Chromogenic in Situ Hybridization

Tanner, Minna; Gancberg, David; Leo, Angelo Di; Larsimont, Denis; Rouas, Ghizlane; Piccart, Martine; Isola, Jorma

doi:10.1016/s0002-9440(10)64785-2

Cited by 321 publications

(75 citation statements)

References 12 publications

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“…Evaluations were performed blinded to all clinical and biological variables. Methods for PTEN IHC, PIK3CA mutational screening, and HER2 chromogenic in situ hybridization have been described (16,38). Stathmin IHC is described in SI Methods.…”

Section: Methodsmentioning

confidence: 99%

Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity

Saal

Johansson²,

Holm³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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424

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Pathway-specific therapy is the future of cancer management. The oncogenic phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in solid tumors; however, currently, no reliable test for PI3K pathway activation exists for human tumors. Taking advantage of the observation that loss of PTEN, the negative regulator of PI3K, results in robust activation of this pathway, we developed and validated a microarray gene expression signature for immunohistochemistry (IHC)-detectable PTEN loss in breast cancer (BC). The most significant signature gene was PTEN itself, indicating that PTEN mRNA levels are the primary determinant of PTEN protein levels in BC. Some PTEN IHC-positive BCs exhibited the signature of PTEN loss, which was associated to moderately reduced PTEN mRNA levels cooperating with specific types of PIK3CA mutations and/or amplification of HER2. This demonstrates that the signature is more sensitive than PTEN IHC for identifying tumors with pathway activation. In independent data sets of breast, prostate, and bladder carcinoma, prediction of pathway activity by the signature correlated significantly to poor patient outcome. Stathmin, encoded by the signature gene STMN1, was an accurate IHC marker of the signature and had prognostic significance in BC. Stathmin was also pathway-pharmacodynamic in vitro and in vivo. Thus, the signature or its components such as stathmin may be clinically useful tests for stratification of patients for anti-PI3K pathway therapy and monitoring therapeutic efficacy. This study indicates that aberrant PI3K pathway signaling is strongly associated with metastasis and poor survival across carcinoma types, highlighting the enormous potential impact on patient survival that pathway inhibition could achieve.breast cancer ͉ metastasis ͉ stathmin ͉ microarray

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Section: Methodsmentioning

confidence: 99%

Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity

Saal

Johansson²,

Holm³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

470

424

View full text Add to dashboard Cite

show abstract

“…In several breast cancer studies, HER2 CISH correlated well with FISH and IHC [44, 46–51]. In gastric cancer, one study systematically analyzed the concordance between CISH and FISH assays and observed a perfect correlation in 128 samples [52].…”

Section: Human Epidermal Growth Factor Receptormentioning

confidence: 99%

HER-2/neuTesting and Therapy in Gastroesophageal Adenocarcinoma

Moelans

Diest

Milne

et al. 2011

Pathology Research International

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Despite ongoing advances in the treatment of gastroesophageal cancer, prognosis remains poor. The best promise to improve this poor survival is provided by new targeted agents. Of these, human epidermal growth factor receptor 2 (HER2) is currently in the spotlight. In this review, we provide an overview of recent developments in HER2 testing and results of clinical trials targeting HER2 in gastroesophageal adenocarcinoma. Based on the encouraging ToGA trial findings it is now expected that routine HER2 testing will be included in the diagnostic work-up of patients with advanced gastric cancer. With regard to this testing, overexpression of the HER2 protein seems to possess the best predictive properties. However, HER2 immunohistochemistry (IHC) is subject to assay and interobserver variability, so standardization and internal and external proficiency testing is an absolute prerequisite, especially as the IHC scoring system in gastric cancer is different from that of breast cancer. Further study is needed to investigate the clinical meaning of the significant heterogeneity observed in both gene amplification and protein overexpression in gastroesophageal cancer. Highly effective therapies for gastroesophageal cancer can only be accomplished by a multi-targeted approach, considering crosstalk between pathways and continuing to optimize chemotherapy.

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“…The utility of CISH has been investigated in several studies. Tanner and colleagues [28]analyzed freshly frozen tumor samples and archival formalin-fixed paraffin-embedded tissue sections by FISH, IHC and CISH. HER2 amplification determined by FISH and CISH was comparable and in general agreement with results for HER2 receptor overexpression obtained by IHC.…”

Section: Her2 Testingmentioning

confidence: 99%

Emerging Technologies for HER2 Testing

Vijver

2002

Oncology

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HER2-positive status is the sole criterion for identifying patients with breast cancer for Herceptin^® therapy, which has known efficacy in women with metastatic breast cancer (MBC). Immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH), which measure the HER2 protein and gene, respectively, are currently the most widely used HER2 tests in the clinical setting. However, results from these assays are influenced by many variables including choice of antibody or probe, methodology, level of user experience and interlaboratory variability. Although there is no widespread standard testing algorithm, the importance of HER2 in clinical practice demands accurate and reproducible tests. Polymerase chain reaction (PCR) and chromogenic in-situ hybridization (CISH) represent upcoming methods for assessing HER2 gene amplification. Enzyme-linked immunosorption assay (ELISA), a semi-automated technique that can be used to measure the level of the HER2 extracellular domain (ECD) in serum, may also prove useful. While such technologies show great promise, they will at least have to be validated against IHC or FISH before being accepted into routine clinical practice.

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Chromogenic in Situ Hybridization

Cited by 321 publications

References 12 publications

Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity

Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity

HER-2/neuTesting and Therapy in Gastroesophageal Adenocarcinoma

Emerging Technologies for HER2 Testing

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