BACKGROUND: In esophageal adenocarcinoma (EAC), concordance and prognostic significance of human epidermal growth factor 2 (HER-2) protein overexpression and gene amplification are equivocal, which led us to reevaluate this by immunohistochemistry (IHC) and in situ hybridization. METHODS: One hundred and fifty-four patients were included in a tissue micro array (TMA). HER-2 gene amplification was assessed by fluorescence and silver-enhanced in situ hybridization (FISH and SISH) and expression with the HercepTest™. RESULTS: HER-2 was amplified in 16% by SISH and 18% by FISH. HER-2 positivity (IHC 3+ or 2+ with ISH+) was seen in 12% and overexpression (IHC 2+/3+) in 14%. Concordance was 92% between SISH/IHC, 90% between FISH/IHC and 95% between SISH/FISH. All IHC 3+ cases were amplified by SISH and in 93% by FISH. Of the IHC 2+cases, this was 33% (SISH) and 50% (FISH). Of the IHC 1+ cases, still 6% (SISH) and 8% (FISH) showed amplification. HER-2 positivity, overexpression and amplification were all associated with poor cancer-specific survival, in univariate analysis. Furthermore, HER-2 positivity and amplification (SISH) were independently associated with poor survival (hazard ratio, HR 6.343; 95% CI 1.218-36.234; P = 0.029 and HR 3.231; 95% CI 1.092-9.563; P = 0.034). CONCLUSION: HER-2 positivity and gene amplification are fairly frequent and independently associated with poor survival.
BACKGROUND: In esophageal adenocarcinoma (EAC), concordance and prognostic significance of human epidermal growth factor 2 (HER-2) protein overexpression and gene amplification are equivocal, which led us to reevaluate this by immunohistochemistry (IHC) and in situ hybridization. METHODS: One hundred and fifty-four patients were included in a tissue micro array (TMA). HER-2 gene amplification was assessed by fluorescence and silver-enhanced in situ hybridization (FISH and SISH) and expression with the HercepTest™. RESULTS:HER-2 was amplified in 16% by SISH and 18% by FISH. HER-2 positivity (IHC 3+ or 2+ with ISH+) was seen in 12% and overexpression (IHC 2+/3+) in 14%. Concordance was 92% between SISH/IHC, 90% between FISH/IHC and 95% between SISH/FISH. All IHC 3+ cases were amplified by SISH and in 93% by FISH. Of the IHC 2+cases, this was 33% (SISH) and 50% (FISH). Of the IHC 1+ cases, still 6% (SISH) and 8% (FISH) showed amplification. HER-2 positivity, overexpression and amplification were all associated with poor cancer-specific survival, in univariate analysis. Furthermore, HER-2 positivity and amplification (SISH) were independently associated with poor survival (hazard ratio, HR 6.343; 95% CI 1.218-36.234; P = 0.029 and HR 3.231; 95% CI 1.092-9.563; P = 0.034). CONCLUSION:HER-2 positivity and gene amplification are fairly frequent and independently associated with poor survival.
Authors: Angela N Bartley; Mary Kay Washington; Christina B Ventura; Nofisat Ismaila; Carol Colasacco; Al B Benson; Alfredo Carrato; Margaret L Gulley; Dhanpat Jain; Sanjay Kakar; Helen J Mackay; Catherine Streutker; Laura Tang; Megan Troxell; Jaffer A Ajani Journal: Am J Clin Pathol Date: 2016-11-14 Impact factor: 2.493
Authors: Aafke Creemers; Eva A Ebbing; Thomas C Pelgrim; Sjoerd M Lagarde; Faridi S van Etten-Jamaludin; Mark I van Berge Henegouwen; Maarten C C M Hulshof; Kausilia K Krishnadath; Sybren L Meijer; Maarten F Bijlsma; Martijn G H van Oijen; Hanneke W M van Laarhoven Journal: Sci Rep Date: 2018-09-05 Impact factor: 4.379
Authors: Roelof J Beukinga; Da Wang; Arend Karrenbeld; Willemieke P M Dijksterhuis; Hette Faber; Johannes G M Burgerhof; Véronique E M Mul; Riemer H J A Slart; Robert P Coppes; John Th M Plukker Journal: Eur Radiol Date: 2020-11-05 Impact factor: 5.315