Prognostic comparative study of S-phase fraction and Ki-67 index in breast carcinoma

Pinto, António E.; André, Saudade; Pereira, Teresa; Nóbrega, S.; Soares, Jorge

doi:10.1136/jcp.54.7.543

Cited by 49 publications

(34 citation statements)

References 36 publications

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“…Numerous studies have reported that SPF is the most important predictor of survival in breast cancer (2,9,10,16,17). In the studies performed at the Portuguese Institute of Oncology of Lisbon, besides the prognostic significance of SPF in the subgroup of axillary node-positive patients (7), a comparison between SPF and Ki-67 expression for assessing tumour proliferative activity (25) revealed that only SPF had statistical significance for predicting disease outcome. Ki-67 expression analysis has the technical advantage of allowing the morphological evaluation of proliferating cell populations; however, there is still an important unresolved issue concerning the identification of the optimal Ki-67 cut-off value for discriminating between tumours with low and high proliferation (44,45).…”

Section: Discussionmentioning

confidence: 99%

“…SPF is a continuous biological variable rather than a dichotomous function; thus, each laboratory should establish its own SPF data (18). The current study used a median SPF value of 6.1% as the cut-off point to distinguish between tumours with low and high proliferative activity, as when distinct SPF variables were previously investigated, this cut-off value provided the highest prognostic significance (25). As recommended by previous studies (18)(19)(20), another approach to reporting SPF is the subdivision into tertiles (<4.5, 4.5-9.2 and ≥9.2%), which has been proven to possess prognostic significance (25).…”

Section: Methodsmentioning

confidence: 99%

“…The current study used a median SPF value of 6.1% as the cut-off point to distinguish between tumours with low and high proliferative activity, as when distinct SPF variables were previously investigated, this cut-off value provided the highest prognostic significance (25). As recommended by previous studies (18)(19)(20), another approach to reporting SPF is the subdivision into tertiles (<4.5, 4.5-9.2 and ≥9.2%), which has been proven to possess prognostic significance (25). However, as reported previously, a well-known limitation of SPF is the fact that in 20-25% of cases, primarily those with aneuploidy, determining SPF from the DNA histogram fails for the following technical reasons: i) Overlap of populations; ii) a high degree of background debris; iii) too few cells; and iv) tumour classification as multiploid and/or hypertetraploid (9,10).…”

Section: Methodsmentioning

confidence: 99%

“…An agreement in the proliferation data between the two methods was identified in 69.1% of cases (K statistic= 0.384). However, as a cell proliferation variable SPF, but not Ki-67 expression, demonstrated prognostic significance in regards to OS (P<0.0003) and DFS (P<0.0001) (25). Therefore, SPF appears to be a better prognostic indicator for breast cancer compared with Ki-67 expression (25).…”

Section: Prognostic Value Of Spf Compared With Ki-67 Expression In Brmentioning

confidence: 99%

“…In a study of 306 patients with primary operable breast cancer (disease stages I and II), flow cytometry and immunohistochemistry analysis were simultaneously performed in 230 cases (25). Cut-off points of 6.1% for SPF and 10% for Ki-67 expression were used to discriminate between tumours with low and high proliferation.…”

Section: Prognostic Value Of Spf Compared With Ki-67 Expression In Brmentioning

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: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Prognostic Value Of Spf Compared With Ki-67 Expression In Brmentioning

confidence: 99%

Section: Prognostic Value Of Spf Compared With Ki-67 Expression In Brmentioning

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 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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Synthesis of 3,3‐Disubstituted Oxindoles by Palladium‐Catalyzed Asymmetric Intramolecular α‐Arylation of Amides: Reaction Development and Mechanistic Studies

Katayev

Jia

Sharma

et al. 2013

Chemistry A European J

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Palladium complexes incorporating chiral N-heterocyclic carbene (NHC) ligands catalyze the asymmetric intramolecular α-arylation of amides producing 3,3-disubstituted oxindoles. Comprehensive DFT studies have been performed to gain insight into the mechanism of this transformation. Oxidative addition is shown to be rate-determining and reductive elimination to be enantioselectivity-determining. The synthesis of seven new NHC ligands is detailed and their performance is compared. One of them, L8, containing a tBu and a 1-naphthyl group at the stereogenic centre, proved superior and was very efficient in the asymmetric synthesis of fifteen new spiro-oxindoles and three azaspiro-oxindoles often in high yields (up to 99 %) and enantioselectivities (up to 97 % ee; ee=enantiomeric excess). Three palladacycle intermediates resulting from the oxidative addition of [Pd(NHC)] into the aryl halide bond were isolated and structurally characterized (X-ray). Using these intermediates as catalysts showed alkene additives to play an important role in increasing turnover number and frequency.

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Prognostic comparative study of S-phase fraction and Ki-67 index in breast carcinoma

Cited by 49 publications

References 36 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

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

Synthesis of 3,3‐Disubstituted Oxindoles by Palladium‐Catalyzed Asymmetric Intramolecular α‐Arylation of Amides: Reaction Development and Mechanistic Studies

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