Structural alteration of p53 protein in patients with muscle invasive bladder transitional cell carcinoma.

PURPOSE: Recent data imply that 3-dimensional (D) p53 protein modeling provides more specific information on its function in patients with pancreatic adenocarcinoma. In addition to immunohistochemical and single strand conformational polymorphism analysis, we performed 3-D p53 protein modeling and correlated our results with the disease-free survival of patients with muscle invasive transitional cell carcinoma of the bladder who underwent surgery. MATERIALS AND METHODS: We identified 43 patients and analyzed p53 status in each by immunohistochemical testing, single strand conformational polymorphism and DNA sequencing with 3-D protein modeling. Median followup was 38 months (range 4 to 92). The results of each analysis were compared and correlated with cancer specific survival. Statistical analysis was performed using the log rank test on Kaplan-Meier survival curves. RESULTS: The population included 30 men and 13 women 35 to 84 years old (median age 65). Nuclear over expression of p53 protein was observed in 26 of the 43 cases (60%). Lymph node involvement did not correlate with p53 over expression. Significantly more patients with lymph node metastasis died of cancer. Median survival in the 26 patients with p53 over expression was 28 months versus 57 in those with negative staining (p = 0.25). Mutation analysis by single strand conformational polymorphism revealed no abnormality in 24 patients (56%) with a median survival of 28 months, whereas we noted abnormal mutational analysis in 19 (44%) with a median survival of 38 months (p = 0.33). Of 19 single strand conformational polymorphism positive cases DNA sequencing showed mutation near the DNA binding site in 10 (53%), mutation away from the site in 6 (32%) and no mutation in 3 (17%). No survival difference was detected in cases with mutation away and near the DNA binding site, respectively (p = 0.69). CONCLUSIONS: In this group of patients treated with radical cystectomy for muscle invasive bladder transitional cell carcinoma, analysis of p53 protein and the p53 gene by immunohistochemical testing, single strand conformational polymorphism and mutational analysis did not correlate with cancer specific survival.

Grading the invasive component of urothelial carcinoma of the bladder and its relationship with progression-free survival.

Although grading is valuable prognostically in pTa and pT1 papillary urothelial carcinoma, it is unclear whether it provides any prognostic information when applied to the invasive component in muscle-invasive carcinoma. The authors analyzed 93 cases of muscle-invasive urothelial carcinoma of the bladder treated with radical cystectomy for which follow-up information was available. Each case was graded using the Malmström grading system for urothelial carcinoma, applied to the invasive component. Pathologic stage, lymph node status, and histologic invasion pattern were also recorded and correlated with progression-free survival. Thirty-four cases (37%) were pT2, 40 (43%) were pT3, and 19 (20%) were pT4. Of the 77 patients who had a lymph node dissection at the time of cystectomy, 34 (44%) had metastatic carcinoma to one or more lymph nodes. The median survival for pT2, pT3, and pT4 stages was 85, 24, and 29 months, respectively (p = 0.0001). Lymph node-negative and lymph node-positive patients had a median survival of 63 and 23 months, respectively (p = 0.0001). Fifteen patients (16%) were graded as 2b and 78 patients (84%) were graded as 3. Median survival of patients graded as 2b was 34 months compared with 31 months for patients graded as 3 (p value not significant). Three invasive patterns were recognized: nodular (n = 13, 14%), trabecular (n = 39, 42%), and infiltrative (n = 41, 44%). The presence of any infiltrative pattern in the tumor was associated with a median survival of 29 months, compared with 85 months in tumors without an infiltrative pattern (p = 0.06). Pathologic T stage and lymph node status remain the most powerful predictors of progression in muscle-invasive urothelial carcinoma. In this group of patients histologic grade, as defined by the Malmström system and as applied to the invasive component, provided no additional prognostic information. An infiltrative growth pattern may be associated with a more dismal prognosis.

Lymph node size does not correlate with the presence of prostate cancer metastasis.

OBJECTIVES: To determine whether lymph node size is a surrogate marker for lymph node metastasis. METHODS: We reviewed 980 patients who underwent radical retropubic prostatectomy with bilateral pelvic lymph node dissection for clinically localized prostate cancer, of whom 63 had lymph node metastases. A comparable group of patients with prostate cancer undergoing radical prostatectomy who did not have lymph node involvement was identified using the following parameters: serum prostate-specific antigen level, clinical and pathologic stage, and pre- and postoperative Gleason score. The axial and longitudinal dimensions of the nodes from patients with and without metastases were analyzed to assess the significance of lymph node size in predicting the presence of metastases. All patients had negative preoperative computed tomography (CT) and bone scans. Of the 63 patients with lymph node metastases, 48 had tissue available for measuring the dimensions of the lymph nodes. RESULTS: A total of 76 metastatic and 92 negative lymph nodes were identified from the patients with and without metastatic nodes, respectively. The mean nodal longitudinal size was 1.65 cm (range 0.2 to 6.5) and 3.50 cm (range 0.5 to 9) for positive and negative nodes, respectively (P = 0.0001). The mean axial nodal size was 0.8 cm (range 0.2 to 3.2) and 1.0 cm (range 0.2 to 2.2) for positive and negative lymph nodes, respectively. In 56 metastatic nodes (74%), the axial size was less than 1 cm and in 20 (26%) less than 5 mm. CONCLUSIONS: Lymph node size should not be used as a surrogate for the presence of lymph node metastases. Although no patient had enlarged lymph nodes by CT scan criteria (greater than 1.5 cm), 6 (8%) of 48 and 19 (12%) of 48 patients with and without lymph node metastases, respectively, had nodes with an axial dimension greater than 1.5 cm.

Population-based study of pelvic lymph node positivity in clinically localized prostate cancer: a study comparing African Americans and whites.

OBJECTIVES: To evaluate the correlation between race and lymph node metastasis for prostate cancer by analyzing which preoperative parameters may predict lymph node status in both races. METHODS: We analyzed a group of patients (552 American white men [AWM] and 423 African-American men [AAM]) who underwent radical prostatectomy plus modified pelvic lymphadenectomy between January 1991 and June 1997. Patients who received neoadjuvant radiation or hormone therapy were excluded. Univariate and multivariate analyses were performed to determine the influence of race on lymph node positivity, as well as to correlate the preoperative parameters (serum prostate-specific antigen [PSA], biopsy Gleason score, and clinical stage) with lymph node metastasis for each race separately. RESULTS: The AAM presented with significantly higher preoperative Gleason scores and PSA levels than AWM. However, comparing lymph node status by race, the difference of positivity (41 AWM [7.4% and 22 AAM [5.2%]) was not statistically significant (P = 0.16). The percentage of positive nodes was similar in both races for each subset of PSA, Gleason score, and clinical stage. Despite the statistical significance of the three preoperative parameters in univariate analysis, in multivariate analysis only PSA and Gleason score were independent predictors of positive lymph nodes. CONCLUSIONS: There is no influence of race on lymph node metastasis, despite AAM presenting with higher preoperative Gleason scores and PSA levels. In multivariate analysis, preoperative Gleason score and PSA were independent factors for positive nodes regardless of race.