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  • 1.
    Blom, René
    et al.
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Guerrieri, C.
    Department of Pathology, St. Vincent's Hospital, New York, New York, USA.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Malmström, Helena
    Linköping University, Department of Molecular and Clinical Medicine.
    Simonsen, E.
    Leiomyosarcoma of the uterus: A clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 49 cases1998In: Gynecologic Oncology, ISSN 0090-8258, Vol. 68, no 1, p. 54-61Article in journal (Refereed)
    Abstract [en]

    AIM: The authors analyzed in a retrospective manner the prognostic significance of p53 and mdm-2 expression, DNA ploidy, S-phase fraction (SPF), and traditional clinical and pathological prognostic factors in patients with uterine leiomyosarcomas. MATERIAL: Forty-nine patients were diagnosed with uterine leiomyosarcoma (25 stage I, 4 stage II, 8 stage III, and 12 stage IV). DNA flow cytometric analysis and immunohistochemical staining for p53 and mdm-2 were performed on paraffin-embedded archival tissue from the uterine tumors. RESULTS: Of the 49 patients, 35 (71%) died of disease and 2 died of intercurrent disease. The 5-year survival rate was 33%. FIGO surgical stage, DNA ploidy, SPF, mitotic index, cellular atypia, and tumor grade obtained significance (P < 0.05) in a univariate survival analysis of the leiomyosarcomas. In a multivariate analysis with survival as the end point, stage was found to be the most important factor (P = 0.007); DNA ploidy (P = 0. 045) and SPF (P = 0.041) also had independent prognostic significance. For FIGO stage I tumors, DNA ploidy (P = 0.04) and tumor grade (P = 0.01) were statistically significant in a univariate analysis, while only grade had independent prognostic significance (P = 0.01) in a multivariate analysis. In a univariate analysis including only FIGO stage I and II tumors with disease-free survival as the end point, p53 overexpression (P = 0.0016), DNA ploidy (P = 0.042), and tumor grade (P = 0.008) obtained significance. In a multivariate analysis, only p53 had independent statistical significance (P = 0.01). All p53 immunopositive stage I-II tumors recurred within 28 months from diagnosis. CONCLUSION: This study found that stage represents the most important prognostic factor for uterine leiomyosarcomas. DNA ploidy and SPF had independent prognostic value. DNA flow cytometry is useful in gaining additional prognostic information. In stage I patients, tumor grade gives significant information regarding clinical outcome. In addition, p53 overexpression may predict a higher risk of recurrence in early stage leiomyosarcomas.

  • 2.
    Blom, René
    et al.
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Guerrieri, C.
    Department of Pathology, St. Vincent's Hospital, New York, New York, USA.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Malmström, Helena
    Linköping University, Department of Molecular and Clinical Medicine.
    Sullivan, S.
    Simonsen, E.
    Malignant mixed Mullerian tumors of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 44 cases1998In: Gynecologic Oncology, ISSN 0090-8258, Vol. 68, no 1, p. 18-24Article in journal (Refereed)
    Abstract [en]

    AIM: The authors retrospectively analyzed the prognostic significance of p53, mdm-2, DNA ploidy, S-phase fraction (SPF), and traditional clinical and pathologic factors in patients with malignant mixed Müllerian tumors (MMMT) of the uterus. METHODS: Between 1970 and 1995, 44 uterine tumors were diagnosed as MMMT (21 stage I, 2 stage II, 10 stage III, and 11 stage IV). Thirty-two were homologous type and 12 were heterologous type. DNA flow cytometry and immunohistochemical analysis for p53 and mdm-2 overexpression were performed on paraffin-embedded archival tissue. RESULTS: 68% of the tumors were nondiploid and 61% had an SPF greater than 10%. Sixty-one percent overexpressed p53 and 25% were mdm-2-positive. Furthermore, 91% of the tumors had a mitotic count greater than 10/10 hpf and 95% had high-grade cytologic atypia. Twenty-seven (61%) patients died of tumor and 6 (14%) died of intercurrent disease. Eleven (25%) patients are alive with no evidence of disease. The median follow-up for patients still alive was 59 months (range, 28-178 months). The overall 5-year survival rate was 38%. In a univariate analysis that included stage, histologic type, DNA ploidy, SPF, p53, mdm-2, mitotic index, and age, and with survival as the end point, only stage reached statistically prognostic significance. CONCLUSION: The majority of the tumors had obvious signs of aggressiveness such as high grade, high mitotic count, nondiploid pattern, high SPF, and overexpression of p53. This study found that stage is the most important prognostic factor for survival in MMMTs of the uterus.

  • 3.
    Malmström, Helena
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine.
    Svensson, Emma M.
    Gilbert, M. Thomas P.
    Willerslev, Eske
    Gotherstrom, Anders
    Holmlund, Gunilla
    More on contamination: The use of asymmetric molecular behavior to identify authentic ancient human DNA2007In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 24, no 4, p. 998-1004Article in journal (Refereed)
    Abstract [en]

    Authentication of ancient human DNA results is an exceedingly difficult challenge due to the presence of modern contaminant DNA sequences. Nevertheless, the field of ancient human genetics generates huge scientific and public interest, and thus researchers are rarely discouraged by problems concerning the authenticity of such data. Although several methods have been developed to the purpose of authenticating ancient DNA (aDNA) results, while they are useful in faunal research, most of the methods have proven complicated to apply to ancient human DNA. Here, we investigate in detail the reliability of one of the proposed criteria, that of appropriate molecular behavior. Using real-time polymerase chain reaction (PCR) and pyrosequencing, we have quantified the relative levels of authentic aDNA and contaminant human DNA sequences recovered from archaeological dog and cattle remains. In doing so, we also produce data that describes the efficiency of bleach incubation of bone powder and its relative detrimental effects on contaminant and authentic ancient DNA. We note that bleach treatment is significantly more detrimental to contaminant than to authentic aDNA in the bleached bone powder. Furthermore, we find that there is a substantial increase in the relative proportions of authentic DNA to contaminant DNA as the PCR target fragment size is decreased. We therefore conclude that the degradation pattern in aDNA provides a quantifiable difference between authentic aDNA and modern contamination. This asymmetrical behavior of authentic and contaminant DNA can be used to identify authentic haplotypes in human aDNA studies.

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