Metallothionein Expression Correlates with the Pathological Response of Patients with Esophageal Cancer Undergoing Preoperative Chemoradiation Therapy

Abstract

Immunohistochemical staining for metallothionein (MT) and p53 was performed on biopsy specimens of 30 patients with esophageal squamous cell carcinoma who had received curative resection following preoperative chemoradiation. The pathologic response to chemoradiation was a partial response in 19 cases and no change was observed in 11 cases. In 16 cases with MT-positive tumor, 10 (62.5%) showed no change. In 14 cases with MT-negative tumor, 13 (92.8%) showed partial response. In 8 patients with negative staining for p53 and MT, 7 were responders, whereas in 9 patients with positive staining for p53 and MT, 6 were nonresponders. The pathologic response was significantly associated with the prognosis (p = 0.0167). The survival rate of the responders was significantly better than that of the nonresponders. These findings suggest that MT might be a prognostic marker, and consequently we can select the patients who will benefit from preoperative chemoradiation.

Expression of Metallothionein in Colorectal Cancers and Synchronous Liver Metastases

“…Recently, Ku et al [31]reported that high-dose doxorubicin administered via the hepatic artery to treat multiple advanced hepatocellular carcinoma yielded long-term complete remission in some patients and was effective in the majority of patients. In esophageal squamous cell carcinoma patients, MT expression might be correlated with the patient’s prognosis treated with cisplatin [9, 10]. In patients with MT-negative tumors treated with cisplatin, survival was better than in those with MT-positive tumors [9].…”

“…Overexpression of MT has also been reported to correlate with resistance to anticancer reagents such as cisplatin and alkylating agents [5, 6, 7, 8, 9, 10]. It was considered as an important mechanism during tumor progression and appears to be predominantly correlated with more advanced, highly malignant tumors [11, 12].…”

Bone marrow micrometastases in esophageal carcinoma: a 10-year follow-up study

“…3 Therefore, identification of reliable biological markers at the time of diagnosis and staging, indicating adverse prognosis and potential for metastatic spread, may facilitate selection of patients for chemotherapy as well as identifying those patients that might be best served by proceeding direct to surgery alone. 4,5 The extent of systemic tumor dissemination remains the best predictor of clinical outcome. 6 However, in patients with no demonstrable evidence of overt metastases, subclinical metastatic disease may be present at the time of diagnosis, and evade current staging and imaging techniques.…”

Expression of Metallothionein in Oral Cancer

“…This hypothesis is confirmed by studies conducted on human malignancies (e.g. ovarian cancer, testicular cancer, colorectal cancer, breast cancer and squamocellular oesophageal cancer), showed that insensitivity of the tumours to chemotherapy was related to their MT over-expression (Yamamoto et al, 1999;Vazquez-Ramirez et al, 2000;Dziegiel et al, 2003;Surowiak et al, 2005;Surowiak et al, 2007). In view of the above, some authors include MT, in parallel to multi-drug resistance proteins (MDR), to significant factors responsible for the lack of therapeutic efficacy of some cytostatic agents (Theocharis et al, 2004).…”