Combined flow cytometry determination of S-phase fraction and DNA ploidy is an independent prognostic factor in node-negative invasive breast carcinoma: analysis of a series of 271 patients with stage I and II breast cancer

Moureau-Zabotto, L.; Bouchet, C.; Cesari, D.; Uzan, S.; Lefranc, J.-P.; Antoine, Martine; Genestie, Catherine; Deniaud-Alexandre, É.; Bernaudin, J.-F.; Touboul, E.; Fleury‐Feith, Jocelyne

doi:10.1007/s10549-004-7047-1

Cited by 27 publications

(21 citation statements)

References 34 publications

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“…The advantage of the present study is the relatively large subject group and the extensive period of observation. The existing literature contains only a few reports on ploidy-related 10-year survival rates, the authors of which confirm the prognostic significance of abnormal DNA content in endometrial carcinoma [35], breast carcinoma [36], or urinary bladder carcinoma patients [37]. In 2003 Gawrychowski et al presented the analysis of a decade-long observation of 191 NSCLC patients, in which they stressed the significance of the percentage of S-phase cells as an independent prognostic factor.…”

Section: Discussionmentioning

confidence: 99%

TORAKOCHIRURGIA DNA ploidy as an independent prognostic factor: 10-year results in a group of patients surgically treated for squamous cell lung cancer

Kasprzyk¹,

Dyszkiewicz²,

Roszak³

et al. 2012

kitp

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StreszczenieWstęp: Duża zmienność biologiczna raka płuca powoduje, że mimo określonego typu histologicznego i stopnia zaawansowania raka wg klasyfikacji TNM przebieg choroby jest trudny do przewidzenia. Dlatego poszukuje się molekularnych i biochemicznych czynników mających znaczenie prognostyczne i pomocnych w kwalifikacji chorych do pooperacyjnej chemioterapii. Jednym z takich czynników mogą być zaburzenia zawartości DNA w komórkach nowotworowych, choć opinie na temat rokowniczego znaczenia ploidii są wśród badaczy podzielone. Celem pracy była ocena wpływu nieprawidłowej ilości DNA w komórkach raka na wyniki odległe (10-letnie) leczenia chirurgicznego raka płaskonabłonkowego płuca. Materiał i metody: Analizie poddano grupę 110 chorych leczonych operacyjnie z powodu raka płaskonabłonkowego płuca w latach 1995-1997. W badanej grupie było 95 mężczyzn i 15 kobiet w wieku 34-77 lat (średnia 60 lat). U 52 chorych wykonano lobektomię, u 47 pneumonektomię, a u 11 inne resekcje. Większość chorych operowano w stadium IB (35 chorych), IIB (26 pacjentów) i IIIA (22 chorych). Badany materiał stanowiły preparaty parafinowe, w których metodą cytometrii przepły-wowej zbadano zawartość DNA w komórkach raka. W każdym przypadku oznaczono indeks DNA, a ilość DNA w komórkach nowotworowych zilustrowano w postaci histogramów. Analizę statystyczną przeprowadzono przy użyciu program komputerowy Statistica 10.0 i oraz StatXact 8. Wyniki: Odsetek przypadków aneuploidalnych (z nieprawidło-wą ilością DNA) wyniósł 44,5%. Nie stwierdzono korelacji mię- AbstractBackground: The biological variability of lung cancer is one of the causes of the unpredictable clinical outcome of the disease. Many investigators have devoted a lot of effort to finding molecular and biochemical prognostic factors that may prove helpful in the qualification of patients for postoperative chemotherapy. Notwithstanding various previous studies attempted to associate DNA quantification in cancer cells with the prognosis for lung cancer, there is a divergence of opinion about its value. The aim of the present study was to assess the impact of aneuploidy on late (10-year) survival in a group of patients treated surgically for squamous cell lung cancer. Material and methods: We analyzed a group of 110 patients surgically treated for squamous cell lung cancer between 1995 and 1997. The group consisted of 95 men and 15 women, aged between 34 and 77 years (the average age being 60). We performed lobectomy in 52 cases, pneumonectomy in 47 cases, and other resections in 11 patients. Most of the patients were in IB (35 cases), IIB (26 patients) and IIIA (22 cases

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Section: Discussionmentioning

confidence: 99%

TORAKOCHIRURGIA DNA ploidy as an independent prognostic factor: 10-year results in a group of patients surgically treated for squamous cell lung cancer

Kasprzyk¹,

Dyszkiewicz²,

Roszak³

et al. 2012

kitp

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“…The S phase (synthesis phase) is the part of the cell cycle in which DNA is replicated, occurring between the G1 and G2 phase, which is a reliable marker to indicate how fast a tumor is growing. In clinical practice, the S phase fraction could be used as an independent prognostic factor in node-negative invasive breast carcinoma (18). The proliferative index (PI) is a measure of the number of proliferated cells in a tumor, which is also an indicator of the cell proliferation rate.…”

Section: Discussionmentioning

confidence: 99%

Expression of connexin 32 and connexin 43 in acute myeloid leukemia and their roles in proliferation

Yan¹,

Chen²,

Lu³

et al. 2012

Oncology Letters

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Abstract. Connexins (Cxs), a conserved family of transmembrane proteins, function in the organization of cell-cell communicatin via gap junctions in multicellular organisms. However, the role of Cxs in acute myeloid leukemia (AML) is poorly understood. In this study, we investigated the relationship between cell proliferation and expression of connexin 43 (Cx43) and connexin 32 (Cx32) mRNA and proteins in acute myeloid leukemia in vitro. Proliferation was observed using a growth curve and the rate of proliferation was detected by MTT assay in the acute myeloid leukemia cell lines OCI-AML3 and OCIM2. Cell cycle and cell proliferation index were assessed by flow cytometry analysis. The mRNA expression of the gap junction genes Cx43 and Cx32 was detected by RT-PCR. The expression of Cx43 and Cx32 proteins in the cell lines was analyzed by western blot analysis and immunofluorescence. The doubling time of OCI-AML3 and OCIM2 was 48 h and 36 h, respectively. In OCIM2, the percentage of cells in the S phase fraction was 59.47±9.6%, and the proliferation rate was 78.12±8.9%; however, in OCI-AML3, the percentage of cells in the S phase was 24.95±5.8%, and the proliferation rate was 35.21±6.7%. At the mRNA level, both cell lines expressed Cx43 and Cx32, and there was no significant difference in the expression of Cx43 and Cx32 mRNA in the two cell lines. At the protein level, there was a significant difference in the expression of Cx43, but not of Cx32. The proliferation ability of OCIM2 was higher than OCI-AML3, and OCIM2 exhibited higher Cx43 western blot and fluorescence intensities compared with OCI-AML3. The results suggest that a higher expression of Cx43 in AML cells may play a significant role in the proliferation ability.

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“…The study concluded that the ploidy pattern and SPF in metastatic nodes might be considered as a discriminate measure for risk factors in breast cancer patients with positive axillary nodes. Moureau-Zabotto et al [43] suggested that a combination of DNA ploidy and SPF predict patient outcome particular in lymph node breast cancer patients. So, DNA ploidy results can be combined with other features in efficient evaluation of prognosis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of DNA Image Cytometry in Libyan Breast Cancer

et al. 2012

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Background: We evaluated the relation of nuclear DNA content and clinicopathological features and prognosis in primary breast cancer of female Libyan patients with variable stage and grade and different treatment regimes. Patients and Methods: Histological samples from 104 patients of breast carcinoma were retrospectively studied by computerized nuclear DNA cytometry. Isolated nuclei from paraffin sections were stained with Feulgen stain and DNA was measured using a computer-assisted image analysis cytometry system. In each case, 200 nuclei were measured and the DNA histograms, S phase fraction (SPF) and number of cells above 5c and 9c were determined. We applied different approaches in the analysis of DNA to compare the DNA histograms with different clinicopathological features and survival. Results: The mean of DNA ploidy mode for all tumors was 3.43; 82.7% of tumors were aneuploid and 17.3% were diploid. The median SPF was 3.5% for DNA diploid and 13.5% for DNA aneuploid tumors. DNA aneuploid tumors and high SPF were associated with advanced stage, distant metastasis, high histological grade and lymph node involvement. The SPF was also associated with large tumor size and with younger patients (<50 years). In the overall population (median follow-up 51 months), patients with aneuploid DNA histograms and high SPF values had shorter survival times than those with diploid DNA histograms and low SPF values (p = 0.001, p < 0.0001, respectively). Also, short survival was associated with a multiploid DNA histogram and with DNA aneuploid cells ≥5 cells (p < 0.0001, p = 0.001, respectively). In a Cox multivariate analysis, DNA ploidy (p = 0.010), age (p = 0.038) and clinical stage (p = 0.001) were independent predictors of overall survival, and DNA ploidy (p = 0.018) and clinical stage (p = 0.001) also proved to be independent predictors of disease-specific survival. The SPF cutoff point of 11% might be applied to separate patients into good and poor prognosis groups. Conclusions: DNA image cytometry with careful analysis of the histograms may provide valuable prognostic information in Libyan breast cancer, with potential clinical implications in patient management, particularly in predicting the patients at high risk for metastasis and recurrence who should be considered as candidates for combined adjuvant therapy.

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Combined flow cytometry determination of S-phase fraction and DNA ploidy is an independent prognostic factor in node-negative invasive breast carcinoma: analysis of a series of 271 patients with stage I and II breast cancer

Cited by 27 publications

References 34 publications

TORAKOCHIRURGIA DNA ploidy as an independent prognostic factor: 10-year results in a group of patients surgically treated for squamous cell lung cancer

TORAKOCHIRURGIA DNA ploidy as an independent prognostic factor: 10-year results in a group of patients surgically treated for squamous cell lung cancer

Expression of connexin 32 and connexin 43 in acute myeloid leukemia and their roles in proliferation

Prognostic Significance of DNA Image Cytometry in Libyan Breast Cancer

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