Expression of thymidylate synthase in relation to survival and chemosensitivity in gastric cancer patients.

Expression of thymidylate synthase (TS) has been studied as a prognostic factor and mechanism of drug resistance in gastric cancers. The relationship between TS expression in surgically resected specimens and clinicopathological factors was examined in 216 gastric cancer patients. Immunohistochemical demonstration of the protein was achieved using an anti-TS polyclonal antibody. Positive TS staining was observed in 50 patients (23.1%). Lymph node metastasis was more frequent in patients with TS-positive tumors than in those with TS-negative tumors (P<0.01). Patients were followed for more than 5 years and survival was examined. In 163 patients who received fluorouracil (FU)-based chemotherapy, the overall 5-year survival rate was 41.8% for patients with TS-positive tumors and 57.0% for patients with TS-negative tumors (P<0.01). In the 53 patients who did not receive chemotherapy, these figures were 25.6% and 79.5%, respectively (P<0.05). In patients with T3 gastric cancer who were treated with curative gastrectomy, however, FU-based chemotherapy did not affect survival of either patients with TS-positive tumors or with TS-negative tumors. Multivariate analysis also revealed TS expression to be a significant variable for predicting postoperative survival (P<0.05). These results indicate that TS expression can be used as an independent prognostic factor for patients with gastric cancer. However, TS expression is not a major predictor of the efficacy of FU-based chemotherapy.

Tumor response to neoadjuvant chemotherapy correlates with the expression of P-glycoprotein and PCNA but not GST-pi in the tumor cells of cervical carcinoma.

OBJECTIVE: To identify the clinicopathological and chemoresistant factors predicting the response to neoadjuvant chemotherapy and the patient prognosis in high-risk cervical carcinomas. METHODS: We retrospectively reviewed 47 patients with locally advanced or bulky cervical carcinoma treated with two courses of intraarterial infusion of cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil (5-FU), followed by radical hysterectomy at our hospital between 1988 and 1995. Expressions of the chemoresistance-related proteins, such as P-glycoprotein, glutathione S-transferase pi (GST-pi), and proliferating cell nuclear antigen (PCNA) in the tumor cells, were examined by immunohistochemistry using pretreatment biopsy specimens. These results were compared with the chemotherapeutic response, which was evaluated by magnetic resonance imaging (MRI) and histopathology. Outcome of the patients was also studied. RESULTS: Chemotherapeutic effect of either complete (CR) or partial (PR) response on MRI was obtained in 36 of the 47 (86%) patients. Poor response to chemotherapy was significantly correlated with P-glycoprotein expression (P < 0.005) and low PCNA labeling (P < 0. 05), but not GST-pi expression in the tumor cells. Independent prognostic factors for patient survival were parametrial involvement and lymph node metastasis. Neither the expression of GST-pi nor PCNA was correlated with the patient survival. CONCLUSION: Assessment of the expression of P-glycoprotein and PCNA is potentially useful for the prediction of tumor response to neoadjuvant chemotherapy for cervical carcinomas.