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Evaluation of HER2 Protein Expression in Gastric Carcinomas: Comparative Analysis of 1414 Cases of Whole-Tissue Sections and 595 Cases of Tissue Microarrays

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Recent advances in molecular targeted therapy have identified HER2 as an important target for anti-cancer therapy in gastric cancer (GC). Although the clinical relevance and prognostic significance of HER2 in breast cancer has been well acknowledged, it remains controversial in GC.

Methods

HER2 expression was investigated in two independent series of GC by immunohistochemical staining. One series corresponded to 1,414 cases of whole-tissue sections and the other corresponded to 595 cases of tissue microarrays (TMAs). Results were compared and correlated with clinicopathologic parameters.

Results

HER2-positivity was detected in 12.3% of whole-tissue sections and 17% of TMAs. Among samples scored 3+, 90.1% stained ≥50% of the tumor area, but only 40.9% in score 2+ cases stained ≥50% of the tumor area. In whole-tissue sections, HER2-positivity was correlated with age (P = 0.002), histological type (differentiated or intestinal, P < 0.001), lymphovascular invasion (P = 0.005), and lymph node metastasis (P = 0.009). In TMAs, HER2-positivity was correlated only with age (P = 0.003) and histological type (P < 0.001). Multivariate analyses of the differentiated GC subgroup revealed that HER2-positivity was an independent poor prognostic factor (P = 0.042). The cases with HER2-positive in ≥50% of the tumor area showed worse prognosis than those of <50% (P = 0.021).

Conclusions

Despite discrepancies in the results from whole-tissue sections and TMAs, HER2 overexpression was positively correlated with aggressive biological behavior and was an independent poor prognostic factor for recurrence in differentiated GCs. Therefore, HER2-positive GCs should be considered for adjuvant trastuzumab therapy.

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Acknowledgment

Kab Choong Kim and Young Wha Koh contributed equally to this work. This study was supported by a grant (A081024) of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea.

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Authors and Affiliations

  1. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Kab Choong Kim MD, Tae Hwan Kim MD, Jeong Hwan Yook MD & Byung Sik Kim MD

  2. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Young Wha Koh MD, Se Jin Jang MD & Young Soo Park MD

  3. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Heung-Moon Chang MD

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  1. Kab Choong Kim MD
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Correspondence to Young Soo Park MD.

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10434_2011_1695_MOESM1_ESM.jpg

Supplementary Fig. Kaplan–Meier curves for RFS in relation to HER2-positivity: analyses of all histological types (differentiated and undifferentiated). There were no differences in RFS rate in whole tissue section series (a) and in TMA series (b)

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Kim, K.C., Koh, Y.W., Chang, HM. et al. Evaluation of HER2 Protein Expression in Gastric Carcinomas: Comparative Analysis of 1414 Cases of Whole-Tissue Sections and 595 Cases of Tissue Microarrays. Ann Surg Oncol 18, 2833–2840 (2011). https://doi.org/10.1245/s10434-011-1695-2

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