Retinoblastoma protein and proliferating-cell nuclear antigen expression as predictors of recurrence in well-differentiated papillary thyroid carcinoma.

PURPOSE: We analyzed retinoblastoma protein (pRB) and proliferating-cell nuclear antigen (PCNA) expression in primary tumors and recurrent lesions of well-differentiated papillary thyroid carcinoma (PTC) to clarify the relationship between their expression and recurrent disease. PATIENTS AND METHODS: The study included 93 patients with PTC. No recurrent disease had developed in 60 patients within 10 years after surgery (group N). Thirty patients in whom recurrent disease had developed after surgery were enrolled in group R. Levels of pRB and PCNA expression were quantified using the CAS 200 system (Cell Analysis Systems, Elmhurst, IL) following immunohistochemical staining. RESULTS: Mean pRB expression level in the primary tumors in group R was significantly lower than that in group N (P < .0001). pRB expression in the tumors with a diameter up to 20 mm was significantly lower than that in tumors larger than 20 mm in group R (P < .01). There were no significant differences in the levels of expression of PCNA in the primary tumors between group N and group R. Univariate analysis demonstrated that the disease-free survival was significantly correlated with pN category, pRB, and PCNA expression level. The subgroup with high-level expression of pRB (> 25%) showed significantly long disease-free survival (P < .001). Furthermore, the subgroup with low-level expression of PCNA (< 35%) showed significantly longer disease-free survival (P < .05). Multivariate analysis showed pRB expression and pN category to be independent prognostic factors for disease-free survival in PTC. CONCLUSION: pRB expression level can be used as a reliable predictor for recurrence of PTC.

The number of 5-fluoro-2'-deoxyuridine-5'-monophosphate binding sites and reduced folate pool in human colorectal carcinoma tissues: changes after tegafur and uracil treatment.

Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil and is inhibited by 5-fluoro-dUMP (FdUMP) to form an inactive ternary complex. We investigated the changes in the number of FdUMP binding sites in human colorectal carcinoma tissues after treatment with 5-fluorouracil derivatives and also examined the mechanisms underlying these changes. The number of FdUMP binding sites was significantly increased in patients who received tegafur and uracil preoperatively [UFT (+) group, n = 14] compared with those who did not [UFT (-) group, n = 36; P < 0.0001]. No amplification of the TS gene was observed in the carcinoma tissues in either group. The level of TS mRNA in the carcinoma tissues showed no significant difference between UFT (-) and UFT (+) groups. There was a significant correlation between the level of TS mRNA and TS in the UFT (-) group, as shown by simple linear regression analysis (P < 0.05). In the UFT (+) group, 9 of 12 cases showed TSf corresponding to their level of TS mRNA. It seemed that the augmentation of TStot is the result of accumulation of ternary complex. Thus, TS inhibition by FdUMP will be insufficient in the absence of methylenetetrahydrofolate in the cytosol, because translation of TS from TS mRNA has been shown to continue in the presence of FdUMP.