J Pathol Transl Med.  2016 Nov;50(6):436-441. 10.4132/jptm.2016.07.12.

Comparison of the FDA and ASCO/CAP Criteria for HER2 Immunohistochemistry in Upper Urinary Tract Urothelial Carcinoma

• Kim G
• Chung YR
• Kim B
• Song B
• Moon KC

• KMID: 2361991
• DOI: http://doi.org/10.4132/jptm.2016.07.12

Abstract

BACKGROUND
Human epidermal growth factor receptor 2 (HER2) is one of the known oncogenes in urothelial carcinoma. However, the association between HER2 and the prognosis of upper urinary tract urothelial carcinoma (UUTUC) has not yet been fully clarified. The aim of this study was to evaluate HER2 expression using the United States Food and Drug Administration (FDA) criteria and American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria and compare their prognostic significance in UUTUC.
METHODS
HER2 expression was evaluated in 144 cases of UUTUC by immunohistochemistry (IHC) using tissue microarrays. We separately analyzed HER2 expression using the FDA and ASCO/CAP criteria. The IHC results were categorized into low (0, 1+) and high (2+, 3+) groups.
RESULTS
Using the FDA criteria, 94 cases were negative, 38 cases were 1+, nine cases were 2+, and three cases were 3+. Using the ASCO/CAP criteria, 94 cases were negative, 34 cases were 1+, 13 cases were 2+, and three cases were 3+. Four cases showing 2+ according to the ASCO/CAP criteria were reclassified as 1+ by the FDA criteria. High HER2 expression by both the FDA criteria and ASCO/CAP criteria was significantly associated with International Society of Urological Pathology high grade (p = .001 and p < .001). The high HER2 expression group classified with the FDA criteria showed significantly shorter cancer-specific survival (p = .004), but the HER2 high and low expression groups classified with the ASCO/CAP criteria did not show significant differences (p = .161) in cancer-specific survival.
CONCLUSIONS
HER2 high expression groups were significantly associated with shorter cancer-specific survival, and our study revealed that the FDA criteria are more suitable for determining HER2 expression in UUTUC.

Keyword

Upper urinary tract urothelial carcinoma; HER2; FDA criteria; ASCO/CAP criteria

MeSH Terms

Humans
Immunohistochemistry*
Oncogenes
Pathology
Prognosis
Receptor, Epidermal Growth Factor
United States Food and Drug Administration
Urinary Tract*
Receptor, Epidermal Growth Factor

Figure

• 

  Fig. 1. Representative images of human epidermal growth factor receptor 2 (HER2) expression using the United States Food and Drug Administration criteria. (A, B) 1+ HER2 immunohistochemistry (IHC) positivity, faint membrane staining in more than 10% of tumor cells. (C, D) 2+ HER2 IHC positivity, moderate complete membrane staining in more than 10% of tumor cells. (E, F) 3+ HER2 IHC positivity, strong, complete membrane staining in more than 10% of tumor cells.

• 

  Fig. 2. One of four cases with discrepant scores according to the United States Food and Drug Administration (FDA) and American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2013 criteria. This case is classified as 2+ by the ASCO/CAP guidelines, showed moderate and “incomplete” membrane staining in more than 10% of tumor cells, and is classified as 1+ by the FDA guidelines due to the absence of “complete” membrane staining.

• 

  Fig. 3. Kaplan-Meier survival curves for cancer-specific survival. (A) Cancer-specific survival according to the International Society of Urological Pathology (ISUP) grade. (B) Cancer-specific survival according to the pTNM stage. (C) Cancer-specific survival according to human epidermal growth factor receptor 2 (HER2) expression by the United States Food and Drug Administration (FDA) criteria. (D) Cancer-specific survival according to HER2 expression by the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria.

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