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M Virolainen

Publications and source records attributed to M Virolainen.

At least 19 recordsLinked to original sources
PubMed2001

Primary soft tissue sarcoma and its local recurrence: genetic changes studied by comparative genomic hybridization.

The aims of this study were to compare genetic aberrations in primary soft-tissue sarcomas and their local recurrences and to evaluate the genetic changes occurring during tumor progression. A primary soft-tissue sarcoma and its subsequent local recurrence were analyzed in 20 tumor pairs by comparative genomic hybridization. The samples were obtained before application of radio- or chemotherapy. Copy number aberrations were detected in 50% of the primary tumors and in 70% of the local recurrences. In primary tumors, the mean number of changes was 2.45 (range, 0 to 11) whereas in local recurrences, it was 5.05 (range, 0 to 17). The mean increase of changes from primary tumor to local recurrence was 2.6 per tumor pair (P =.02). Gains predominated over losses in both primary tumors and their local recurrences. The number of high-level amplifications was twofold in local recurrences. The most frequent gain affected 5p14-p15.1 (10% of primary tumors, 25% of local recurrences) and the most frequent loss, 9p (9p21-pter in 5% of primary tumors; 9p22-pter in 30% of local recurrences). In conclusion, our results show an increase in the number of genetic changes in local recurrences, due to tumor progression. Loss at 9p and gains at 5p and 20q were more frequent in local recurrences, and high-level amplification of 18p11.3 was not detected in any of the primary tumors. Although all these alterations were not specific to local recurrences, they may represent changes important during tumor progression.

Adult↗
PubMed2000

Soft tissue sarcomas of the lower extremity: surgical treatment and outcome.

AIMS: The aims of this retrospective follow-up study were to evaluate the justification for limb-saving multi-disciplinary treatment of soft tissue sarcomas (STS) and to report the results achieved by our treatment protocol. Local control was studied, with emphasis on tumour depth, operation margin and need for post-operative radiotherapy. METHODS: We examined 130 patients with STS in the lower limb referred to the multi-disciplinary group of Helsinki University Central Hospital. For the survival analysis 106 patients with local disease remained. The goal of treatment was to preserve a functional limb. Wide excision was attempted. If the margin was less than 2.5 cm, post-operative radiotherapy (RT) was delivered to all except 20 patients. RESULTS: Ninety-two per cent of the patients were treated by limb salvage. The success rate of free flaps was 16 out of 18. The 5-year disease-specific overall survival was 76%, metastasis-free survival 72% and local control 79%. Prognostic factors for local recurrence were extracompartmental site and large size; for development of metastases high grade, extracompartmental site and large size; for decreased disease-specific overall survival high grade, large size and advanced age. Local control of intramuscular tumours (n=6) was 100%, subcutaneous tumours (n=38) 94% and tumours penetrating the deep or muscle fascia and those locating extracompartmentally (n=62) 67%. CONCLUSIONS: Limb salvage in patients with STS is possible with an acceptable outcome by selective combination of treatment modalities. Modern plastic surgical methods with free tissue transfers are successful and often needed. Subcutaneous and intramuscular tumours have good local control. The outcome is poorest for tumours penetrating the deep or muscle fascia and for those located extracompartmentally, and patients with such tumours might be a target for adjuvant therapy. Treatment should be coordinated by multidisciplinary teams.

Adult↗
PubMed1999

Clinical correlations of genetic changes by comparative genomic hybridization in Ewing sarcoma and related tumors.

Our previous comparative genomic hybridization (CGH) study of Ewing sarcoma and related tumors showed that DNA sequence copy number increases of 1q21-q22 and of chromosomes 8 and 12 were associated with trends toward poor survival (Armengol et al., Br J Cancer 1997, 75, 1403-1409). These trends were not statistically significant. In the present study, we analyzed 28 primary Ewing sarcomas and related tumors by CGH to study whether these (or other) changes have prognostic value in these tumors. Twenty-one tumors (75%) had changes with a mean of 1.9 changes per tumor. The most frequent aberration was gain of chromosome 8 in 10 tumors (36%). Five tumors (18%) had copy number increases at 1q21-22 and 5 had gain of 7q. Copy number increase of 6p21.1-pter, gain of chromosome 12, and loss of 16q were seen in 11%. Copy number increases of 1q21-q22 and of chromosomes 8 and 12 were associated with trends toward worse outcome, but the differences did not reach statistical significance. A novel finding is the association of copy number increase at 6p with worse distant disease-free (P = 0.04) and overall survival (P = 0.004). To confirm this finding and to see whether copy number increases of 1q21-q22 and of chromosomes 8 and 12 have definite prognostic value, a larger number of cases needs to be studied.

Adolescent↗
PubMed1999

Expression of cyclin A in soft tissue sarcomas correlates with tumor aggressiveness.

Cyclins and cyclin-dependent kinases regulate the cell cycle. Cyclin A has a dual role in cell proliferation. It is essential in the S phase for DNA replication, and it is also involved in G2-M-phase transition, signifying actively dividing cells. The expression of cyclin A was determined by immunohistochemistry in paraffin sections of 126 soft tissue sarcomas. The median cyclin A score was 10.8% (range, 1-54%). Cyclin A expression correlated with the S-phase fraction, Ki-67 score, G2-M phase, and grade. It did not correlate with the size of the tumor. A high cyclin A score predicted a poor metastasis-free survival (P < 0.01) and a poor disease-specific overall survival (P = 0.01). We concluded that the expression of cyclin A is a powerful prognostic factor in soft tissue sarcoma. Moreover, the cyclin A score determines the fraction of tumor cells in the S phase and the G2 phase, which are the most sensitive cell cycle phases for current modalities of cancer treatment.

Adolescent↗
PubMed1999

Human vascular adhesion protein-1 in smooth muscle cells.

Human vascular adhesion protein-1 (VAP-1) is a dual-function molecule with adhesive and enzymatic properties. In addition to synthesis in endothelial cells, where it mediates lymphocyte binding, VAP-1 is expressed in smooth muscle cells. Here we studied the expression, biochemical structure, and function of VAP-1 in muscle cells and compared it to those in endothelial cells. VAP-1 is expressed on the plasma membrane of all types of smooth muscle cells, but it is completely absent from cardiac and skeletal muscle cells. In tumors, VAP-1 is retained on all leiomyoma cells, whereas it is lost in half of leiomyosarcoma samples. In smooth muscle VAP-1 predominantly exists as a approximately 165-kd homodimeric glycoprotein, but a trimeric (approximately 250 kd) form of VAP-1 is also found. It contains N-linked oligosaccharide side chains and abundant sialic acid decorations. In comparison, in endothelial cells dimeric VAP-1 is larger, no trimeric forms are found, and VAP-1 does not have N-glycanase-sensitive oligosaccharides. Unlike endothelial VAP-1, VAP-1 localized on smooth muscle cells does not support binding of lymphocytes. Instead, it deaminates exogenous and endogenous primary amines. In conclusion, VAP-1 in smooth muscle cells is structurally and functionally distinct from VAP-1 present on endothelial cells.

Amine Oxidase (Copper-Containing)↗
PubMed1999

Epithelioid sarcoma: an immunohistochemical analysis of 112 classical and variant cases and a discussion of the differential diagnosis.

Epithelioid sarcoma (ES) is a distinctive soft tissue neoplasm with a predilection for the distal extremities of young adults. This tumor typically contains nodular aggregates of epithelioid and spindle cells with zonal necrosis. The neoplastic cells are generally reported to coexpress keratin and vimentin and are often stated to be positive for CD34. However, there is no large series with extensive immunohistochemical data, there are few data with regard to expression of different keratin subtypes, and there are no large series discussing the epithelioid sarcoma subtypes. In the current study, we immunohistochemically evaluated 88 typical and 24 variant (8 angiomatoid, 9 large cell/rhabdoid, and 7 "fibroma-like") ESs. Nearly all ESs with typical histology (94%) were positive for keratin 8 (K8), whereas 72% were positive for K19, 48% for intermediate- and high-molecular-weight keratins (34betaEH12), and 22% for K7; reactivity with the latter two antibodies was usually seen in only a minority of tumor cells. Vimentin reactivity was present in all cases, EMA in 96% of cases and muscle-specific actin and CD34 were noted in 41% and 52% of the cases, respectively. A few ESs (7%) showed focal cytoplasmic CD31 reactivity, but none exhibited a distinctive membrane staining pattern, and examples tested for FVIIIRAg were negative. The angiomatoid, fibroma-like, and large cell-rhabdoid ES variants had immunohistochemical profiles similar to the classic cases, supporting a common pathogenesis. Although not consistently expressed in ES, the presence of CD34 is helpful in distinguishing this entity from primary and metastatic carcinomas and other sarcomas such as malignant rhabdoid tumor.

Adolescent↗
PubMed1999

Synovial sarcoma--identification of favorable and unfavorable histologic types: a Scandinavian sarcoma group study of 104 cases.

Synovial sarcoma has traditionally been regarded as a high-grade sarcoma and treated as such. Recently, specific types of poorly differentiated synovial sarcoma have been defined and shown to affect prognosis adversely. We studied 104 primary synovial sarcomas of the extremities and trunk wall without metastasis at diagnosis that were retrieved from the Scandinavian Sarcoma Group Registry (SSG) and the Swedish Cancer Registry from 1986 to 1994. Follow-up was available in all patients, median 6 (3-11) years for the survivors. There were local recurrences in 15% of patients and metastases in 33%. Histologically, the tumors were divided into favorable and unfavorable types. The favorable type had no significant cytologic atypia, and in most instances, no necrosis and a mitotic count of < 10/10 hpf. The unfavorable type included so-called poorly differentiated synovial sarcomas as well as recognizable biphasic and monophasic synovial sarcomas with prominent nuclear atypia, extreme cellularity and nuclear crowding. Designation of a tumor as having favorable vs. unfavorable histology conveyed more prognostic information than any single histologic factor. Kaplan-Meier estimates of metastasis-free survival at 5 years were 83% for patients with histologically favorable tumors and 31% for patients with histologically unfavorable tumors (95% confidence intervals 72-92% and 13-51%, respectively). These findings may influence future treatment protocols for synovial sarcoma.

Adolescent↗
PubMed1999

Comparison of genetic changes in primary sarcomas and their pulmonary metastases.

The aims of the present study were to compare genetic aberrations in primary sarcomas and their pulmonary metastases and to explore the pathways associated with disease spreading. The primary tumor and its subsequent pulmonary metastasis of 22 patients were analyzed by comparative genomic hybridization. All samples were obtained before the initiation of chemo- or radiotherapy. The mean total number of aberrations per tumor was 7.6 (range, 0-17) in primary tumors and 7. 5 (range, 0-19) in metastases. The mean numbers of high-level amplifications per tumor were similar (0.32 in primary tumors and 0. 36 in metastases). The frequencies of the most common aberrations were relatively similar in primary tumors and metastases: the most frequent gain affected 1q (minimal common regions 1q21-q23 in 36% of primary tumors and 1q21 in 45% of metastases). The most frequent losses were detected at 9p (9p22-pter in 32% of primary tumors and 9p21-pter in 32% of metastases), 10p (10p11.2-p12 in 41% of primary tumors and 10p11.2-pter in 32% of metastases), 11q (11q23-qter in 36% of primary tumors and 32% of metastases), and 13q (13q14-q21 in 45% of primary tumors and 50% of metastases). No aberrations specific to metastases were detected. An increase in the total number of changes during progression was a predominant feature in a majority of these paired samples. Also, the number of differences in the genetic profile outnumbered common changes in a majority of the samples. However, despite the heterogeneous and numerous changes, all pairs with aberrations in both specimens had some shared alterations in both samples. Genes Chromosomes Cancer 25:323-331, 1999.

Adolescent↗
PubMed1998

Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial.

BACKGROUND: Epidemiologic studies have suggested that vitamin E and beta-carotene may each influence the development of prostate cancer. In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial, we studied the effect of alpha-tocopherol (a form of vitamin E) and beta-carotene supplementation, separately or together, on prostate cancer in male smokers. METHODS: A total of 29133 male smokers aged 50-69 years from southwestern Finland were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5-8 years (median, 6.1 years). The supplementation effects were estimated by a proportional hazards model, and two-sided P values were calculated. RESULTS: We found 246 new cases of and 62 deaths from prostate cancer during the follow-up period. A 32% decrease (95% confidence interval [CI] = -47% to -12%) in the incidence of prostate cancer was observed among the subjects receiving alpha-tocopherol (n = 14564) compared with those not receiving it (n = 14569). The reduction was evident in clinical prostate cancer but not in latent cancer. Mortality from prostate cancer was 41% lower (95% CI = -65% to -1%) among men receiving alpha-tocopherol. Among subjects receiving beta-carotene (n = 14560), prostate cancer incidence was 23% higher (95% CI = -4%-59%) and mortality was 15% higher (95% CI = -30%-89%) compared with those not receiving it (n = 14573). Neither agent had any effect on the time interval between diagnosis and death. CONCLUSIONS: Long-term supplementation with alpha-tocopherol substantially reduced prostate cancer incidence and mortality in male smokers. Other controlled trials are required to confirm the findings.

Anticarcinogenic Agents↗
PubMed1998

Chromosome band 1q21 is recurrently gained in desmoid tumors.

DNA sequence copy number changes were studied by comparative genomic hybridization (CGH) in 28 desmoid tumors. Changes were detected in 12 tumors (43%) with a mean of 1.4 changes per sample (range: 1 to 7). Out of 12 tumors associated with pregnancy or Gardner's syndrome, only two displayed changes. The minimal common regions of the most frequent gains were 1q21 (39%), chromosome 20 (32%), and 9p12 (21%). No high-level amplifications were detected. Losses of DNA sequences were two times less frequent than gains and the minimal common regions of the most frequent losses were 6q16-q21 (14%), 5q14 (11%), and 13q21-q31 (11%).

Adolescent↗
PubMed1998

Genetic imbalances in 67 synovial sarcomas evaluated by comparative genomic hybridization.

We used comparative genomic hybridization (CGH) to evaluate DNA sequence copy number changes in 67 synovial sarcomas of both monophasic and biphasic histological subtypes. Changes (mean among aberrant cases: 4.7 aberrations/tumor; range: 1-17), affecting most often entire chromosomes or chromosome arms, were detected in 37 sarcomas (55%). Gains and losses were distributed equally, but different chromosomes were affected with variable frequencies. The most frequent aberrations, each detected in 9-11 of 67 tumors, were gain of 8q and gain at 12q (12q14-15 and 12q23-qter), loss of 13q21-31, and loss of 3p. Other frequent changes (in 7 or 8 cases) included gains at 2p, 1q24-31, and 17q22-qter, and losses at 3cen-q23 and 10q21. High-level amplifications were seen in 7 cases. A total of 16 regions were detected. Two of them, 8p12-qter and 21q21-qter, seen in 4 and 2 tumors, respectively, were recurrent. No aberrations specific to histological subtype were identified. However, genetic changes in the monophasic tumors were more complex and numerous (mean among aberrant cases: 5.3 aberrations/tumor; range: 1-17) than in the biphasic tumors (mean: 2.5 aberrations/tumor; range: 1-5), and high-level amplifications occurred more frequently. All but 1 of the sarcomas showing high-level amplification were of the monophasic subtype. These findings may reflect differences in the pathogenesis and biological behavior of both histological subtypes of synovial sarcoma.

Adolescent↗
PubMed1997

Overrepresentation of 1q21-23 and 12q13-21 in lipoma-like liposarcomas but not in benign lipomas: a comparative genomic hybridization study.

Twenty lipomatous tumors, including eight lipoma-like liposarcomas and 12 benign lipomas, were analyzed using comparative genomic hybridization (CGH). DNA sequence copy number changes detected in five lipoma-like liposarcomas (mean, 1.1 aberrations/tumor; range, 0-2) consisted of gains of 12q13-21 (five tumors) and 1q21-23 (four tumors). Two of the tumors showed high-level amplification at 12q14-21 and one tumor at 1q21-22. No copy number changes were found in lipomas. Overrepresentation of 1q and 12q sequences was a recurrent finding in lipoma-like liposarcomas but not in lipomas. Thus, CGH may help in the differential diagnosis of low-grade or borderline adipose neoplasms.

Adult↗
PubMed1997

Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to detect copy number changes of DNA sequences in the Ewing family of tumours (ET). We analysed 20 samples from 17 patients. Fifteen tumours (75%) showed copy number changes. Gains of DNA sequences were much more frequent than losses, the majority of the gains affecting whole chromosomes or whole chromosome arms. Recurrent findings included copy number increases for chromosomes 8 (seven out of 20 samples; 35%), 1q (five samples; 25%) and 12 (five samples; 25%). The minimal common regions of these gains were the whole chromosomes 8 and 12, and 1q21-22. High-level amplifications affected 8q13-24, 1q and 1q21-22, each once. Southern blot analysis of the specimen with high-level amplification at 1q21-22 showed an amplification of FLG and SPRR3, both mapped to this region. All cases with a gain of chromosome 12 simultaneously showed a gain of chromosome 8. Comparison of CGH findings with cytogenetic analysis of the same tumours and previous cytogenetic reports of ET showed, in general, concordant results. In conclusion, our findings confirm that secondary changes, which may have prognostic significance in ET, are trisomy 8, trisomy 12 and a gain of DNA sequences in 1q.

Adolescent↗
PubMed1997

Comparative genomic hybridization of malignant fibrous histiocytoma reveals a novel prognostic marker.

DNA sequence copy number changes were studied by comparative genomic hybridization (CGH) along all chromosomes in 58 samples of malignant fibrous histiocytoma (MFH). The material consisted of 43 primary tumors (9 of myxoid and 34 of storiform-pleomorphic subtype), 13 local recurrences (2 myxoid and 11 storiform-pleomorphic), and 2 metastases (1 myxoid and 1 storiform-pleomorphic). Genetic aberrations, with a mean of 5.5 changes per sample (range, 0 to 22), were detected in 47 of 58 samples (81%). The minimal common regions of the most frequent gains were 1p31 (33%), 9q31 (29%), 5p14-pter (26%), 7q32 (24%), and 7p15-pter (22%). High-level amplifications were detected in 16 of the 58 samples (28%). High-level amplification of 13q31-qter was seen in four tumors (7%); other high-level amplifications were more sporadic. Losses of DNA sequences were less frequent than gains. The minimal common regions of the most common losses were 13q21 (21%) and 13q22 (21%). Statistically significant correlation was found between gain of 7q32 and the rates of worse metastasis-free survival (P = 0.01) and overall survival (P = 0.004). The gain of 7q32 retained its prognostic significance also in a multivariate analysis with tumor size and grade. Gain of 1p31 was associated with a trend to decreased overall survival. Gains of 5p14-pter and 9q31 and losses of 13q21 and/or 13q22 did not have any prognostic value; neither did the total number of aberrations, total number of gains, or total number of losses per sample.

Adult↗
PubMed1996

Gains and losses of DNA sequences in liposarcomas evaluated by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to detect and map the regions of gain, high-level amplification, and loss of DNA sequences in 14 liposarcomas. Thirteen tumors showed DNA sequence copy number changes of one or more genomic regions (mean, six aberrations/tumor; range, 0-17). These aberrations were observed in almost every chromosome but some chromosomal regions were affected more often than others. DNA sequence gains were more frequent than losses. The most common gain was seen at 12q14-21 (50% of tumors). Other frequent gains (29%) were of 1q21-24, 8cen-q21.2, 19q, and 20q. High-level amplification was observed in six (43%) tumors and included as minimal common segments bands 12q15, 1q22, and 1q24. In five (36%) tumors, sequences at 1q21-24 and 1q32 were found to be gained simultaneously with 12q14-21, which means that in 71% of the tumors with gain at 12q, an increase of DNA sequence copy number at 1q was also observed. The most common losses of DNA sequences (21%) occurred from regions 9p21-pter and 13q21-qter. Most of the aforementioned regions have not previously been reported to be altered in liposarcomas. The detection of a novel recurring amplicon at 1q21-24 with high-level amplification at 1q22 and frequent simultaneous DNA sequence gain at 12q14-21 (high-level amplification at 12q15) suggests that genes linked to both these regions may play a significant role in the development and progression of liposarcomas.

Adult↗
PubMed1996

Cytogenetic study of extraskeletal mesenchymal chondrosarcoma. A case report.

Extraskeletal mesenchymal chondrosarcoma (EMC) is a rare and highly malignant type of chondrosarcoma of soft tissue origin. We performed a cytogenetic study on a patient with EMC. Cytogenetic analysis revealed the tumor karyotype: 48-49,XX, t(4;9)(q23;q22), add(10)(q?26), +16, ?del(19)(p13), +1-2mar[cp12] / 48-50,idem, t(1;20)(q21;q13), +mar[cp6] / 46,XX [7].

Adult↗
PubMed1996

The importance of a multidisciplinary group in the treatment of soft tissue sarcomas.

In 1987, a multidisciplinary soft tissue sarcoma (STS) group was established and a treatment protocol was set up. By 1993, there were 193 patients with a diagnosis of STS of the superficial trunk or extremities. 134 patients were referred with primary (stage M0) tumours and treated with curative or palliative intention. Nine amputations were performed. 94 (70%) patients were treated with wide or compartment surgery (n = 62) or marginal surgery combined with postoperative radiotherapy (n = 32). According to the protocol, these patients had received adequate treatment. 18 patients have recurred locally (13%) (median follow-up: 36 months). 12 were salvaged. 33 had metastases. The estimated 3-year survival, local control and disease-free survival rates are 79, 87 and 69%, respectively. These results compare favourably with previously published results from this hospital and from a nationwide study. The improved results emphasise the importance of a multidisciplinary STS group.

Adolescent↗