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Discordance of HER2 expression in primary and metastatic upper gastrointestinal adenocarcinoma
Charlotta Hedner, Björn Nodin, Karin Jirström and Jakob Eberhard
Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Sweden
Conclusion
Background
Gastric cancer is the second most common cause of cancer-related death worldwide. The incidence is declining but the overall survival (OS) remains very poor, despite some progress in treatment strategies [1, 2]. Esophageal cancer is less common
but has an equally dismal OS [3] and the incidence is rising [4]. There is an evident need for better diagnostic, prognostic and
treatment tools.
Treatment with trastuzumab has in a large, randomized study been shown to improve survival rates for patients with HER2-overexpressing advanced gastric cancer [5], but the prognostic value of HER2 overexpression remains uncertain. Here, we examined the expression and prognostic value of HER2 in primary upper gastrointestinal adenocarcinoma, and concordance with
the expression in a subset of paired lymph node metastases.
Distribution of significant clinicopathological characteristics according to HER2 expression
• Discordant expression of HER2 in primary compared to metastatic adenocarcinoma
indicates that it is not sufficient to analyse HER2 overexpression in the primary
tumour alone.
• Given the higher proportion of HER2 overexpression in esophageal compared to
gastric adenocarcinoma, the potential benefit of treatment with trastuzumab
should be explored also in proximal esophageal adenocarcinoma.
HER2 expression
Factor n (%)
IHC 0-1 141(81)
IHC 2-3 33(19)
Differentiation grade
0.005
High
4 (3.2)
2 (8.3)
Intermediate
27 (21.8)
12 (50.0)
Low
93 (75.0)
10 (41.7)
Unknown
17
9
Location 3g
0.000
Esophageal
40 (28.6)
Material and methods
19 (63.3)
Cardiac
37 (26.4)
8 (26.7)
Gastric
63 (45.0)
3 (10.0)
Immunohistochemical HER2 expression was examined in tissue microarrays with all primary tumours and 81 paired lymph
node metastases from 175 patients with esophageal and gastric adenocarcinoma.
Unknown
1
3
Location 2g
Scoring criteria developed for gastric cancer were used and cases denoted as 2-3+ or 3+ were considered overexpressed. Kaplan Meier curves and log rank test were used to assess OS and recurrence free survival according to HER2 expression.
P
0.000
Esophageal
49 (35.0)
21 (70.0)
Gastric
91 (65.0)
9 (30.0)
Unknown
1
3
Results
Distribution of HER2 expression in primary tumours compared to lymph node metastases
HER2 was overexpressed in 33/174 (19.0%) or 17/174 (9.8%) primary cancers and 18/79 (22.8%) or 13/79 (16.5%) matched lymph node metastases. A positive conversion from primary tumour to lymph node metastasis was seen in 5/62 (8.1%)
cases and a negative conversion in 3/16 (18.8%) cases. HER2 overexpression was significantly correlated with a longer OS in
esophagus (p = 0.026), but HER2 overexpression had no other impact on OS or recurrence free survival, irrespective of tumour location. HER2 was overexpressed in 16.9 or 32.2% in esophageal cancers, 6.7 or 17.8 % in cardiac and 1.5 or 4.5 %
in gastric cancers.
Primary tumour
IHC 0-1
IHC 2-3
IHC 0-1
57 (91.9)
3 (18.8)
IHC 2-3
5 (8.1)
13 (81.2)
Total
62
16
Lymph node metastases
A
B
C
D
1. Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA: a cancer journal for clinicians 2005, 55(2):74-108.
2. Bertuccio P, Chatenoud L, Levi F, Praud D, Ferlay J, Negri E, Malvezzi M, La Vecchia C: Recent patterns in gastric cancer: a global overview. International journal of cancer Journal international du cancer 2009, 125(3):666-673.
Primary tumour
3. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. International journal of cancer Journal international du cancer 2010, 127(12):2893-2917.
IHC 0-2
IHC 3
IHC 0-2
65 (94.2)
0 (0.0)
IHC 3
4 (5.8)
9 (100.0)
Total
69
9
Lymph node metastases
4. Lauwers GY: Epithelial Neoplasms of the Stomach. In: Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas: Expert Consult - Online and
Print. Volume 1, 2d edn. Edited by Odze RD, Goldblum JR. Philadelphia: Saunders Elsevier; 2009: 563-580.
5. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T et al: Trastuzumab in combination with
chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase
3, open-label, randomised controlled trial. Lancet 2010, 376(9742):687-697.
Example immunohistochemistry images of (A) a HER2 non-overexpressing primary tumour, (B) adjacent block with a small focus of HER2
overexpressing cells 2x, (C) 10x, and (D) the matched lymph node metastasis.
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