Short-term significance of DNA ploidy and cell proliferation in breast carcinoma: a multivariate analysis of prognostic markers in a series of 308 patients.

Pinto, António E.; André, Saudade; Soares, Jorge

doi:10.1136/jcp.52.8.604

Cited by 50 publications

(70 citation statements)

References 55 publications

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“…A consistent result from our previous cytometric studies was the significant correlation between DNA aneuploidy/high SPF and a high grade of tumour differentiation (P<0.001) (7,8,11), greater tumour size (P<0.002) (7), lack of hormone (oestrogen and progesterone) receptors (P<0.001) (7,8,11) and human epidermal growth factor expression-2 (HER-2; P<0.001) (27). In addition, no significant association between DNA ploidy/SPF and axillary lymph node status was identified (7,8,11,27).…”

Section: Association Between Dna Ploidy/spf and The Histopathologicasupporting

confidence: 72%

“…In previous studies performed at the Portuguese Institute of Oncology of Lisbon, there was systematic focus on the application of survival analysis methods, including the following: Sample size; length of follow-up time; definition of the end points of interest; and the choice and quality of the univariate, multivariate and graphical analyses (7,8,11). The statistical power of survival studies depends on the accurate assessment of these variables, in order to prevent statistical inadequacies (26).…”

Section: Survival Analysismentioning

confidence: 99%

“…Numerous studies have reported that DNA ploidy and/or SPF are prognostic markers for breast cancer (2)(3)(4)(5)(6)(7)(8)(9)(10)(11); however, a number of studies have questioned their independent prognostic significance (12)(13)(14)(15). These conflicting data have limited the prognostic value of DNA flow cytometry and the extent of its clinical use.…”

Section: Introductionmentioning

confidence: 99%

“…In breast cancer, DNA ploidy and SPF have been investigated in association with the biological characterization of tumours, patient survival and prognosis (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

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Prognostic relevance of DNA flow cytometry in breast cancer revisited: The 25-year experience of the Portuguese Institute of Oncology of Lisbon

et al. 2017

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Abstract. The potential prognostic significance of DNA flow cytometric measurements (DNA ploidy and S-phase fraction) in breast cancer remains in dispute. Inconclusive data, primarily due to the lack of consistent standardization and quality control programs, have limited its translation into clinical practice. The aim of the present review, based on the 25-year experience of the Portuguese Institute of Oncology of Lisbon, is to assess the clinical relevance and application of DNA flow cytometry for the prognosis of breast cancer. Overall, data from Portuguese Institute of Oncology of Lisbon indicate that DNA flow cytometry provides significant prognostic information that is biologically relevant and clinically useful for the management of patients with breast cancer. Furthermore, this data has demonstrated the independent value of DNA aneuploidy as a prognostic indicator of poor clinical outcome in various subgroups of patients with early or locally advanced breast cancer at short-and long-term follow-up. Notably, aneuploidy identifies subsets of patients with grade (G)1 or G2 tumours who exhibit a poor clinical outcome. These patients may benefit from adjuvant chemotherapy, particularly those with luminal A and luminal B/human epidermal growth factor-2-negative endocrine-responsive breast cancer. In conclusion, data from Portuguese Institute of Oncology of Lisbon reinforces the clinical importance and utility of DNA flow cytometric analysis, particularly DNA ploidy, in the prognostic assessment and therapeutic planning for patients with breast cancer.

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Section: Association Between Dna Ploidy/spf and The Histopathologicasupporting

confidence: 72%

Section: Survival Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prognostic relevance of DNA flow cytometry in breast cancer revisited: The 25-year experience of the Portuguese Institute of Oncology of Lisbon

et al. 2017

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“…The sporadic series and 15 familial PTCs were analysed on representative fresh/ frozen samples of tumour specimens obtained at surgical resection, according to a technique described previously (32), which uses propidium iodide (Sigma) as fluorochrome for DNA staining, and RNase (Sigma) and non-ionic detergent Nonidet P40 (Sigma) for double-stranded RNA digestion and cell membrane lysis respectively. The remaining 29 familial PTC cases were assessed on formalin-fixed paraffin-embedded material following the technique of Hedley et al (33), with slight modifications, such as the thickness of block cut section (50 mm) and the incubation period for DNA staining (overnight).…”

Section: Dna Flow Cytometrymentioning

confidence: 99%

Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical/prognostic behaviour

Pinto

Silva²,

Henrique

et al. 2014

European Journal of Endocrinology

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Objective: Familial non-medullary thyroid cancer has been proposed as an aggressive clinical entity. Our aim in this study is to investigate potential distinguishing features as well as the biological and clinical aggressiveness of familial vs sporadic papillary thyroid carcinoma (PTC). We assessed clinicopathological characteristics, outcome measures and DNA ploidy. Design: A matched-case comparative study. Methods: A series of patients with familial PTC (nZ107) and two subgroups, one with three or more affected elements (nZ32) and another including index cases only (nZ61), were compared with patients with sporadic PTC (nZ107), matched by age, gender, pTNM disease extension and approximate follow-up duration. Histological variant, extrathyroidal extension, vascular invasion, tumour multifocality and bilateral growth were evaluated. Ploidy pattern was analysed in available samples by DNA flow cytometry. The probabilities of disease-free survival (DFS) and overall survival (OS) were estimated according to the Kaplan-Meier (K-M) method. Results: No patient with familial PTC died of disease during follow-up (median, 72 months), contrarily to five patients (4.7%) (PZ0.06) with sporadic PTC (median, 90 months). There was a significantly higher tumour multifocality in familial PTC (index cases subgroup) vs sporadic PTC (PZ0.035), and a trend, in the familial PTC cohort with three or more affected elements, to show extrathyroidal extension (PZ0.054) more frequently. No difference was observed in DNA ploidy status. The K-M analyses showed no significant differences between both entities in relation to DFS or OS. Conclusion: Apart from multifocality, familial PTC appears to have similar clinical/prognostic behaviour when compared with sporadic forms of the disease.

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The combination of insulin‐like growth factor 1 and osteogenic protein 1 promotes increased survival of and matrix synthesis by normal and osteoarthritic human articular chondrocytes

Loeser¹,

Pacione²,

Chubinskaya³

2003

Arthritis & Rheumatism

172

140

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Objective. Although growth factor therapy could be an attractive method for stimulating the repair of damaged cartilage matrix, there is evidence that with aging and/or with the development of osteoarthritis (OA), articular chondrocytes may become unresponsive to growth factor stimulation. The aim of the current study was to compare the ability of insulin-like growth factor 1 (IGF-1) and osteogenic protein 1 (OP-1), alone and in combination, to stimulate human normal and OA chondrocytes in culture.Methods. Chondrocytes isolated by enzymatic digestion of cartilage obtained from subjects undergoing knee replacement for OA (n ‫؍‬ 6) or from normal ankle joints of tissue donors (n ‫؍‬ 7) were cultured in alginate beads in serum-free medium and treated for 21 days with 100 ng/ml IGF-1, 100 ng/ml OP-1, or both. Controls were treated with vehicle alone. The cultures were evaluated for cell survival, cell number by DNA analysis, matrix production by particle exclusion assay, and level of accumulated proteoglycan by dimethylmethylene blue assay.Results. After 21 days in serum-free alginate culture, survival of cells from OA cartilage was 65 ؎ 2% (mean ؎ SEM), while survival of cells from normal cartilage was significantly greater (82 ؎ 3%). Treatment with either IGF-1 or OP-1 alone minimally improved survival, while the combination IGF ؉ OP significantly improved survival, to 87 ؎ 2% for OA cells and 95 ؎ 1% for normal cells. Cell proliferation was noted only in the IGF ؉ OP group; this was significant for both normal and OA cells (ϳ2-fold increase in DNA levels). Matrix production, assessed by particle exclusion and by proteoglycan accumulation, was greatest in the cells treated with IGF ؉ OP in both normal and OA cultures. When proteoglycan levels were corrected for cell numbers (g proteoglycan/ng DNA), a significant increase over control was noted with OP-1 alone and IGF ؉ OP, but not IGF-1 alone, in both normal and OA cultures, with the greatest levels in the combination group (3-fold increase over control).Conclusion. OP-1 was more potent than IGF-1 in stimulating proteoglycan production in both normal and OA cells. However, the best results were obtained with the combination, suggesting that combined therapy with IGF-1 and OP-1 may be an effective strategy for treating OA cartilage damage.

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Short-term significance of DNA ploidy and cell proliferation in breast carcinoma: a multivariate analysis of prognostic markers in a series of 308 patients.

Cited by 50 publications

References 55 publications

Prognostic relevance of DNA flow cytometry in breast cancer revisited: The 25-year experience of the Portuguese Institute of Oncology of Lisbon

Prognostic relevance of DNA flow cytometry in breast cancer revisited: The 25-year experience of the Portuguese Institute of Oncology of Lisbon

Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical/prognostic behaviour

The combination of insulin‐like growth factor 1 and osteogenic protein 1 promotes increased survival of and matrix synthesis by normal and osteoarthritic human articular chondrocytes

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