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K Franssila

Publications and source records attributed to K Franssila.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1996

Molecular diagnosis of mantle cell lymphoma in paraffin-embedded tissue.

Mantle cell lymphoma (formerly known as intermediate lymphocytic lymphoma, diffuse centrocytic lymphoma, or diffuse small cleaved lymphoma) is one of the small cell non-Hodgkin lymphoma entities that is clinically more aggressive than small lymphocytic lymphoma, and needs to be separated from it. Mantle cell lymphoma is strongly associated with the t(11;14) chromosomal translocation that rearranges the bcl-1 oncogene (PRAD-1 gene) and immunoglobulin heavy chain gene. In this study, we developed a nested polymerase chain reaction system to evaluate the t(11;14) translocation. The study material consisted of 10 mantle cell lymphomas fulfilling the criteria suggested by other authors (P. M. Banks et al. Surg Pathol 16:637, 1992). A novel nested polymerase chain reaction system was used to evaluate the bcl-1 breaks in the major translocation cluster using two successive polymerase chain reaction amplifications. This reaction yielded a background-free single product of the size of 200 to 300 base pairs in four of 10 mantle cell lymphomas. The identity of the product from the nested polymerase chain reaction was confirmed by Southern blotting followed by hybridization with a specific probe. The amplification products were also evaluated by Sst-I, Alu-I, Dde-I, and Ita-I restriction enzymes and showed different patterns of digestion reflecting individual differences between the MTC/ IgH junctions. A selection of other low-grade lymphomas, including lymphocytic, follicular, and mucosa-associated lymphoid tissue lymphoma, and hairy cell leukemia and 29 hyperplastic lymph nodes were negative. This nested polymerase chain reaction system for the t(11;14) translocation involving major translocation cluster offers a convenient specific identification for mantle cell lymphoma. However, this test has a limited diagnostic power because only about half of the mantle cell lymphomas show the bcl-1 breaks in the major translocation cluster. The test performs well in formaldehyde-fixed and paraffin-embedded material, allowing the study of large numbers of retrospective cases of mantle cell lymphomas.

Aged↗
PubMed1995

Reduced expression of proapoptotic gene BAX is associated with poor response rates to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma.

Bax is a homologue of Bcl-2 that promotes apoptosis. Bax protein levels were assessed by immunohistochemical methods in primary tumors derived from 119 women with metastatic breast cancer. These patients had received combination chemotherapy either with a once a month dosage schedule or in 4 weekly divided doses. The BAX immunostaining results were retrospectively compared with overall survival, time to tumor progression (TTP), and response, as well as several laboratory markers. Normal breast epithelium and in situ carcinomas immunostained positively for Bax. Marked reductions in Bax immunostaining were observed in 40 (34%) of 119 evaluable tumors. Reduced Bax correlated with shorter overall survival (median, 8.1 versus 15.7 months; P = 0.04), faster TTP (median, 2.0 versus 6.3 months; P = 0.009), and failure to respond (complete response, partial responses; 6% versus 42%, P = 0.01) in the subgroup of patients who received divided dose therapy. Reduced Bax immunostaining was not significant in the monthly dose group. When the two groups were combined, however, reduced Bax was significantly correlated in univariate analysis with failure to respond (21 versus 43% achieving complete response or partial response; P = 0.02), faster TTP (median, 3.7 versus 9.0 months; P = 0.02), and shorter survival (median, 10.7 versus 17.1 months; P = 0.04). Bax immunostaining was not significantly correlated with tumor histology, S-phase fraction, aneuploidy, p53 HER2, or cathepsin D, but was positively associated with Bcl-2 (P = 0.005). In multivariate analysis (Bax, tumor grade, and treatment group), reduced Bax was strongly associated with faster TTP (P approximately equal to 0.009) and shorter survival (P approximately equal to 0.001). Although highly preliminary, the finding suggest that loss of Bax immunostaining represents a novel prognostic indicator of poor response to chemotherapy and shorter survival in women with metastatic breast cancer, and raise the possibility that the subgroup of women with Bax-negative tumors may benefit from more aggressive therapy.

Adenocarcinoma↗
PubMed1995

Do DNA ploidy and S-phase fraction in primary tumour predict the response to chemotherapy in metastatic breast cancer?

The relationship between the response to chemotherapy with cyclophosphamide, epirubicin and fluorouracil as well as the time to progression of metastasised breast cancer and DNA ploidy and S-phase fraction (SPF) of primary tumours was examined using paraffin-embedded tumour tissue from 81 patients. The response to chemotherapy was significantly better in patients with tumours with a high SPF, and in addition the time to progression was longer in the high-SPF group. There was no significant difference when the DNA ploidy and response to treatment were compared.

Adult↗
PubMed1994

Major and minor breakpoint sites of chromosomal translocation t(14;18) in subtypes of non-Hodgkin's lymphomas.

The frequencies of major breakpoint region (MBR) and minor cluster region (MCR) breakpoint sites of t(14;18) were examined by polymerase chain reaction and Southern blotting in 50 non-Hodgkin's lymphomas with cytogenetic evidence of t(14;18). A translocation breakpoint was detected in 41 cases (82%). The MBR was involved in 66%, and the MCR in 16% of the cases. Most cases in the present series were lymphomas with a follicular or diffuse growth pattern, 38 being of the centroblastic/centrocytic type and eight of the centroblastic type. The series also included four lymphomas of probable non-follicular center cell origin. MBR and/or MCR breakpoints were found in all studied lymphoma subtypes and in the majority of these most of the breakpoints were in the MBR and a minor portion of the breakpoints in the MCR. Our results suggest that a breakpoint site is not related to growth pattern or neoplastic cell type in follicular center cell lymphomas with t(14;18).

Adult↗
PubMed1994

Mouse subrenal capsule assay chemosensitivity and DNA flow cytometry parameters of human melanoma metastases.

Chemosensitivity was analyzed by mouse subrenal capsule assay (SRCA) in 103 human melanoma metastases 79 of which were also analyzed by DNA flow cytometry. The most effective combination was dacarbazine, vincristine, and carmustine (DOB), followed by cisplatin plus etoposide (Plat-VP16). By the original criteria of the assay, 35% of tumors were sensitive to DOB treatment while 15% responded to Plat-VP16. Chemosensitivity of DNA diploid and aneuploid tumors showed no significant difference; 35% of the aneuploid tumors were sensitive to DOB and 19% to Plat-VP16, whereas 41% and 13% respectively of the diploid tumors were sensitive. An association between DNA index and chemosensitivity was observed. Growth of the implant was observed in 44% of tumors with a DNA index above 1.5 receiving DOB treatment, whereas only 12% of tumors with an aneuploid DNA index < or = 1.5 grew. No significant difference was observed in the SPF of chemotherapy sensitive and insensitive tumors, though a tendency to lower SPF was observed in sensitive tumors.

Adult↗
PubMed1992

Tumour growth rate and DNA flow cytometry parameters as prognostic factors in metastatic melanoma.

The prognostic value of flow cytometric parameters and tumour growth rate of melanoma metastases under the mouse renal capsule was investigated for tumours from 117 consecutive patients referred to the Helsinki University Central Hospital Melanoma Team. DNA flow cytometry (FCM) was interpretable for the tumours of 114 patients, and growth rate analysis for 82 patients, both results being available from 79 patients. Thirty-six percent of the tumours were DNA diploid and 64% DNA aneuploid. Tumour ploidy and S-phase fraction were shown by multivariate Cox model analysis to be independent prognostic variables and major determinants of survival after first recurrence. Patients with DNA diploid or aneuploid tumours survived a median 16 and 27 months, respectively. A high growth rate of tumour sample in vivo under the mouse renal capsule tended to be a sign of poor prognosis, although not reaching statistical significance. Combining the results of FCM, tumour growth rate and TNM stage, we propose a highly efficient prognostic scoring method. Patients with a score above 0.75 had a median survival of 11 months compared to 30 months among patients scoring under 0.75 (P less than 0.0001). This score was the most significant (P less than 0.0001) prognostic factor in the Cox model when TNM stage, age, ploidy, SPF, and tumour growth rate were analysed as covariates.

Adult↗