Analysis of HER2 by chromogenic in situ hybridization and immunohistochemistry in lymph node–negative breast carcinoma: prognostic relevance

Peiró, Gloria; Aranda, Ignacio; Adrover, Encarna; Niveiro, M.; Alenda, Cristina; Payá, Artemio; Seguí, J

doi:10.1016/j.humpath.2006.07.013

Cited by 17 publications

(19 citation statements)

References 33 publications

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“…However, because the commonly accepted testing algorithm for HER-2 uses fluorescence in situ hybridization only in equivocal cases with an immunohistochemical score of 2+ (23), we only used fluorescence in situ hybridization in the 2+ cases in the present study. A similar algorithm has recently been proposed by Peiro and coworkers (24). However, these authors forwent to test for its prognostic significance.…”

Section: Discussionmentioning

confidence: 98%

Prognostic Effect of Epithelial Cell Adhesion Molecule Overexpression in Untreated Node-Negative Breast Cancer

Schmidt¹,

Hasenclever

Schaeffer³

et al. 2008

Clinical Cancer Research

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Purpose: Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention not only as a prognostic factor in breast cancer but also as a potential target for immunotherapy. We examined Ep-CAM expression in 402 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting. Experimental Design: Ep-CAM expression was evaluated by immunostaining. Its prognostic effect was estimated relative to overexpression/amplification of HER-2, histologic grade, tumor size, age, and hormone receptor expression. Results: Ep-CAM status was positive in 106 (26.4%) patients. In multivariate analysis, Ep-CAM status was associated with disease-free survival independent of age, pT stage, histologic grade, estrogen receptor (ER), progesterone receptor (PR), as well as HER2 status (P = 0.028; hazard ratio, 1.60; 95% confidence interval, 1.05-2.44). Recently, so-called triple-negative (HER-2, ER, and PR) breast cancer has received increased attention. We noticed a similar association of Ep-CAM with disease-free survival in the triple-negative group as for the entire cohort. Conclusion: In this study of untreated breast cancer patients, Ep-CAM overexpression was associated with poor survival in the entire cohort and in the subgroup of triple-negative breast cancer. This suggests that Ep-CAM may be a well-suited target for specific therapies particularly in HER-2^, ER-, and PR-negative tumors.

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Section: Discussionmentioning

confidence: 98%

Prognostic Effect of Epithelial Cell Adhesion Molecule Overexpression in Untreated Node-Negative Breast Cancer

Schmidt¹,

Hasenclever

Schaeffer³

et al. 2008

Clinical Cancer Research

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“…31 Quantitative RT-PCR and DNA Sequencing DNA isolation method, PCR conditions, primers, as well as mutational and quantitative analyses of IGF1R have been described previously. 30 In brief, we extracted genomic DNA using the QIAmp DNA mini-kit, and isolated total RNA by handling the RNeasy formalin-fixed paraffin-embedded kit (Qiagen, Hilden, Germany) from 2-3 paraffin-embedded cylinders (1-mm thick) from preselected tumor areas with at least 30% tumor cell content.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Increased insulin-like growth factor-1 receptor mRNA expression predicts poor survival in immunophenotypes of early breast carcinoma

et al. 2011

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The biology of breast carcinoma shows a great variation, reflected by the recent classification of phenotypes based on DNA microarrays or immunohistochemistry. The aim of this study was to determine the prevalence of insulin-like growth factor-1 receptor (IGF1R) in breast carcinoma subtypes and the impact on the outcome. We studied 197 consecutive breast carcinoma patients in stage I-II treated conservatively. Phenotypes were assessed on the basis of the expressions of ER/PR, HER2, Ki67, p53, Bcl2, CK5/6 and EGFR. Moreover, IGF1R expression (a-subunit and b-phosphorylated/active form) was evaluated by immunohistochemistry, IGF1R mRNA levels by quantitative RT-PCR and IGF1R mutations by direct DNA sequencing. Overall, 40% (78/197) of tumors were luminal A, 24% (48/197) luminal B, 19% (37/197) HER2-positive and 17% (34/197) basal/triplenegative. Luminal A tumors were predominantly of low grade, without necrosis, presenting in older patients as a r2-cm unilateral mass (all Pr0.046). a-IGF1R overexpression was observed more frequently in luminal A (49%) cases, followed by luminal B (20%), HER2-positive area under the curve (22%) and basal/triple-negative cases (9%) (P ¼ 0.01) with similar results for mRNA levels (53, 24, 13 and 10%, respectively) (P ¼ 0.038), but without differences for mutations (P ¼ NS). High IGF1R mRNA correlated with poor patient survival among subtypes (P ¼ 0.004) (Kaplan-Meier; log-rank test). For overall survival, only histological grade and IGF1R mRNA emerged as significant predictors (Pr0.034; Cox regression). Increased IGF1R mRNA implies poorer patient prognosis among the different subtypes, and that may be associated with the lack of responsiveness to tamoxifen in cases with a positive hormone receptor status. Our results highlight the biological and clinical relevance of IGF1R in early breast carcinoma subtypes, and provide knowledge to assist in treatment decision.

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“…ER-positive/PR-negative tumors express higher levels of HER-1 and, especially, HER-2 and have more aggressive features than ER/PRpositive tumors [12,16]. Overexpression of receptors for growth factors such as HER-2 has also been shown to play an important prognostic role, independent of lymph node status, tumor size, or ER-status [17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Short-term outcome of primary operated early breast cancer by hormone and HER-2 receptors

Brouckaert

Pintens

Belle

et al. 2008

Breast Cancer Res Treat

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Introduction Prognostic subgroup classification of operable breast cancers using cDNA clustering of breast cancer-related genes resembles the classification based on the combined immunohistochemical (IHC) expression of the hormone and HER-2 receptors. We here report the shortterm disease-free interval (DFI) of operable breast cancers by their joint hormone receptor/HER-2 phenotype. Patients and methods Short-term follow-up (FU) of a prospective cohort of 1,958 breast-cancer patients primary operated at our institution between 2000 and 2005. Receptors were evaluated using IHC. Steroid receptors were considered positive for any nuclear staining; HER-2 for strong (3+) membrane staining or positive fluorescence in situ hybridization (FISH). Kaplan-Meier (KM) DFI curves were calculated for any relapse defined as a local, regional, contralateral, or distant breast cancer event for the six predefined breast cancer subgroups: ER + PR + HER-2 -(PPN), ER + PR -HER-2 -(PNN), ER + PR + HER-2 + (PPP), ER -PR -HER-2 -(NNN), ER -PR -HER-2 + (NNP), and ER + PR -HER-2 + (PNP). P-values were calculated for comparison of the six different survival curves using two possible adaptations for multiple testing. A multivariate model for the receptors predicting DFI did incorporate local and systemic adjuvant therapy. Results Median patient age was 57 years (ranges 26-96) and median FU was 3.35 years. Overall, DFI at median FU was 91%; 94% for PPN, 89% for PNN, 86% for NNN, 81% for PPP, 80% for PNP, and 76% for NNP cases. Some receptor subgroups had a significantly better DFI than others based on multiple testing, especially when the PPN group was compared against the four most frequent subtypes. The multivariate model with local and systemic adjuvant therapy confirmed the prognostic value of ER, PR, and HER-2 for short-term DFI. Conclusion It is possible to distinguish short-term prognostic breast cancer subgroups only on the basis of ER, PR, and HER-2 even when stratified for local and systemic adjuvant therapy. While gene expression profiles based on microarray data of over hundreds of genes will probably teach us much about breast cancer biology, heterogeneity, and prognosis, we emphasize the important short-term prognostic value of currently used IHC markers for ER, PR, and HER-2.

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Analysis of HER2 by chromogenic in situ hybridization and immunohistochemistry in lymph node–negative breast carcinoma: prognostic relevance

Cited by 17 publications

References 33 publications

Prognostic Effect of Epithelial Cell Adhesion Molecule Overexpression in Untreated Node-Negative Breast Cancer

Prognostic Effect of Epithelial Cell Adhesion Molecule Overexpression in Untreated Node-Negative Breast Cancer

Increased insulin-like growth factor-1 receptor mRNA expression predicts poor survival in immunophenotypes of early breast carcinoma

Short-term outcome of primary operated early breast cancer by hormone and HER-2 receptors

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