Evaluation of Appropriateness of Radical Cystectomy Using p53 and nm23-H1 Protein Expression in Grade III, Muscle Invasive Transitional Cell Carcinoma of Bladder

Park, Dong Soo; Lee, Jin Moo; Yang, Seung Choul

Abstract

OBJECTIVE
About 50% of patients undergoing radical cystectomy for muscle invasive bladder cancer have occult distant micrometastasis. Most of these patients have clinical manifestations of distant metastasis within 1 year of operation, and not likely to achieve 2-year survival. But in other words, the remaining half of patients can expect definite survival benefit from radical surgery. Therefore if those who have micrometastasis can be selected preoperatively, unnecessary cystectomies can be avoided, and bladder preservation by anticancer chemotherapy, radiotherapy, and partial cystectomy can be employedinstead.
MATERIALS AND METHODS
From 1985 to 1993, 45 patients diagnosed with high grade muscle invasive transitional cell carcinoma at transurethral resection of bladder (TURB) who later confirmed to have stage T2, T3a, and T3b rumors after radical cystectomy were selected. Patients with double primary tumor, early death, follow up period under 2 years, and poor quality of paraffinized tissue presentation were excluded.Immunostaining of tumor suppressor gene p53 (DO7 and PAb1801; both wild and mutant type) and antimetastatic gene nm23-H1(NM301) were performed and the survival function was analysed. Stainings were interpreted as positive when more than heterogenous pattern for p53, and stronger than moderately stained for nm23-H1 were seen.
RESULTS
Pathological nodal status (pN stage), combination of p53 and nm23-Hl expression, and p53 expression were correlated with survival. Pathological rumor stage (pT stage), nm23-H1 expression alone were not correlated with survival. Expression of p53 was 44.4% (20/45) and nm23-H1 expression was seen in 55.6% (25/45). Combinations of p53 negative plus nm23-H1 negative, p53 negative plus nm23-H1 positive, p53 positive plus nm23-H1 negative, and p53 positive plus nm23-H1 positive were 12, 13, 8, and 12 cases, respectively. Cases when both proteins were expressed poor survival was observed. Detection time elapsed from cystectomy to metastasis and duration from detection of metastasis to death was only related with N stage.
CONCLUSION
1. When cellular grade of TURB specimen is III, muscle invasive, and positive for both p53 and nm23-H1, the chance of surgical cure by radical cystectomy is significantly reduced. 2. In high grade tumors, the degree of muscle invasion does not affect survival, but might affect the detection time elapsed from cystectomy to metastasis and the duration from detection of metastasis to death. 3. Lymph node metastasis is related to survival, and especially p53 expression is related to survival.