A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays

Charpin, Colette; Secq, Véronique; Giusiano, Sophie; Carpentier, Samuel; Andrac, L; Lavaut, Marie‐Noëlle; Allasia, Claude; Bonnier, Pascal; García, Stéphane

doi:10.1002/ijc.24177

Cited by 55 publications

(72 citation statements)

References 51 publications

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“…The procedure for construction of TMAs was as previously described (22,27,28,42,43). Briefly, cores were punched from the selected 667 paraffin blocks, and distributed in three new blocks including two cores of 0.6 mm diameter for each tumour (about 220 cases per block).…”

Section: Methodsmentioning

confidence: 99%

“…Serial tissue sections were prepared 24 h before immunohistochemical processing and stored at 4˚C, as previously reported (22)(23)(24)(25)(26)(27)(28)42,43). The immunoperoxidase procedure was performed using an automated Ventana Benchmark XT device which allowed similar well controlled antigen retrieval for all tumours, and Ventana kits.…”

Section: Methodsmentioning

confidence: 99%

“…When significant differences in mean quantitative scores of expression were identified between patients with or without distant metastasis or death (Mann-Whitney tests), the prognostic relevance was re-evaluated for each marker using log-rank test (Kaplan-Meier curves). The distribution and relationship of prognostic markers were then documented through supervised hierarchical clusters and dendrograms, as previously reported (27,28,42,43).…”

Section: Methodsmentioning

confidence: 99%

“…We used the SAMBA/TRIBVN device (22)(23)(24)(25)(26)(27)(28)) that provides accurate numerical data for statistical analysis of continuous variables, with high-throughput assays using TMAs (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41) in a large retrospective series (n=667) of node-negative breast carcinomas. We have recently reported our experience with this standardised method for quantifying immunoprecipitates (42,43), which proved to be of potential clinical relevance through identification of immunohistochemical signatures of prognosis. However, methods relying upon dichotomising continuous predictors (42,43), using cut-points in logistic regression are controversial (14)(15)44,45).…”

Section: Introductionmentioning

confidence: 99%

“…We have recently reported our experience with this standardised method for quantifying immunoprecipitates (42,43), which proved to be of potential clinical relevance through identification of immunohistochemical signatures of prognosis. However, methods relying upon dichotomising continuous predictors (42,43), using cut-points in logistic regression are controversial (14)(15)44,45). Therefore, in the present study, we correlated the quantified immunohistochemical expression of each marker, then of groups of markers (referred to as immunohistochemical signatures), with the patient outcome (mean follow-up 102 months), in order to identify the combination of markers with the best sensitivity and specificity to predict prognosis in terms of occurrence of early distant metastases, using a multivariable fractional polynomials method (46,47).…”

Section: Introductionmentioning

confidence: 99%

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Immunohistochemical profiling of node negative breast carcinomas allows prediction of metastatic risk

Giusiano

Secq²,

Carcopino³

et al. 2010

Int J Oncol

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Abstract. The aim of this study was to identify a prognostic immunohistochemical signature indicative of risk of early metastasis in node-negative breast carcinomas that would also be relevant to the development of new tailored therapy. Quantitative measurements of the immunohistochemical expression of 64 markers (selected from literature data) using high-throughput densitometry (as a continuous variable) of digitised microscopic micro-array images were correlated with clinical outcome in 667 node-negative breast carcinomas (mean follow-up 102 months). Multivariable fractional polynomials model of logistic regression allowed the selection of the best combination of markers (in terms of sensitivity and specificity) to predict patient outcome without any categorisation using predefined cut-points for individual marker measurements. A highly predictive ten-marker (out of 64) signature was identified comprising PI3K, pmTOR, pMAPKAPK-2, SHARP-2, P21, HIF-1·, Moesin, p4 E BP-1, pAKT and P27 that well classified 91.4% of node-negative patients (specificity 90.9%, sensitivity 93.7%, area under ROC curve 0.958) independently of estrogen receptors (ER), and progesterone receptors (PR) and HER-2 status (91.6% well classified patients when ER, PR, HER-2 excluded). It is concluded that quantitative immunoprofiling of node-negative breast carcinomas is helpful in selecting patients who should not receive aggressive adjuvant chemotherapy and provides data for the development of tailored therapy.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Immunohistochemical profiling of node negative breast carcinomas allows prediction of metastatic risk

Giusiano

Secq²,

Carcopino³

et al. 2010

Int J Oncol

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Synthesis and study of new radial organic/inorganic hybrid epoxides

Herr¹,

Chaplinsky²,

Romanelli³

et al. 2007

J of Applied Polymer Sci

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A new approach to the synthesis of reactive organic/inorganic hybrid molecules was developed. Alternating hydrocarbon and siloxane segments were introduced into the arms of radial oligomers using hydrosilation chemistry. Cycloaliphatic and glycidyl epoxy-terminal systems with bisphenol A-based aromatic hydrocarbon cores and siloxane units derived from 1,1,3,3-tetramethyldisiloxane were synthesized and fully characterized (molecules 7 and 6, respectively). The cationic UV and thermal curing behavior of these two new radial hybrid epoxies was investigated using photo-and thermal-differential scanning calorimetry. Hybrid cycloaliphatic epoxy 7 exhibited good UV curing kinetics and photopolymerized to high conversion. The glycidyl analog 6 exhibited poor UV curing kinetics, but was readily cured using 2-ethyl-4-methylimidazole as a nucleophilic curing agent. Both hybrid epoxysiloxanes exhibited extensive thermal cationic cure. The physical properties of cured films of the two new radial epoxysiloxanes were studied and compared with various commercially available hydrocarbon and siloxane benchmark materials. The cured systems exhibited lower moisture uptake and better thermal stability than most hydrocarbon epoxies examined. Several visually compatible blends of the new hybrid molecules with common hydrocarbon resins were identified, and in general organic compatibility was found to be intermediate among selected siloxane-containing benchmarks. Molecules 6 and 7 represent progress towards the goal of synthesizing highly functional organic/inorganic hybrid molecules which combine the best attributes of both hydrocarbon epoxides and siloxane materials.

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Validation of an immunohistochemical signature predictive of 8‐year outcome for patients with breast carcinoma

Charpin

Tavassoli

Secq

et al. 2012

Intl Journal of Cancer

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We recently reported that standardized quantitative immunohistochemical (IHC) assays allowed prediction of an adverse outcome among 572 node negative (N2) patients with breast carcinoma (BrCa). To further validate our prior findings, we repeated the IHC stains including a second series of BrCa diagnosed at Yale University. Tissue microarrays (TMAs) of two cohorts of patients with BrCa (418 Marseille University and 303 Yale University) were respectively investigated for IHC expression of 15 markers (HIF-1a, PI3K, pAKT, pmTOR, moesin, P21, 4 E BP-1, P27, Ker5-6, pMAPKAPK-2, SHARP2, claudin-1, ALDH, AF6 and CD24). Quantitative measurements of immunoprecipitates densitometry assessed with an image analyzer were correlated with 8-year patients' outcome and compared in the two cohorts. The best predictive signature consisted of a combination of five markers that included HIF-1a, PI3K, claudin-1, AF6 and pAKT in N2 BrCa. This combination permitted an accurate prediction of outcome in 92.34% (386/418) of N2 patients in the first set (Marseille) and 89.8% (158/176) in the second set (Yale). The close results in both cohorts confirmed the validity of this original IHC signature predictive of prognosis in node negative BrCa. This validation suggests that in clinical practice, it would be possible with standardized kits (i) to identify patients with poor prognosis at diagnosis time, particularly in the N2 BrCa subset, who would require more aggressive adjuvant therapy and (ii) to avoid useless expensive therapies and their side effects in N2 patients with favorable prognosis.Widespread screening programs in western countries have significantly improved early detection of breast carcinoma (BrCa) resulting in an increased incidence of early stages of tumors. Furthermore, significant improvements in management of node negative (NÀ) patients have resulted in longer survival and better quality of life after therapy. It is widely acknowledged that NÀ BrCa may now tend to have a fairly good overall survival rate since only 30-40% of patients develop distant metastases.1 According to current guidelines and since there are no means of clearly identifying patients who will not relapse, hence should not receive adjuvant chemotherapy, most patients are offered chemotherapy leading to overtreatment of a large proportion.2,3 Clearly, markers permitting the identification of patients not requiring aggressive adjuvant therapy are urgently needed to avoid unnecessary exposure of women to the potential toxicity of such treatments, and also to reduce the overall cost of BrCa management.

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A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays

Cited by 55 publications

References 51 publications

Immunohistochemical profiling of node negative breast carcinomas allows prediction of metastatic risk

Immunohistochemical profiling of node negative breast carcinomas allows prediction of metastatic risk

Synthesis and study of new radial organic/inorganic hybrid epoxides

Validation of an immunohistochemical signature predictive of 8‐year outcome for patients with breast carcinoma

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