HER-2/<i>neu</i>Testing Comes of Age

Wisecarver, James L.

doi:10.1093/ajcp/111.3.299

Cited by 34 publications

(20 citation statements)

References 6 publications

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“…To quantify M68 protein expression in tumors, a scoring system was developed based on the validated system for HER-2͞neu, a protein overexpressed in a subset of human breast and ovarian tumors (16). Slides were scored on a four-point scale (Fig.…”

Section: Resultsmentioning

confidence: 99%

Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster

Bai

Connolly

Metzker

et al. 2000

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

206

165

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Fas-mediated apoptosis is an important regulator of cell survival, and abnormalities in this system have been shown to result in a number of human pathological conditions. A secreted member of the tumor necrosis factor receptor superfamily, DcR3, was recently reported to be amplified in human lung and colon cancers as a negative regulator of Fas-mediated apoptosis. We identified this gene, which we call M68. M68 genomic DNA, mRNA, and protein levels were examined in a series of human gastrointestinal tract tumors. Using M68 immunohistochemistry and a scoring system similar to that used for HER-2͞neu, we found that M68 protein was overexpressed in 30 of 68 (44%) human adenocarcinomas of the esophagus, stomach, colon, and rectum. Tumors examined by Northern blot revealed M68 mRNA highly elevated in a similar fraction of primary tumors from the same gastrointestinal tract regions, as well as in the colon adenocarcinoma cell lines SW480 and SW1116. Further, we found M68 protein to be overexpressed in a substantial number of tumors in which gene amplification could not be detected by fluorescence in situ hybridization or quantitative genomic PCR, suggesting that overexpression of M68 may precede amplification in tumors. Finally, we find that M68 lies within a four-gene cluster that includes a novel helicase-like gene (NHL) related to RAD3͞ERCC2, a plasma membrane Ras-related GTPase and a member of the stathmin family, amplification or overexpression of which may also contribute to cell growth and tumor progression.

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Section: Resultsmentioning

confidence: 99%

Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster

Bai

Connolly

Metzker

et al. 2000

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

206

165

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“…20 But it is still controversial which detection method should be preferred for the evaluation of the c-erbB2/Her-2/neu status of a tumor. 43 Especially small lesions (like atypical ductal hyperplasia and ductal carcinoma in situ) are difficult to study using fluorescence in situ hybridization. Besides the often poor preservation of morphological details after hybridization and the technical difficulties with reproducible quantification of hybridization signals (especially from low-level amplifications) the greatest limitation of the fluorescence in situ hybridization technique is the very restricted availability of standardized probes.…”

Section: Discussionmentioning

confidence: 99%

Detection of Gene Amplification in Archival Breast Cancer Specimens by Laser-Assisted Microdissection and Quantitative Real-Time Polymerase Chain Reaction

Lehmann

Glöckner

Kleeberger

et al. 2000

The American Journal of Pathology

128

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“…HER2 is an important member of the HER family and frequently overexpressed or amplified in a number of tumor types [28,46,52]. HER2 overexpression or HER2 gene amplification is found in up to 30% of breast cancers, leading to aggressive behavior and an unfavorable prognosis.…”

Section: Therapeutic Strategies To Target Molecules and Developmementioning

confidence: 99%

“…The presence or absence of overexpressed HER2 protein or HER2 gene amplification are used to differentiate patients who may have a response to the humanized antibody from those who do not have a response. Although several IHC based assays and only one FITC assay are available for determining eligibility for the Herceptin therapy, the FISH assay is not widespread in Japan due to practical and economical reasons [46,52].…”

Section: Development Of Pharmdx Tests For Therapeutic Monoclonalmentioning

confidence: 99%

“…Molecular or histochemical testing may help to identify predisposition to cancers, determine the onset of cancers for earlier intervention, and select the target for the most effective treatment. For the success of the targeted therapies, identification of patients bearing a target molecule, or activated target molecule is an absolute prerequisite for determining patient eligibility [10,28,46,52]. Progressive molecular biotechnologies based on immunohistochemistry (IHC) and in situ hybridization (ISH) techniques have provided a variety of beneficial means to identify tumor biology factors such as HER1 (EGFR), HER2, and KIT [17,23,47].…”

Section: Introductionmentioning

confidence: 99%

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Development of Precise Pharmocodiagnostic (PharmDx) Tests for Molecular Targeted Therapies

Tani¹,

Hatanaka²,

Hashizume³

2005

Acta Histochem. Cytochem

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HER-2/neuTesting Comes of Age

Cited by 34 publications

References 6 publications

Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster

Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster

Detection of Gene Amplification in Archival Breast Cancer Specimens by Laser-Assisted Microdissection and Quantitative Real-Time Polymerase Chain Reaction

Development of Precise Pharmocodiagnostic (PharmDx) Tests for Molecular Targeted Therapies

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