Clinical Research Papers:

Ideal number of biopsy tumor fragments for predicting HER2 status in gastric carcinoma resection specimens

Sangjeong Ahn _, Soomin Ahn, Michael Van Vrancken, Minju Lee, Sang Yun Ha, Hyuk Lee, Byung-Hoon Min, Jun Haeng Lee, Jae J. Kim, Sunkyu Choi, Sin-Ho Jung, Min Gew Choi, Jun-Ho Lee, Tae Sung Sohn, Jae Moon Bae, Sung Kim and Kyoung-Mee Kim

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Oncotarget. 2015; 6:38372-38380. https://doi.org/10.18632/oncotarget.5368

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Sangjeong Ahn1,6,*, Soomin Ahn1,2,*, Michael Van Vrancken1,*, Minju Lee1, Sang Yun Ha1, Hyuk Lee3, Byung-Hoon Min3, Jun Haeng Lee3, Jae J. Kim3, Sunkyu Choi4, Sin-Ho Jung4, Min Gew Choi5, Jun-Ho Lee5, Tae Sung Sohn5, Jae Moon Bae5, Sung Kim5, Kyoung-Mee Kim1,2

1Department of Pathology & Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

2Center for Companion Diagnostics, Innovative Cancer Medicine Institute, Samsung Medical Center, Seoul, Korea

3Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

4Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

5Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

6Present address: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine and BioMedical Research Institute, Pusan National University Hospital, Busan, Korea

*These authors have contributed equally to this work

Correspondence to:

Kyoung-Mee Kim, e-mail: [email protected]

Keywords: stomach, biopsy, operation, HER2, immunohistochemistry

Received: June 29, 2015     Accepted: September 29, 2015     Published: October 09, 2015


Intratumoral heterogeneity of HER2 expression is common in gastric cancers and pose a challenge for identifying patients who would benefit from anti-HER2 therapy. The aim of this study is to compare HER2 expression in biopsy and resection specimens of gastric carcinoma by immunohistochemistry (IHC) and to find the ideal number of biopsy tumor fragments that can accurately predict HER2 overexpression in the corresponding surgically resected specimen. The HER2 IHC results of 702 paired biopsy and resection specimens of gastric cancer were compared.

The mean number of biopsy fragments among all cases was 4.3 (range 1–11). HER2 was positive in 130 (18.5%) endoscopic biopsies and in 102 (14.5%) gastrectomy specimens. Intratumoral heterogeneity of HER2 was found in 80 (61.5%) biopsies and 70 (68.6%) resection specimens. Out of the 70 surgical specimens with intratumoral heterogeneity, 24 (34.3%) of the corresponding biopsies were categorized as negative (positive conversion). In the 86 (12.3%) discrepant cases, negative conversion was observed in 57 (66.3%) cases and positive conversion in 29 (33.7%). The fragment numbers were significantly correlated with the discrepancy of results and positive predictability (P = 0.0315 and P = 0.0052). ROC curve analysis and positive predictability showed that 4 fragments should be obtained to minimize the differences in HER2 scores between biopsy and resection specimen.

In gastric carcinomas with discrepant HER2 results between biopsy and surgical resection specimens, intratumoral heterogeneity is common with most of them showing positive conversion. To predict HER2 status precisely, at least 4 biopsy fragments containing tumor cells are required.

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