Immunostaining of thymidylate synthase and p53 for predicting chemoresistance to S-1/cisplatin in gastric cancer

Abstract

High expression of thymidylate synthase (TS) and inactivation of p53 are allegedly associated with chemoresistance. The authors evaluated TS and p53 expression in gastric cancer treated with neoadjuvant S-1/cisplatin chemotherapy. Paraffin sections of pretreatment biopsy and surgical specimens from 41 gastric cancers were immunostained for TS and p53 protein after appropriate antigen retrieval. Fifty-one cases without neoadjuvant chemotherapy were also studied. In the pretreatment biopsies, high expression of TS was seen in 8% of the histologic responders, in 28% of the nonresponders and in 31% of the controls. High expression of p53 was observed in 56% of the nonresponders, but in 8% of the responders and in 29% of the controls (Po0.01 and Po0.05, respectively). The TS-and/or p53-high phenotype was seen in 76% of the nonresponders and in 54% of the controls, but in 8% of the responders (Po0.0001 and Po0.005, respectively). The data of the surgical specimens were consistent with those of the pretreatment biopsies. These results suggest that immunostaining for TS and p53 protein is useful for pretreatment selection of gastric cancer patients unresponsive to S-1/cisplatin chemotherapy.

Tumour regression and ERCC1 nuclear protein expression predict clinical outcome in patients with gastro-oesophageal cancer treated with neoadjuvant chemotherapy

“…Nuclear p53 correlated with disease-specific (P ¼ 0.028) and overall survival (Po0.001) in the primary surgery group but no significant associations were observed in the neoadjuvant group. This is in contrast to a study by Kamoshida et al (2007), who showed that p53 expression was correlated with resistance to chemotherapy in gastric cancer patients.…”

“…p53 is a transcription factor that binds to specific sites in the regulatory regions of p53-responsive genes, leading to cellular events such as growth arrest (perhaps to allow for DNA repair), or where there is extensive DNA damage to initiate apoptosis. p53 expression is common in gastro-oesophageal cancer and may influence response to chemotherapy (Kamoshida et al, 2007).…”

Neuro-regulation of lower esophageal sphincter Predictive value of Ki67 and p53 in locally advanced rectal cancer: Correlation with thymidylate synthase and histopathological tumor regression after neoadjuvant 5-FU-based chemoradiotherapy

“…There are only very rare data of p53 and TS in the neoadjuvant setting. Kamoshida et al demonstrated in gastric cancer neoadjuvantly treated with S-1/cisplatin chemotherapy that high expression of TS and/or p53 in the pre-treatment biopsies predicted chemoresistance [40] . Other investig ators [41] were not able to find any cor relation between p53 and either TS or tumor regression.…”

Levels and expressions of orotate phosphoribosyltransferase in gastric carcinoma and normal gastric mucosa tissues

“…The analysis showed that postoperative adjuvant chemotherapy with S-1 alone significantly improved postoperative survival in patients with stage II/III gastric cancer who had undergone D2 gastrectomy. Although the overall anticancer effect was signifi cant, anticancer effects in individual cases were not uniform, and a certain number of patients showed chemoresistance to S-1-based chemotherapy [18]. Thus, a novel factor that can predict response to S-1-based chemotherapy is needed.…”