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Now showing items 1 - 16 of 42

  • P04.78 Ultrarapid FGFR3 immunostaining for diagnosis of gliomas harboring FGFR3 gene fusions

    Mäntylä, S   Haapasalo, J   Ilvesaro, J   Nordfors, K   Isola, J   Haapasalo, H   Nykter, M   Granberg, K  

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  • p53 expression and cell proliferation as prognostic factors in laryngeal squamous cell carcinoma.

    Hirvikoski, P   Kumpulainen, E   Virtaniemi, J   Johansson, R   Haapasalo, H   Marin, S   Halonen, P   Helin, H   Raitiola, H   Pukander, J   Kellokumpu-Lehtinen, P   Kosma, V M  

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  • Consistency of Quantitative Methods in Ovarian Tumor Histopathology

    Haapasalo, H   Collan, Y   Montironi, R   Pesonen, E   Atkin, N B  

    Two mitotic activity indices, volume fraction of neoplastic epithelium, nuclear area, nuclear perimeter, and shortest nuclear axis were estimated in 46 ovarian tumors by three observers in two independent laboratories. The mitotic activity index, the volume corrected mitotic index (M/V index) and subjective volume fraction estimates showed a very good correlation from the same fields by two observers in the same laboratory (r = .999, .995, .950). Repeat estimates from different fields by the same observer showed coefficient values of .949, .939, and .813, and estimates by two different observers within one laboratory values of .949, .936, and .789, respectively. The correlation between two independent observers in different laboratories was also good (r = .894, .834, .834, respectively). Grading based on morphometric measurements was uniformly performed in 90-100% of cases in an interfield interobserver intralaboratory situation, and in 79-97% (M/V index) or 76-93% (mitotic activity index) in an interlaboratory situation. Because the cases near the grade limits were more often differently graded than other cases, the methods allowed the pathologist to locate the probably incorrectly graded cases. Morphometry of ovarian tumors was shown to be easy, which makes morphometric malignancy grading systems, potentially able to support diagnostic and therapeutic decisions in practice.
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  • c-erbB-2 in astrocytomas: infrequent overexpression by immunohistochemistry and absence of gene amplification by fluorescence in situ hybridization

    Haapasalo, H   Hyytinen, E   Sallinen, P   Helin, H   Kallioniemi, OP   Isola, J  

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  • Mitosis counting in tumors.

    Haapasalo, H   Collan, Y  

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  • Amplification of the epidermal growth factor receptor in astrocytic tumours by chromogenic in situ hybridization: association with clinicopathological features and patient survival.

    Jarvela, Sally   Jarvella, S   Helin, H   Haapasalo, J   Jarvela, Timo   Jarvella, T   Junttila, T T   Elenius, K   Tanner, M   Haapasalo, H   Isola, J  

    Chromogenic in situ hybridization (CISH) was used to detect amplification of the epidermal growth factor receptor (EGFR) gene in tissue microarrays of tumours derived from 287 patients with grade II-IV diffuse astrocytomas. Amplification was found in 32% of the tumours with a highly significant association with histological grade (4% in grade II, 21% in grade III and 39% in grade IV; P < 0.001). Amplification of the EGFR gene was more common in primary than in secondary glioblastomas (41%vs. 16%, P = 0.033). Overexpression of EGFR mRNA and protein (wild-type and vIII variant) was found to correlate with EGFR gene amplification (P = 0.028, P = 0.035 and P = 0.014 respectively), but wild-type EGFR protein was also frequently overexpressed in tumours without EGFR gene amplification. Patients with older age (P < 0.001) and tumours with lack of p53 overexpression (P = 0.03) and higher apoptosis rate (P < 0.001) had significantly more EGFR gene amplifications than their counterparts. No such correlation with apoptosis was found in glioblastomas. The survival of patients with EGFR gene-amplified grade III tumours was significantly shorter than in those with grade III non-amplified tumours (P = 0.03). No such difference was noted in glioblastomas (grade IV tumours). Our data verify the central role of EGFR in the pathobiology of astrocytic tumours, and highlight the advantages of CISH as a simple and practical assay to screen for EGFR gene amplification in astrocytic tumours.
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  • High topoisomerase II alpha expression associates with high proliferation rate and and poor prognosis in oligodendrogliomas

    Miettinen, HE   Jarvinen, TAH   Kellner, U   Kauraniemi, P   Parwaresch, R   Rantala, I   Kalimo, H   Paljarvi, L   Isola, J   Haapasalo, H  

    The role of molecular markers predicting the prognosis and the selection of patients for further adjuvant therapies is not well established in oligodendroglioma patients. A potential prognostic as well as a therapeutically predictive factor, topoisomerase II alpha (topoII alpha), is a molecular target for certain cytotoxic drugs. Its expression has been shown to correlate with the prognosis in a number of different cancers and with the chemosensitivity of cancer cells in vitro. The expression of topoII alpha was evaluated immunohistochemically in 59 oligodendrogliomas and in 29 mixed gliomas with a predominating oligodendroglioma component by the use of a tissue microarray technique. In the gliomas, the percentage of topoII alpha immunopositive cells protein expression varied from 0.0 to 49.1% (5.2 +/- 8.3%, mean +/- SD). In oligoastrocytomas, the mean topoII alpha score was significantly higher in the oligodendroglioma than in the astrocytoma component of the tumour (5.37 +/- 5.58% vs. 1.89 +/- 2.49%, P = 0.018). A significant association was found between the high proportion of topoII alpha positive cells and high grade of the tumour (P < 0.0001), high tumour proliferation rate (P < 0.0001), p53 overexpression (P = 0.01) and high expression of tumour suppressing retinoblastoma protein (P = 0.023). TopoII alpha expression was not associated with the age or sex of patient, and the rate of apoptosis. TopoII alpha expression associated highly significantly with patient prognosis; a significantly higher proportion of patients with low rather than with high topoII alpha score was alive at the end of the 5-year follow-up (P = 0.03). Cox analysis was used to demonstrate that topoII alpha had an independent prognostic value for survival (P = 0.034). In conclusion, high topoII alpha expression characterizes oligodendrogliomas and oligoastrocytomas which are poorly differentiated, have high proliferation rate, and has prognostic value for overall survival of these patients. Therefore, topoII alpha may be a useful marker for better targeted selection of poor prognosis oligodendroglioma patients for adjuvant therapy.
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  • Antioxidant enzymes in oligodendroglial brain tumors: association with proliferation, apoptotic activity and survival (vol 77, pg 141, 2006)

    Jarvela, S   Bragge, H   Paunu, N   Jarvela, T   Paljarvi, L   Kalimo, H   Helen, P   Kinnula, V   Soini, Y   Haapasalo, H  

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  • Chromogenic in situ hybridization-detected hotspot MYCN amplification associates with Ki-67 expression and inversely with nestin expression in neuroblastomas

    Korja, M   Finne, J   Salmi, TT   Kalimo, H   Karikoski, R   Tanner, M   Isola, J   Haapasalo, H  

    Since neuroblastomas are intratumorally heterogeneous, the analysis of genetic and biologic features of randomly selected tumor specimen spots may lead to erroneous conclusions. Our purpose was therefore to construct an easily assessable and strictly defined strategy to unify the detection of various molecular markers in paraffin-embedded neuroblastoma samples. We selected tumor specimen spots of highest proliferation activity, that is, hotspots, for the analysis of MYCN amplification status and proliferation-associated molecular markers, such as nestin, which role in neuroblastoma specimens was evaluated for the first time. Using a chromogenic in situ hybridization (CISH) technique, we showed that patients with a MYCN copy number higher than six in anti-Ki-67-detected hotspots have significantly worse overall survival prognosis than patients with low MYCN copy numbers (P = 0.0006). The chosen cutoff value of six was shown to dichotomize MYCN-amplified neuroblastomas at least as specifically as Southern blot hybridization, in which amplification was defined by a copy number of >= 10. Interestingly, we also detected without difficulty MYCN-amplified neuroblastic cells in bone marrow samples using the CISH technique. The proliferation activity, assessed with an anti-Ki-67-based proliferation index, was significantly higher in MYCN-amplified than in nonamplified hotspots. The proliferation indices of the hotspots had also a significant correlation with the prognosis ( International Classification) and histological type, whereas the proliferation accelerator Id2 did not associate with any of the mentioned parameters. The expression of nestin associated inversely with MYCN amplification (P = 0.018), which challenges a previously suggested role of nestin in neuroblastomas. In summary, hotspot focusing provides a means of analyzing proliferation-associated markers in neuroblastomas, and together with the CISH detection of the MYCN copy number enables an easy and reliable examination of MYCN status in neuroblastomas.
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  • Chromosome imbalances in familial gliomas detected by comparative genomic hybridization.

    Paunu, N   Sallinen, S L   Karhu, R   Miettinen, H   Sallinen, P   Kononen, J   Laippala, P   Simola, K O   Helen, P   Haapasalo, H  

    Familial occurrence of gliomas, in the absence of well-defined hereditary multisystem disorders, is reported occasionally. We describe 17 families that have been afflicted with two or more gliomas but do not raise suspicion of other inheritable syndromes. The families were identified among 369 consecutive glioma patients operated at the Tampere University Hospital during 1983-1994. We applied comparative genomic hybridization (CGH) analysis on 21 gliomas occurring in these 17 families. The most frequent genetic alterations, detected in over 20% of the tumors, were losses of 6q, 10, 4q, 9p and gains of 7, 19, 20q, 1p. We compared the chromosomal alterations detected in the familial gliomas to those reported previously on 209 sporadic gliomas in nine different CGH studies. In this comparison, the familial gliomas more often showed losses of chromosome arms 4q and 6q and gains of 1p and 22q. The most frequent losses (9/21 tumors) in the familial gliomas resided on chromosome arm 6q (P = 0.005, Fisher's exact test; with Bonferroni correction, P = 0.04). The loss of 6q was also the most common intrafamilial aberration, present in four separate gliomas belonging to two families. The minimal common area of loss on this chromosome resided at 6q14-16. In conclusion, we have found several characteristic aberrations by CGH in the familial gliomas and we present new chromosomal regions possibly involved in the familial predisposition to gliomas. Copyright 2000 Wiley-Liss, Inc.
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  • Arm-specific multicolor fluorescence in situ hybridization reveals widespread chromosomal instability in glioma cell lines

    Sallinen, SL   Sallinen, P   Ahlstedt-Soini, M   Haapasalo, H   Helin, H   Isola, J   Karhu, R  

    An investigation of numerical and structural chromosome aberrations using chromosome arm-specific multicolor fluorescence in situ hybridization (armFISH) revealed considerable genetic heterogeneity among and within 11 glioma cell lines. Despite the substantial variation in numerical chromosome alterations among the cell lines, several distinct and glioma growth-associated losses or gains were frequently observed, that is, losses of chromosomes 10, 13, and 22 and gain of chromosome 7 in particular. Structural aberrations frequently affected chromosomes 1, 4, 7, 16, and 19; however, no single structural chromosome aberration common to all or even several glioma cell lines could be found. Structural alterations were often multiform, and a large variety of unstable chromosome structures were detected. Two of the cell lines also harbored small marker chromosomes containing mainly heterochromatin and chromosomal insertions within heterochromatic regions. Altogether, the armFISH provides a versatile tool for the identification of chromosomal aberrations as well as their formation patterns in tumors with a complex genome at the level of chromosome arms. (C) 2003 Elsevier Inc. All rights reserved.
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  • Absence of KLF6 gene mutations in human astrocytic tumors and cell lines

    Koivisto, PA   Zhang, XH   Sallinen, SL   Sallinen, P   Helin, HJ   Dong, JT   Van Meir, EG   Haapasalo, H   Hyytinen, ER  

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  • Cancer incidence in families with multiple glioma patients

    Paunu, N   Pukkala, E   Laippala, P   Sankila, R   Isola, J   Miettinen, H   Simola, KOJ   Helen, P   Helin, H   Haapasalo, H  

    Twenty-four Finnish families with 2 or more glioma patients were identified through questionnaires sent to 369 consecutive glioma patients receiving surgery at Tampere University Hospital during 1983-94. To explore whether unusual cancer susceptibility is involved, the cancer risk of 2,664 family members was estimated using population-based data from the Finnish Cancer Registry. Among the total cohort of relatives, 88 cancers were observed during 1953-97. The overall cancer risk among 12 families with juvenile onset gliomas was significantly decreased (standardized incidence ratio [SIR] 0.6, 95% confidence interval [Cl]: 0.4-0.9). Among 12 families with adult onset gliomas, the overall cancer risk was equal to that of the reference population (SIR 1.1, 95% Cl: 0.8-1.4) whereas the risk of skin melanoma (SIR 4.0, 95% CI: 1.5-8.8) and meningioma (SIR 5.5, 95% Cl: 1.1-16) were significantly increased. Several other tumors including those associated with neurofibromatosis 1 and 2, tuberous sclerosis and Li-Fraumeni and Turcot syndromes were surveyed, but no elevated risks were observed. In conclusion, the presence of meningiomas and skin melanomas in glioma families may indicate a novel association as a cancer susceptibility trait. (C) 2002 Wiley-Liss, Inc.
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  • Humeral dimensions after long term unilateral loading

    Haapasalo, H   Siev?nen, H   Kannus, P   Oja, P   Vuori, I  

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    A retrospective histological analysis has been carried out on 537 cases of transitional-cell bladder carcinoma, followed-up over a period of 9 years. In the first part of the study WHO grade 2 tumours were analysed and a number of independent factors predictive for survival identified. In a multivariate analysis the T category and M/V index (number of mitotic figures/mm2 neoplastic epithelium) were the most important prognostic factors. In a subsequent analysis of the whole series of 537 cases, overall the M/V index was not as important in predicting survival as the stage of the tumour. However, in superficial tumours (Ta-T1) subsequent analysis showed that the M/V index alone could be used to predict survival.
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  • Managing creativity: is it possible to control the birth of innovation in product design?

    Haapasalo, H   Kess, P  

    The intention of this article is to explain how to improve design and product development. The objective is to point out different functions or mechanisms of the core of design tasks. Furthermore the aim is to analyse systematic control procedures in creative work. This review consists of extensively processed theoretical material connected to experiences in practical design. The beginning of the article is a fundamental antithesis between creative and systematic approaches and also a theoretical basis for the purpose of design. Later on it is determined, from an engineering point of view, how innovations are produced or how creative ideas pop into the conscious mind. The analysis is based on the empirical and literary material obtained in the research project carried out in the years 1995-1999.
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