HER-2 amplification is highly homogenous in gastric cancer.
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HER-2 amplification is highly homogenous in gastric cancer. / Marx, Andreas; Tharun, Lars; Muth, Johanna; Dancau, Ana Maria; Simon, Ronald; Yekebas, Emre F.; Kaifi, Jussuf; Mirlacher, Martina; Brümmendorf, Tim; Bokemeyer, Carsten; Izbicki, Jakob R.; Sauter, Guido.
in: HUM PATHOL, Jahrgang 40, Nr. 6, 6, 2009, S. 769-777.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - HER-2 amplification is highly homogenous in gastric cancer.
AU - Marx, Andreas
AU - Tharun, Lars
AU - Muth, Johanna
AU - Dancau, Ana Maria
AU - Simon, Ronald
AU - Yekebas, Emre F.
AU - Kaifi, Jussuf
AU - Mirlacher, Martina
AU - Brümmendorf, Tim
AU - Bokemeyer, Carsten
AU - Izbicki, Jakob R.
AU - Sauter, Guido
PY - 2009
Y1 - 2009
N2 - Her-2 is the molecular target for antibody-based treatment of breast cancer (trastuzumab). The potential benefit of anti-Her-2 therapy is currently investigated in several other HER-2-amplified cancers including gastric cancer. Although HER-2 amplification occurs in more than 10% of gastric cancers, potential heterogeneity of HER-2 amplification and overexpression could represent a major drawback for anti-Her-2 therapy. To address the potential applicability of trastuzumab in gastric cancer, tissue microarray sections of 166 gastric adenocarcinomas and 69 lymph node metastases were analyzed for Her-2 overexpression and amplification using Food and Drug Administration-approved reagents for immunohistochemistry and fluorescence in situ hybridization. HER-2 amplification was seen in 27 (16%) of 166 gastric adenocarcinomas. Amplification was typically high level with more than 20 HER-2 copies per tumor cell and a HER-2/centromere 17 ratio >3. Amplification was associated with intestinal tumor phenotype but unrelated to survival, grading, pT, pN, or pM. Identical HER-2 status was found in primary tumor and their matched lymph node metastases. Moreover, HER-2 and Topoisomerase IIalpha coamplification analysis of 3 to 16 large sections from 8 Her-2-positive gastric cancers did not reveal any heterogeneity of the amplicon site. The high level of HER-2 amplification in combination with the homogeneity of its expression in primary and metastatic tumors argues for a possible therapeutic utility of trastuzumab in HER-2-amplified gastric adenocarcinomas.
AB - Her-2 is the molecular target for antibody-based treatment of breast cancer (trastuzumab). The potential benefit of anti-Her-2 therapy is currently investigated in several other HER-2-amplified cancers including gastric cancer. Although HER-2 amplification occurs in more than 10% of gastric cancers, potential heterogeneity of HER-2 amplification and overexpression could represent a major drawback for anti-Her-2 therapy. To address the potential applicability of trastuzumab in gastric cancer, tissue microarray sections of 166 gastric adenocarcinomas and 69 lymph node metastases were analyzed for Her-2 overexpression and amplification using Food and Drug Administration-approved reagents for immunohistochemistry and fluorescence in situ hybridization. HER-2 amplification was seen in 27 (16%) of 166 gastric adenocarcinomas. Amplification was typically high level with more than 20 HER-2 copies per tumor cell and a HER-2/centromere 17 ratio >3. Amplification was associated with intestinal tumor phenotype but unrelated to survival, grading, pT, pN, or pM. Identical HER-2 status was found in primary tumor and their matched lymph node metastases. Moreover, HER-2 and Topoisomerase IIalpha coamplification analysis of 3 to 16 large sections from 8 Her-2-positive gastric cancers did not reveal any heterogeneity of the amplicon site. The high level of HER-2 amplification in combination with the homogeneity of its expression in primary and metastatic tumors argues for a possible therapeutic utility of trastuzumab in HER-2-amplified gastric adenocarcinomas.
M3 - SCORING: Zeitschriftenaufsatz
VL - 40
SP - 769
EP - 777
JO - HUM PATHOL
JF - HUM PATHOL
SN - 0046-8177
IS - 6
M1 - 6
ER -