Abstract
BackgroundEGFR and HER2 overexpression has been reported to play important roles in colorectal cancer (CRC) development and metastasis. Ovarian metastasis is rare yet is one of the most malignant metastases of CRC, but very few studies have focused on its biological features. This study aimed to investigate the expression of EGFR and HER2 in ovarian metastases of CRC and to reveal their clinical significance.MethodsThe expression of HER2 and EGFR in both primary tumours and ovarian metastases was analysed by immunohistochemistry (IHC) in 31 CRC patients with ovarian metastases as well as in the primary tumours of 26 CRC patients with non-ovarian metastases. The overall survival time was calculated with a Kaplan-Meier survival curve and compared with a log-rank test.ResultsHER2 positivity in primary tumours was significantly higher in patients with ovarian metastases than in those with non-ovarian metastases (54.5% vs. 36.4%, P < 0.05). The EGFR-positive rate in primary lesions was not significantly different between patients with ovarian metastases and those with non-ovarian metastases (63.6% vs. 58.3%, P > 0.05). HER2 expression was not correlated with age, primary tumour site, tumour differentiation, tumour diameter or vascular cancer embolus (P > 0.05). The positive rates of HER2 and EGFR in ovarian metastases were 44.8 and 69.0%, respectively. HER2 expression in ovarian metastases was correlated with peritoneal metastasis and bilateral ovarian metastasis (P < 0.05) but not with age, synchronous or metachronous ovarian metastases and the primary tumour site (P > 0.05). There was no significant correlation between EGFR expression and the clinicopathological features in ovarian metastases (P > 0.05). CRC patients with HER2-positive ovarian metastases showed a shortened overall survival time compared to that of CRC patients with HER2-negative metastases (17.0 ± 5.2 vs. 32.0 ± 8.3 months).ConclusionOur studies revealed that EGFR and HER2 are highly expressed in the primary tumours and metastases of CRC patients with ovarian metastases. HER2 positivity may be a negative prognostic predictor in patients with ovarian metastases.
Highlights
Epidermal growth factor receptor (EGFR) and HER2 overexpression has been reported to play important roles in colorectal cancer (CRC) development and metastasis
The human epidermal growth factor receptor family consists of four members: EGFR (HER1, erbB1), HER2, HER3 and HER4, all of which regulate the proliferation and differentiation of various tumour cells [7]
The inclusion criteria for the controls were (1) female patients with primary colorectal tumours confirmed by postoperative histopathology; (2) no ovarian metastases detected by computed tomography; and (3) previous confirmation of the HER2 or EGFR expression status with immunohistochemistry (IHC)
Summary
EGFR and HER2 overexpression has been reported to play important roles in colorectal cancer (CRC) development and metastasis. This study aimed to investigate the expression of EGFR and HER2 in ovarian metastases of CRC and to reveal their clinical significance. The diagnosis and treatment of CRC has made great progress in recent years, the 5-year survival rate of patients can reach 90.3%, but the survival rate declines to 70.4 and 12.5% for patients diagnosed with regional and metastatic disease, respectively [2]. The overall median survival time of ovarian metastases reported is only 13.6 months [6]; understanding the mechanism of ovarian metastasis of CRC is of great significance for the prevention and treatment of ovarian metastases. EGFR is positively expressed in 59 to 85% of CRC specimens, and its overexpression is closely related to clinical stage, lymph node metastasis, disease-free survival, poor overall survival, and 5-year recurrence rate [8,9,10]. The positive expression rate of HER2 protein in CRC tumours varied from 2 to 11%, and this rate increased in more advanced diseases [12]
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