Prognostic implications ofFGFR1andMYCstatus in esophageal squamous cell carcinoma

Abstract

AIMTo investigate the clinicopathological features and prognostic implications of combined MYC and fibroblast growth factor receptor 1 (FGFR1) status in esophageal squamous cell carcinomas (ESCCs).METHODSAll patients with ESCC (n = 180) underwent surgical resection at Seoul National University Hospital sometime between 2000 and 2013. A tissue microarray was constructed using cores obtained from representative tumor areas of formalin-fixed, paraffin-embedded tissue blocks. FGFR1 and MYC copy numbers were quantified using fluorescence in situ hybridization. The level of MYC expression was determined using immunohistochemistry. FGFR1 and MYC amplification status was compared between primary and metastatic lymph nodes. Univariate and multivariate survival analyses were performed according to adjuvant therapy status.RESULTSFGFR1 and MYC amplifications were observed in 21.4% (37/173) and 54.2% (91/168) of patients, respectively, while MYC expression was observed in 58.9% (106/180) of patients. There was a positive correlation between MYC amplification and overexpression (P = 0.002). Although FGFR1 amplification was not associated with MYC amplification or expression, 12.3% (20/163) of patients exhibited both FGFR1 amplification and MYC expression. There was also a correlation in FGFR1 amplification status between matched primary tumors and metastatic lymph nodes (P < 0.001). MYC expression was higher in ESCCs with pT1 (P < 0.001) and in those with no lymph node metastasis (P = 0.023). MYC expression was associated with prolonged disease-free survival (P = 0.036) and overall survival (OS) (P = 0.017) but was not an independent prognostic factor. FGFR1 amplification was an independent predictor for prolonged OS in all patients (P = 0.029) and in those who did not receive adjuvant therapy (P = 0.013). Combined FGFR1 amplification and MYC expression predicted better OS in patients who did not receive adjuvant therapy (P = 0.034) but not in those who did receive adjuvant therapy.CONCLUSIONFGFR1 amplification and MYC expression have prognostic implications in resected ESCCs with respect to adjuvant therapy. The role of FGFR1-targeted therapy in ESCC remains to be explored.

Association of fibroblast growth factor receptor 1 gene amplification with poor survival in patients with esophageal squamous cell carcinoma

“…Unlike EGFR mutation in lung cancer, which is more prevalent in Asians than in Caucasians, the frequency of FGFR1 amplification in ESCC does not seem to be widely different by ethnicity. The frequency of FGFR1 amplification, as detected by FISH analysis in our cohort, was 12.1%, which was higher than 9.4% reported by Loga et al for a Caucasian ESCC patients cohort, [ 13 ] but lower than 21.4% for a small Korean cohort reported by Kwon et al [ 14 ].…”

“…However, they failed to demonstrate an association between FGFR1 amplification and clinical outcome. Kwon et al studied 180 patients with resected ESCC and found FGFR1 amplification in 21.4% (37/173) patients; they observed that FGFR1 amplification was an independent predictor of prolonged OS in these patients [ 14 ]. Kim et al investigated 526 curatively resected ESCC using FISH for FGFR1 amplification and found that an association between high FGFR1 amplification (defined as an FGFR1 /centromer 8 ratio ≥ 2.0, or average number of FGFR1 signals/tumor cell nucleus ≥ 6.0, or percentage of tumor cells containing ≥ 15 FGFR1 signals or large cluster in ≥ 10% with significantly shorter disease-free survival (DFS) and OS [ 15 ].…”

C-terminal binding protein‑2 mediates cisplatin chemoresistance in esophageal cancer cells via the inhibition of apoptosis

“…Understanding of the biology and molecular mechanisms underlying ESCC development and progression is required for advances in the treatment of ESCC (34). Chemotherapy is one of the main therapeutic strategies for the treatment of ESCC (35,36). However, chemoresistance to anticancer drugs greatly reduces the effectiveness of these drugs, and is a huge obstacle to the discovery of a successful therapy for ESCC (37).…”

Blocking FGFR4 exerts distinct anti‐tumorigenic effects in esophageal squamous cell carcinoma

“…However, previous studies on ESCC have focused on other members of the FGFR family, such as FGFR1, FGFR2, and FGFR3 . Few studies have investigated whether FGFR4 protein expression is involved in pathogenesis and progression in ESCC.…”

“…[14][15][16][17][18] However, previous studies on ESCC have focused on other members of the FGFR family, such as FGFR1, FGFR2, and FGFR3. [19][20][21] Few studies have investigated whether FGFR4 protein expression is involved in pathogenesis and progression in ESCC. In this study, we selected a covalent inhibitor, H3B-6527, which targets the unique hinge cysteine in the FGFR4 kinase domain that specifically inhibits FGFR4, and largely spares other FGFRs to play a blocking role.…”