Conway Gee

Combined Effects of p53, p21, and pRb Expression in the Progression of Bladder Transitional Cell Carcinoma

PURPOSE To determine the combined effects of p53, p21, and pRb alterations in predicting the progression of bladder transitional cell carcinoma. PATIENTS AND METHODS p53, p21, and pRb expression was examined immunohistochemically on archival radical cystectomy samples from 164 patients with invasive or high-grade recurrent superficial transitional cell carcinoma (TCC; lymph node-negative, 117 patients; lymph node-positive, 47 patients). Median follow-up was 8.6 years. Based on percentage of nuclear reactivity, p53 was considered as wild-type (0% to 10%) or altered (>10%); p21 was scored as wild-type (>10%) or altered (<10%); and pRb status was considered wild-type (1% to 50%) or altered (0% or >50%). RESULTS As individual determinants, the p53, p21, and pRb status were independent predictors of time to recurrence (P<.001, P<.001, and P<.001, respectively), and overall survival (P<.001, P=.002, and P=.001, respectively). By examining these determinants in combination, patients were categorized as group I (no alteration in any determinant, 47 patients), group II (any one determinant altered, 51 patients), group III (any two determinants altered, 42 patients), and group IV (all three determinants altered, 24 patients). The 5-year recurrence rates in these groups were 23%, 32%, 57%, and 93%, respectively (log-rank P<.001), and the 5-year survival rates were 70%, 58%, 33%, and 8%, respectively (log-rank P<.001). After stratifying by stage, the number of altered proteins remained significantly associated with time to recurrence and overall survival. CONCLUSION This study suggests that alterations in p53, p21, and pRb act in cooperative or synergistic ways to promote bladder cancer progression. Examining these determinants in combination provides additional information above the use of a single determinant alone.

Granulocyte-macrophage-colony-stimulating factor added to a multipeptide vaccine for resected Stage II melanoma.

Forty‐eight patients with resected Stages IIA and IIB melanoma were immunized with two tumor antigen epitope peptides derived from gp100209–217 (210M) (IMDQVPSFV) and tyrosinase368–376 (370D) (YMDGTMSQV) emulsified with incomplete Freunds adjuvant (IFA). Patients were assigned randomly to receive either peptides/IFA alone or with 250 μm of granulocyte‐macrophage–colony‐stimulating factor (GM‐CSF) subcutaneously daily for 5 days to evaluate the toxicities and immune responses in either arm. Time to recurrence and survival were secondary end points.

Variations in treatment of rectal cancer

PURPOSE: Surgical options for the treatment of rectal cancer may involve sphincter-sparing procedures (SSP) or abdominoperineal resection (APR). We sought to examine variations in the surgical treatment of rectal cancer for a large, well-defined patient population and specifically to determine if differences exist in management and survival based on hospital type and surgical caseload. METHODS: The Cancer Surveillance Program database for Los Angeles County was used to retrospectively retrieve data on all patients who underwent SSP or APR for rectal adenocarcinoma between 1988 and 1992. RESULTS: A total of 2,006 patients with adenocarcinoma of the rectum underwent SSP or APR during the study period. Overall, 55 percent underwent SSP, and the remaining 45 percent underwent APR. Use of SSP remained relatively constant for each year of the five-year period. Substantial variability was seen in the use of SSP at various hospital types. For localized disease, this varied from as low as 52 percent at teaching hospitals to as high as 78 percent at hospitals approved by the American College of Surgeons (P=0.067). To examine the role of caseload experience, hospitals were divided into those completing an average of five or fewer rectal cancer cases per yearvs.those completing an average of more than five cases per year. For localized disease, hospitals with higher caseloads performed SSP in significantly more cases, 69vs.63 percent (P=0.049). Survival was seen to be significantly improved for patients operated on at hospitals with higher caseloads, in cases of both localized and regional diseases (P<0.001). CONCLUSION: Surgical choices in the treatment of rectal cancer may vary widely, even in a well-defined geographic region. Although the reasons for this variability are multifactorial, hospital environment and surgical caseload experience seem to have a significant role in the choice of surgical procedure and on survival.

Survival analysis after resection of metastatic disease followed by peptide vaccines in patients with Stage IV melanoma

Metastatic melanoma carries a poor prognosis, with a median survival of 7–9 months. Surgical resection of metastatic disease has been advocated to improve survival. Immunotherapy after metastasectomy may further improve the outcome for high‐risk resected disease.

Segregation and linkage analysis for longitudinal measurements of a quantitative trait

We present a method for using slopes and intercepts from a linear regression of a quantitative trait as outcomes in segregation and linkage analyses. We apply the method to the analysis of longitudinal systolic blood pressure (SBP) data from the Framingham Heart Study. A first-stage linear model was fit to each subjects SBP measurements to estimate both their slope over time and an intercept, the latter scaled to represent the mean SBP at the average observed age (53.7 years). The subject-specific intercepts and slopes were then analyzed using segregation and linkage analysis. We describe a method for using the standard errors of the first-stage intercepts and slopes as weights in the genetic analyses. For the intercepts, we found significant evidence of a Mendelian gene in segregation analysis and suggestive linkage results (with LOD scores ≥ 1.5) for specific markers on chromosomes 1, 3, 5, 9, 10, and 17. For the slopes, however, the data did not support a Mendelian model, and thus no formal linkage analyses were conducted.