BACKGROUND
Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. While the role of HER2 as a prognostic biomarker in colorectal adenocarcinomas (CRCs) remains uncertain, its relevance as a therapeutic target has been established. We undertook the present study to evaluate the frequency of HER2 expression in CRC and to correlate it with various clinicopathological variables.
AIM
To correlate HER2 protein expression and
HER2
gene amplification with clinicopathological features and survival in surgically resected CRC.
METHODS
About 1195 consecutive surgically resected CRCs were analyzed by immunohistochemical staining (IHC) to assess HER2 protein expression, and 141 selected tumors were further evaluated by fluorescence
in situ
hybridization (FISH) to assess
HER2
gene amplification. Follow-up information was available for 1058 patients, and using this information we investigated the prevalence of HER2 protein overexpression and gene amplification in a large series of surgically resected CRCs, and evaluated the relationship between overexpression and clinicopathological parameters and prognosis.
RESULTS
HER2 IHC scores of 3+, 2+, 1+, and 0 were seen in 31 (2.6%), 105 (8.8%), 475 (39.7%), and 584 (48.9%) tumors, respectively.
HER2
gene amplification was seen in 24/29 tumors with an IHC score of 3+ (82.8%; unreadable in 2/31), 12/102 tumors with an IHC score of 2+ (11.8%; unreadable in 2/104), and 0 tumors with IHC score of 1+ (0/10).
HER2
gene amplification was seen in 36/1191 tumors (3.0%; unreadable in 4/1195). Among the tumors with HER2 IHC scores of 3+ and 2+, the mean percentage of tumor cells with positive IHC staining was 90% (median 100%, range 40%-100%) and 67% (median 75%, range 5%-95%), respectively (
P
< 0.05). Among tumors with IHC scores of 2+, those with
HER2
gene amplification had a higher number of tumors cells with positive IHC staining (
n
= 12, mean 93%, median 95%, range 90%-95%) than those without (
n
= 90, mean 70%, median 50%, range 5%-95%) (
P
< 0.05).
HER2
gene status was significantly associated with distant tumor metastasis and stage (
P
= 0.028 and 0.025). HER2 protein overexpression as measured by IHC or
HER2
gene amplification as measured by FISH was not associated with overall survival (OS) or disease-specific survival for the overall group of 1058 patients. However, further stratification revealed that among patients with tubular adenocarcinomas who were 65 years old or younger (
n
= 601), those exhibiting
HER...