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DNA content evaluation for epithelial ovarian cancer identification

100%

Tomé A., Leal I., Palmeiras C., Matos E., Amado J., Abreu M., Lopes C.

Current Gynecologic Oncology

2018

vol. 16

issue 1

3-10

Objective: To assess the cellular DNA status of epithelial ovarian cancer cells for clinical stage identification and its effect on survival. Methods: Sixty-two patients treated by primary surgery and six courses of platinum-based chemotherapy were enrolled. The surgical stage was analyzed in correlation with DNA ploidy, S-phase fraction and DNA index. DNA analysis was performed via image cytometry. Results: From the 62 cases, 38 were International Federation of Gynecology and Obstetrics (Fédération Internationale de Gynécologie et d’Obstétrique, FIGO) stage I and II, 24 – stage III and IV. In the DNA histograms obtained, the DNA index ranged from 0.85 to 3.02. Sixteen were classified as diploid and 46 as aneuploid (18 multiploid). S-phase fraction ranged from 9.8 to 51%. The aneuploid cells with DNA content above 5C ranged from 0.0 to 77.2%. Patients diagnosed with FIGO III and IV (vs. I and II) were 3.3 times more likely to die. Only in FIGO stage I and II the survival differed significantly for the different groups of ploidy. The risk of death for the multiploid (vs. diploid) group is 6.4 times and for aneuploid (vs. diploid) 2.3 times. Overall survival was better in the group with low DNA index. The low percentage compared with a high percentage of 5C cells ploidy groups showed association with mortality. The death hazard for the S-phase >33 median group is 4.9 times the hazard in relation to the S-phase <33. Conclusions: DNA ploidy, DNA index, S-phase, and 5C cells are important prognosticators for epithelial ovarian cancer mainly in early stages.

Cel: Ocena statusu DNA komórek nabłonkowego raka jajnika w różnych stopniach zaawansowania klinicznego i jego wpływ na przeżycie. Metoda: Do badania zakwalifikowano 62 pacjentki leczone operacyjnie i za pomocą chemioterapii opartej na platynie (6 kursów). Stopień zaawansowania klinicznego nowotworu analizowano w odniesieniu do ploidalności DNA, frakcji fazy S oraz indeksu DNA. Analizę DNA przeprowadzono z zastosowaniem cytometrii obrazowej. Wyniki: Spośród 62 pacjentek 38 zakwalifikowano jako stopień zaawansowania I i II, natomiast 24 – jako stopień III i IV wg FIGO (International Federation of Gynecology and Obstetrics). W otrzymanych histogramach DNA indeks DNA wynosił 0,85–3,02. Szesnaście przypadków raka zaklasyfikowano jako diploidalne, natomiast 46 – jako aneuploidalne (18 multiploidalnych). Frakcja fazy S mieściła się w przedziale 9,8–51%. Odsetek komórek aneuploidalnych z zawartością DNA powyżej poziomu 5C wynosił 0,0–77,2%. Ryzyko śmierci było 3,3-krotnie większe w przypadku pacjentek z chorobą w stopniu zaawansowania FIGO III i IV (w porównaniu z I i II). Jedynie w przypadku stopni zaawansowania FIGO I i II odnotowano istotnie różnice w przeżywalności między poszczególnymi grupami ploidalności. Ryzyko śmierci było 6,4-krotnie większe w przypadku multiploidalności i 2,3-krotnie większe w przypadku aneuploidalności (w porównaniu z diploidalnością). Dłuższe przeżycie ogólne odnotowano w grupie o niskim indeksie DNA. Wykazano związek między niskim odsetkiem komórek 5C, w porównaniu z wysokim odsetkiem tych komórek w grupach poliploidalnych, a śmiertelnością. Ryzyko śmierci było 4,9-krotnie większe w grupie z medianą liczby komórek w fazie S >33 w porównaniu z medianą liczby komórek w fazie S <33. Wnioski: Ploidalność DNA, indeks DNA, faza S oraz obecność komórek 5C to ważne czynniki prognostyczne u pacjentek z nabłonkowym rakiem jajnika, głównie we wczesnym stadium.

Comparative studies of nuclear DNA content in benign and malignant thyroid lesions.

75%

Konarska L., Skierski J., Ellert A., Steinbrich J., Woźniak A., Kałczak M.

Acta Biochimica Polonica

2001

vol. 48

issue 3

783-793

Currently available data suggest that DNA aneuploidy is associated with aggressive behavior of and unfavorable prognosis in several malignant human tumors as compared with diploid malignancies. However, the diagnostic and prognostic importance of flow cytometric DNA measurements in the case of thyroid neoplasms remains controversial. Therefore, the aim of our study was to evaluate utility of DNA index (DI) and proliferative index (PI) in distinguishing benign from malignant thyroid lesions taking into account the possible influence of intra-tumor heterogeneity and tissue preparation mode on DNA flow-cytometry measurements. A retrospective study was performed on 71 paraffin-embedded specimens from 57 patients with benign and malignant thyroid pathologies: 13 colloid goitres, 12 parenchymatous goitres, 19 adenomas and 13 carcinomas. In 14 of 57 cases two separate specimens taken from different areas of the same lesion were analysed and DNA parameters were compared. Additionally, flow cytometry DNA analysis was parallelly performed on 3 adjacent but differently processed tissue sections (fresh, formalin-fixed and paraffin-embedded) taken from each of 26 surgically excised thyroid lesions. DNA content was also analysed in both fresh and formalin-fixed twin specimens of normal pig thyroid glands (N = 6). We demonstrated that all tumors diagnosed as thyroid carcinomas were associated with abnormal nuclear DNA content although aneuploidy was not found specific to malignant thyroid tumors. Aneuploid samples of benign thyroid lesions exhibited higher proliferative activity, expressed as mean PI values, than diploid ones. In carcinomas the mean PI values were significantly higher than in benign lesions, independently whether they concerned aneuploid or diploid tissues. Considering intra-tumor heterogeneity, the flow cytometric DNA parameters can be assumed as reproducible despite differences in the mode of tissue fixation and preparation for analysis.

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1 Acta Biochimica Polonica

1 Current Gynecologic Oncology

1 2018

1 2001

1 Abreu M.

1 Amado J.

1 Ellert A.

1 Kałczak M.

1 Konarska L.

1 Leal I.

1 Lopes C.

1 Matos E.

1 Palmeiras C.

1 Skierski J.

1 Steinbrich J.

1 Tomé A.

1 Woźniak A.

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DNA content evaluation for epithelial ovarian cancer identification

Comparative studies of nuclear DNA content in benign and malignant thyroid lesions.