ki-67. The results suggest that in thyroid carcinomas, the emergence of adhesion complex antigens is associated with squamous differentiation and high proliferative activity.

Antigens, Neoplasm↗

PubMed1998

Gain of 3q and deletion of 11q22 are frequent aberrations in mantle cell lymphoma.

We used comparative genomic hybridization (CGH) to screen for DNA copy number changes in 34 specimens from 27 cases of mantle cell lymphoma (MCL). The most common gains were detected at 3q (52%), 8q (30%), and 15q (26%), whereas the most frequent losses involved 13q (41%), 1p (33%), 6q (30%), 9p (30%), and 11q (30%). The gain of 3q, with a minimal common region at 3q26.1-27, appeared in more than half of the lymphomas, suggesting the location of an important oncogene here. A common deleted region at 11q22 was found in one-third of the patients, which suggests that this region may harbor a tumor suppressor gene important in the tumorigenesis of MCL. The mean number of changes was higher in more aggressive blastoid variants of MCL than in lymphomas with typical morphology. Our results show that the chromosomal regions affected in MCL are highly consistent and are different from those seen in other types of non-Hodgkin's lymphoma.

Aged↗

PubMed1998

Mantle cell lymphoma: clinical features, treatment and prognosis of 94 patients.

Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkin's lymphoma recently recognised as a distinct disease entity. Little is known about the prognostic factors and optimal treatment of MCL. The aim of this study was to analyse retrospectively the clinical features and effect of treatment in 94 MCL patients diagnosed and treated in one centre between 1980 and 1996, and to find out different factors influencing the treatment results and prognosis. The median age of the patients was 66 years, and 77% were over 60 years old. Of the patients, 76% had advanced disease, the performance status (PS) was WHO 0-1 in 86%, and B symptoms were present in 35% of the cases. Bone marrow infiltration was found in 61% and overt leukaemia in 12% of the patients. Of the patients, 47% achieved complete remission with first- or second-line therapy. The median duration of remission, time to treatment failure (TTF), and survival were 28, 18, and 41 months, respectively. In multivariate analyses, age, stage and leukaemic disease were significantly associated with TTF, and age, stage, leukaemic disease and lactate dehydrogenase (LDH) with survival. Long-term prognosis is poor in MCL. None of the conventional chemotherapies seems curative. A prospective randomised trial should be made to evaluate the benefit of anthracycline-containing regimens in MCL.

Adult↗

PubMed1998

A multivariate analysis of tumour biological factors predicting response to cytotoxic treatment in advanced breast cancer.

The study was designed to identify factors that could predict response to chemotherapy in breast cancer. A total of 173 patients with measurable or evaluable metastatic breast cancer were enrolled in a randomized trial between November 1987 and January 1991 to receive a monthly dose of 5-fluorouracil (500 mg m(-2)), epirubicin (60 mg m(-2)) and cyclophosphamide (500 mg m(-2)) either administered in four weekly doses or in an every-4-week dose as first-line cytotoxic treatment. In 103 evaluable patients we performed a multivariate analysis of the tumour biological factors, i.e. histological grade, oestrogen receptor (ER), progesterone receptor (PR), S-phase fraction (SPF), ploidy, p53, c-erbB-2, Bcl-2 and Bax expression, which showed significance in the univariate analysis according to treatment response, time to progression (TTP) or overall survival (OS). In the univariate analysis only SPF, grade and the proapoptotic protein Bax correlated with the response to cytotoxic treatment. In the multivariate analysis SPF had the strongest correlation, followed by grade and Bax. In the univariate analysis grade, PR, Bax and Bcl-2 correlated significantly with TTP, whereas in the multivariate analysis only PR showed a statistically significant correlation. In the univariate analysis PR and Bax correlated with OS and both retained its significance in the multivariate analysis. The factors that correlated significantly with the response to cytotoxic treatment in the univariate analysis, i.e. grade, SPF and Bax, seemed to predict independently the response to treatment in the multivariate analysis also. TTP and OS could be predicted partly by the same factors, although the association was quite weak. More studies and new tumour biological factors are needed to identify the group of breast cancer patients who get the most benefit from chemotherapy.

Analysis of Variance↗

PubMed1998

Comparison of benign and malignant follicular thyroid tumours by comparative genomic hybridization.

DNA copy number changes were compared in 29 histologically benign follicular adenomas, of which five were atypical, and 13 follicular carcinomas of the thyroid by comparative genomic hybridization. DNA copy number changes were frequent in adenomas (14 out of 29, 48%). Most changes were gains, and they always involved a gain of the entire chromosome 7 (10 out of 29, 34%); other common gains involved chromosomes 5 (28%), 9 (10%), 12 (24%), 14 (21%), 17 (17%), 18 (14%) and X (17%). Losses were found only in four (14%) adenomas. Two of the five atypical adenomas had DNA copy number losses, and none had gains. Unlike adenomas, gains were rare and losses were frequent in carcinomas. A loss of chromosome 22 or 22q was particularly common in carcinomas (6 out of 13, 46%), whereas a loss of chromosome 22 was found in only two (7%) adenomas, one of which was atypical (P = 0.002). A loss of 1p was also frequent in carcinomas (31%), but gains of chromosomes 5, 7, 12, 14 or X that were common in adenomas were not found. Loss of chromosome 22 or 22q was present in six of the eight widely invasive follicular carcinomas, but in only one of the five minimally invasive carcinomas. We conclude that large DNA copy number changes are common in thyroid adenomas. These changes are strikingly different from those found in follicular carcinomas consisting of few losses and frequent gains, especially those of chromosome 7. A loss of chromosome 22 is common in widely invasive follicular carcinoma.

Adenoma↗

PubMed1998

Low number of DNA copy number changes in small lymphocytic lymphoma.

BACKGROUND AND OBJECTIVE: Small lymphocytic lymphoma (SLL) is morphologically and immunologically similar to chronic lymphocytic leukemia (CLL), and the new REAL classification refers to them as a single disease termed SLL/CLL. Recently, frequent losses in 6q, 11q and/or 13q were observed in CLL using comparative genomic hybridization (CGH). We performed CGH analyses in order to find out whether these two entities contain the same DNA copy number changes. DESIGN AND METHODS: Seventeen patients with stage IV disease and one with stage III disease were studied by CGH. CGH is based on quantitation of the fluorescence intensity of differentially labeled DNAs. For this purpose tumor DNA labeled with FITC-12dUTP and normal DNA labeled with Texas red-5dUTP were hybridized to normal metaphase chromosomes. The ratio of fluorescence intensity of hybridized tumor and normal DNA was measured using computerized image microscopy to identify over- or under-represented regions in the tumor genome. All findings were confirmed using a confidence interval of 99% with a 1% error probability. RESULTS: The most consistent finding was a gain of the entire chromosome 12 observed in three patients and a loss in 14q24 in one patient. No other changes were detected. All abnormal cases presented with stage IV disease and had bone marrow infiltration. Two 12+ cases had a leukemic disease. INTERPRETATION AND CONCLUSIONS: Our results indicate that trisomy 12 is one of the most frequent chromosomal aberrations in SLL. Losses regarded as typical of CLL were not present in SLL. This may indicate that the genetic pathways in the development of SLL/CLL in patients presenting with enlarged lymph nodes (SLL) with or without leukemia are different from those in patients presenting with leukemia (CLL) without enlarged lymph nodes.

Adult↗

PubMed1997

BCL2 overexpression associated with chromosomal amplification in diffuse large B-cell lymphoma.

Gene activation by translocation between an oncogene and an immunoglobulin heavy-chain gene, which leads to increased expression of the oncoprotein, is a well-known mechanism in the genesis of B-cell lymphomas. In contrast, the role of gene amplification in activation of oncogenes in non-Hodgkin's lymphomas is poorly characterized. To study the BCL2 amplification we performed comparative genomic hybridization (CGH), Southern blot hybridization, Western analysis, immunohistochemistry, metaphase fluorescence in situ hybridization, and chromosome analysis on 26 cases of diffuse large B-cell lymphoma (large noncleaved cell lymphoma). The gain or high-level amplification of 18q was found in eight tumors (31%) by CGH, and Southern analysis revealed BCL2 amplification in these cases, but not in the cases with normal chromosome 18 or t(14;18)(q32;q21). Western immunoblot analysis and immunohistochemistry revealed a high-level expression of BCL2 protein in the cases with BCL2 amplification and t(14;18)(q32;q21). However, translocation (14;18)(q32;q21) was not detected in any of the cases with BCL2 amplification. Therefore, our results suggest that amplification of the BCL2 gene is an important mechanism for BCL2 protein overexpression in diffuse large B-cell lymphoma.

Adult↗

PubMed1997

Spontaneous splenic rupture in two patients with a blastoid variant of mantle cell lymphoma.

Spontaneous rupture of the spleen is a rare complication of hematological malignancies, occurring most commonly in patients with acute leukemia, but it has been documented in chronic leukemias and also in lymphomas. We report two patients with histologically and immunohistochemically confirmed mantle cell lymphoma (MCL) who experienced a spontaneous splenic rupture. An 80-year-old woman and a 51-year-old man had a blastoid variant of MCL and responded poorly to conventional treatment. Both patients recovered after splenectomy. The woman died of progressive lymphoma 2 months later. An allogeneic bone marrow transplantation was performed in the man with a good initial result, but an aggressive relapse was seen only 6 months later and he died of progressive lymphoma. In view of our data, we suggest special caution when MCL is complicated by rapid progression and severe splenomegaly. Although it is a rare phenomenon, the risk of splenic rupture should be kept in mind.

Aged↗

PubMed1997

Changes in the distribution of integrins and their basement membrane ligands during development of human thyroid follicular epithelium.

Interactions between cells and basement membrane components are crucial for the regulation of epithelial cell differentiation and polarization. We have studied by immunohistochemical methods the distribution of integrin adhesion proteins and some of their basement membrane ligands in foetal (16-19 weeks) and adult thyroid follicular epithelia. A diffuse immunoreactivity for only alpha 3, alpha v and beta 1 integrins was found in foetal follicular epithelium, whereas in adult follicular epithelium these integrins were expressed basally in a polarized manner. Additionally, beta 3 integrin was seen in a more basolaterally confined manner in adult follicular epithelium. Among basement membrane components, laminin alpha 1, beta 1, gamma 1 and beta 2 chains were found in epithelial basement membranes of the foetal thyroid gland, suggestive of the presence of laminins-1 and -3. In contrast, the basement membranes of adult follicular epithelium presented a much weaker immunoreactivity for the laminin beta 2 chain. Furthermore, immunoreactivity for the laminin alpha 2 chain was occasionally seen in adult thyroid glands, apparently confined to myofibroblasts. Immunoreactivity for type IV collagen alpha 1 and alpha 2 (IV) chains was found in follicular basement membranes of foetal as well as adult thyroid gland. The results suggest that during maturation of foetal thyroid follicular epithelium a distinct polarization of integrins takes place. In mature thyroid follicular epithelium, the presumable adhesion-mediating integrin complexes are alpha 3 beta 1, alpha v beta 1 and/or alpha v beta 3 mediating adhesion to laminin-1 (alpha 1-beta 1-gamma 1) and type IV collagen trimer alpha 1(2) alpha 2 (IV).

Adult↗

PubMed1997

Predictive value of c-erbB-2, p53, cathepsin-D and histology of the primary tumour in metastatic breast cancer.

The value of various prognostic factors in breast cancer patients has been determined in a number of studies. Few reports have been published on the dependence of treatment outcome on histological and immunohistochemical characteristics in the primary tumour in patients with metastatic disease. We studied the incidence and prognostic value of histological and molecular abnormalities in the primary tumour of patients who had developed metastatic breast cancer. Eligible patients received a fluorouracil, epirubicin and cyclophosphamide (FEC) regimen either once a week or once every 4 weeks. Adequate specimens for various analyses were available from 127 patients. Median follow-up time of the patients ranged from 15 to 101 months. In this study, the histological grade of the malignancy best predicted response to chemotherapy (P < 0.0005). Most of the responses were observed in patients with grade 1 tumours; in this group, time to progression was delayed. C-erb B-2 gene amplification and oncoprotein expression had no predictive value. Neither p53 nor cathepsin-D predicted treatment outcome after chemotherapy. None of the factors had an effect on overall survival. Among breast cancer patients who received anthracycline-containing chemotherapy, response to treatment correlated with histological grade. In patients with histological grade 1 breast cancer, the time to progression was longest. However, overall survival was not affected by histological grade nor the other parameters tested. In addition to histological grade, other prognostic factors that are not included in this study need to be identified to determine which patients with metastatic breast cancer would benefit from cytotoxic treatment.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

DNA copy number changes in diffuse large B-cell lymphoma--comparative genomic hybridization study.

We studied DNA copy number changes in diffuse large B-cell lymphoma using comparative genomic hybridization analysis on 20 primary tumors and on 12 recurrent tumors excised after chemotherapy or radiotherapy. Twenty-nine (91%) of the cases showed abnormal copy number karyotypes. Chromosomal regions at X (41%), 1q (38%), 7 (31%), 3 (24%), 6p (21%), 11 (21%), 12 (21%), and 18 (21%) were most frequently gained, and the most common losses involved 6q (38%), X (21%), 1p (14%), and 8p (10%). High-level amplifications were observed at 6p23-ter, 10p12-14, 17p1l.2, 18q21-ter, and Xq22-ter, all but 18q appearing only in the recurrent tumors. Gains (median, 2; range, 0 to 10) were more frequent than losses (median, 1; range, 0 to 7; P = .0004). The median number of aberrations found in the recurrent tumors (6.5) was greater than that in the primary tumors (2; P = .01). The copy number changes found in the recurrent tumors were more random than those found in the primary tumors, which were mainly located in the most frequently affected regions. Our findings are in line with those observed using conventional cytogenetic analysis, but especially novel high-level amplifications were detected. Southern blot analysis showed BCL2 amplification, but not translocation t(14;18)(q32;q21), in cases in which a gain at 18q was detected by comparative genomic hybridization, which strongly suggests that, in addition to translocation, gene amplification is another mechanism for the overexpression of the BCL2 protein.

Adult↗