The predictive value of molecular markers (p53, EGFR, ATM, CHK2) in multimodally treated squamous cell carcinoma of the oesophagus

Abstract

Pretherapeutic identification of oesophageal squamous cell carcinomas that will respond to neoadjuvant chemoradiotherapy is an important attempt for improvement of patient's prognosis. In the current study, pretherapeutic biopsies from 94 oesophageal squamous cell carcinomas (cT3, cN0/ þ , cM0) in patients who underwent neoadjuvant chemoradiotherapy (RCTx: 45 Gy plus cisplatin and 5-fluorouracil) and subsequent oesophagectomy in the setting of a single-centre prospective treatment trial were investigated by means of immunohistochemistry. Expression of proteins involved in DNA repair and/or cell-cycle regulation, that is p53, p53 (phosphorylated at Ser15), EGFR, ATM protein kinase (phosphorylated at Ser1981) and checkpoint kinase 2 (CHK2) (phosphorylated at Thr68) was correlated with the response to RCTx and with overall survival. Tumours that were positive for CHK2 expression more frequently showed clinically determined regression after RCTx (69.4%) than tumours that were negative for CHK2 expression (32.1%; P ¼ 0.0011), whereas other parameters did not correlate with tumour regression. Expression of ATM correlated with expression of CHK2 (P ¼ 0.0061) and p53-phospho (P ¼ 0.0064). Expression of p53 correlated with expression of p53-phospho (Po0.0001). In contrast to clinical and histopathological response evaluation, none of the molecular parameters under investigation correlated with overall survival. In conclusion, expression analysis of p53, EGFR CHK2 and ATM has no predictive value in multimodally treated oesophageal squamous cell carcinoma.

p53 is an independent prognostic factor in operable esophageal squamous cell carcinoma: a large-scale study with a long follow-up

“…Thus, assessment of the overexpression and accumulation of mutant p53 protein by immunohistochemistry has been widely used to detect abnormal p53 expression in cancers. Although several studies have examined the relationship between p53 IHC expression and prognosis in ESCC, this work is limited by the small sample size, and the results are controversial [7][8][9][10][16][17][18][19][20][21][22]. We conducted a large-scale study with a long follow-up to examine p53 expression in relation to the clinicopathologic features and prognosis of ESCC.…”

DNA Damage Response-Related Proteins in Gastric Cancer: ATM, Chk2 and p53 Expression and Their Prognostic Value

“…In ovarian cancer, although ATM and Chk2 protein expressions were not found to be individually related to overall survival, at least one alteration was found to be a negative predictor of overall survival [19]. On the other hand, the expressions of ATM and Chk2 were not found to have predictive value in multimodality-treated esophageal squamous cell carcinoma [20]. With regard to gastric cancer, it has been reported that the presence of a low level of phosphorylated ATM is significantly correlated with poor differentiation, lymph node metastasis, and poor 5-year survival [21].…”

Hsp90 is expressed and represents a therapeutic target in human oesophageal cancer using the inhibitor 17-allylamino-17-demethoxygeldanamycin

“…Epidermal growth factor receptor is often overexpressed in patients with oesophageal cancer, suggesting an important role for it in the development of this disease (Sarbia et al, 2007;Wang et al, 2007;Wei et al, 2007). All Kyse cell lines were found to express EGFRs, whereas HER2 was expressed only in Kyse410 (data not shown).…”