Clinical significance of HER2 and EGFR expression in colorectal cancer patients with ovarian metastasis
Tóm tắt
EGFR 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. The 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. HER2 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). Our 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.
Tài liệu tham khảo
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018.
Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin. 2014;64(2):104–17.
Si Y, Lee J-I, Kim S-H, Kim J-H, Kim HJ, Lee YS, Cho HM, Kim JG, Oh ST, Lee IK. Clinicopathological characteristics of ovarian metastasis from colorectal Cancer. Journal of the Korean Surgical Society. 2010;79(4):287.
Wenhua Li 1 HW, Jian Wang 3 , Fangfang LV 1 , Xiaodong Zhu 1 and Zhonghua Wang 1,4*: ovarian metastases resection from extragenital primary sites: outcome and prognostic factor analysis of 147 patients. BMC Cancer 2012, 12:278 2012.
Lee SJ, Lee J, Lim HY, Kang WK, Choi CH, Lee JW, Kim TJ, Kim BG, Bae DS, Cho YB, et al. Survival benefit from ovarian metastatectomy in colorectal cancer patients with ovarian metastasis: a retrospective analysis. Cancer Chemother Pharmacol. 2010;66(2):229–35.
Qiang Feng WP, Zhao-Xu Zheng, Jian-Jun Bi, Xing-Hua Yuan: Clinicopathologic characteristics and prognostic factors of 63 gastric cancer patients with metachronous ovarian metastasis. Cancer Biol Med 2013;10:86–91 2013.
a1 OMNRLHe: The ErbB signaling network:receptor heterodimerization in development and cancer EMBO J,2000,19(13):3159—3167. 2000.
Rego RL, Foster NR, Smyrk TC, Le M, O'Connell MJ, Sargent DJ, Windschitl H, Sinicrope FA. Prognostic effect of activated EGFR expression in human colon carcinomas: comparison with EGFR status. Br J Cancer. 2010;102(1):165–72.
Lee W-S, Jeong Heum B, Jung Nam L, Woon Kee L: Mutations in K-ras and epidermal growth factor receptor expression in Korean patients with stages III and IV colorectal Cancer. Int J Surg Pathol 2011, 19(2):145–151.
Cappuzzo F, Finocchiaro G, Rossi E, Janne PA, Carnaghi C, Calandri C, Bencardino K, Ligorio C, Ciardiello F, Pressiani T, et al. EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients. Ann Oncol. 2007;19(4):717–23.
Sawada K, Nakamura Y, Yamanaka T, Kuboki Y, Yamaguchi D, Yuki S, Yoshino T, Komatsu Y, Sakamoto N, Okamoto W, et al. Prognostic and predictive value of HER2 amplification in patients with metastatic colorectal Cancer. Clin Colorectal Cancer. 2018;17(3):198–205.
Siena S, Sartore-Bianchi A, Marsoni S, Hurwitz HI, McCall SJ, Penault-Llorca F, Srock S, Bardelli A, Trusolino L: Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer. Annals of oncology : official journal of the European Society for Medical Oncology 2018, 29(5):1108–1119.
Ruschoff J, Hanna W, Bilous M, Hofmann M, Osamura RY, Penault-Llorca F, van de Vijver M, Viale G. HER2 testing in gastric cancer: a practical approach. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2012;25(5):637–50.
Richman SD, Southward K, Chambers P, Cross D, Barrett J, Hemmings G, Taylor M, Wood H, Hutchins G, Foster JM, et al. HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials. J Pathol. 2016;238(4):562–70.
Ingold Heppner B, Behrens HM, Balschun K, Haag J, Kruger S, Becker T, Rocken C. HER2/neu testing in primary colorectal carcinoma. Br J Cancer. 2014;111(10):1977–84.
Valtorta E, Martino C, Sartore-Bianchi A, Penaullt-Llorca F, Viale G, Risio M, Rugge M, Grigioni W, Bencardino K, Lonardi S, et al. Assessment of a HER2 scoring system for colorectal cancer: results from a validation study. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2015;28(11):1481–91.
Shan L, Lv Y, Bai B, Huang X, Zhu H. Variability in HER2 expression between primary colorectal cancer and corresponding metastases. J Cancer Res Clin Oncol. 2018.
Missiaglia E, Jacobs B, D'Ario G, Di Narzo AF, Soneson C, Budinska E, Popovici V, Vecchione L, Gerster S, Yan P et al: Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Annals of oncology : official journal of the European Society for Medical Oncology 2014, 25(10):1995–2001.
Nam SK, Yun S, Koh J, Kwak Y, Seo AN, Park KU, Kim DW, Kang SB, Kim WH, Lee HS. BRAF, PIK3CA, and HER2 oncogenic alterations according to KRAS mutation status in advanced colorectal cancers with distant metastasis. PLoS One. 2016;11(3):e0151865.
Osako T, Miyahara M, Uchino S, Inomata M, Kitano S, Kobayashi M. Immunohistochemical study of c-erbB-2 protein in colorectal cancer and the correlation with patient survival. Oncology. 1998;55(6):548–55.
Kapitanovic S, Radosevic S, Kapitanovic M, Andelinovic S, Ferencic Z, Tavassoli M, Primorac D, Sonicki Z, Spaventi S, Pavelic K, et al. The expression of p185(HER-2/neu) correlates with the stage of disease and survival in colorectal cancer. Gastroenterology. 1997;112(4):1103–13.
Kruszewski WJ, Rzepko R, Ciesielski M, Szefel J, Zielinski J, Szajewski M, Jasinski W, Kawecki K, Wojtacki J. Expression of HER2 in colorectal cancer does not correlate with prognosis. Dis Markers. 2010;29(5):207–12.
Martin V, Landi L, Molinari F, Fountzilas G, Geva R, Riva A, Saletti P, De Dosso S, Spitale A, Tejpar S, et al. HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients. Br J Cancer. 2013;108(3):668–75.
Metges J, Gamelin E, Volant A, Capitain O, Ramee J, Raoul J, Douillard J, Etienne P, Cumin I, Dupuis O: EGFR expression is unreliable to decide for Cetuximab treatment in patients with metastatic colorectal Cancer: results from “ERBITUX-OUEST”. Open Journal of Internal Medicine 2016, 06(02):56–67.
Bibeau F, Boissiere-Michot F, Sabourin JC, Gourgou-Bourgade S, Radal M, Penault-Llorca F, Rochaix P, Arnould L, Bralet MP, Azria D, et al. Assessment of epidermal growth factor receptor (EGFR) expression in primary colorectal carcinomas and their related metastases on tissue sections and tissue microarray. Virchows Archiv : an international journal of pathology. 2006;449(3):281–7.