Prognostic Significance and Gene Expression Profiles of p53 Mutations in Microsatellite-Stable Stage III Colorectal Adenocarcinomas

Although the prognostic value of p53 abnormalities in Stage III microsatellite stable (MSS) colorectal cancers (CRCs) is known, the gene expression profiles specific to the p53 status in the MSS background are not known. Therefore, the current investigation has focused on identification and validation of the gene expression profiles associated with p53 mutant phenotypes in MSS Stage III CRCs. Genomic DNA extracted from 135 formalin-fixed paraffin-embedded tissues, was analyzed for microsatellite instability (MSI) and p53 mutations. Further, mRNA samples extracted from five p53-mutant and five p53-wild-type MSS-CRC snap-frozen tissues were profiled for differential gene expression by Affymetrix Human Genome U133 Plus 2.0 arrays. Differentially expressed genes were further validated by the high-throughput quantitative nuclease protection assay (qNPA), and confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and by immunohistochemistry (IHC). Survival rates were estimated by Kaplan-Meier and Cox regression analyses. A higher incidence of p53 mutations was found in MSS (58%) than in MSI (30%) phenotypes. Both univariate (log-rank, P = 0.025) and multivariate (hazard ratio, 2.52; 95% confidence interval, 1.25–5.08) analyses have demonstrated that patients with MSS-p53 mutant phenotypes had poor CRC-specific survival when compared to MSS-p53 wild-type phenotypes. Gene expression analyses identified 84 differentially expressed genes. Of 49 down-regulated genes, LPAR6, PDLIM3, and PLAT, and, of 35 up-regulated genes, TRIM29, FUT3, IQGAP3, and SLC6A8 were confirmed by qNPA, qRT-PCR, and IHC platforms. p53 mutations are associated with poor survival of patients with Stage III MSS CRCs and p53-mutant and wild-type phenotypes have distinct gene expression profiles that might be helpful in identifying aggressive subsets

Evaluation of lymph node numbers for adequate staging of Stage II and III colon cancer

<p>Abstract</p> <p>Background</p> <p>Although evaluation of at least 12 lymph nodes (LNs) is recommended as the minimum number of nodes required for accurate staging of colon cancer patients, there is disagreement on what constitutes an adequate identification of such LNs.</p> <p>Methods</p> <p>To evaluate the minimum number of LNs for adequate staging of Stage II and III colon cancer, 490 patients were categorized into groups based on 1-6, 7-11, 12-19, and ≥ 20 LNs collected.</p> <p>Results</p> <p>For patients with Stage II or III disease, examination of 12 LNs was not significantly associated with recurrence or mortality. For Stage II (HR = 0.33; 95% CI, 0.12-0.91), but not for Stage III patients (HR = 1.59; 95% CI, 0.54-4.64), examination of ≥20 LNs was associated with a reduced risk of recurrence within 2 years. However, examination of ≥20 LNs had a 55% (Stage II, HR = 0.45; 95% CI, 0.23-0.87) and a 31% (Stage III, HR = 0.69; 95% CI, 0.38-1.26) decreased risk of mortality, respectively. For each six additional LNs examined from Stage III patients, there was a 19% increased probability of finding a positive LN (parameter estimate = 0.18510, p < 0.0001). For Stage II and III colon cancers, there was improved survival and a decreased risk of recurrence with an increased number of LNs examined, regardless of the cutoff-points. Examination of ≥7 or ≥12 LNs had similar outcomes, but there were significant outcome benefits at the ≥20 cutoff-point only for Stage II patients. For Stage III patients, examination of 6 additional LNs detected one additional positive LN.</p> <p>Conclusions</p> <p>Thus, the 12 LN cut-off point cannot be supported as requisite in determining adequate staging of colon cancer based on current data. However, a minimum of 6 LNs should be examined for adequate staging of Stage II and III colon cancer patients.</p

High Expression of Testes-Specific Protease 50 Is Associated with Poor Prognosis in Colorectal Carcinoma

Testes-specific protease 50 (TSP50) is normally expressed in testes and abnormally expressed in breast cancer, but whether TSP50 is expressed in colorectal carcinoma (CRC) and its clinical significance is unclear. We aimed to detect TSP50 expression in CRC, correlate it with clinicopathological factors, and assess its potential diagnostic and prognostic value. = 0.009).Our data demonstrate that TSP50 is a potential effective indicator of poor survival for CRC patients, especially for those with early-stage tumors

Oncological and functional outcomes following open radical prostatectomy: how patients may achieve the "trifecta"?

PURPOSE: The desirable outcomes after open radical prostatectomy (RP) for localized prostate cancer (PC) are to: a) achieve disease recurrence free, b) urinary continence (UC), and c) maintain sexual potency (SP). These 3 combined desirable outcomes we called it the "Trifecta". Our aim is to assess the likelihood of achieving the Trifecta, and to analyze the influencing the Trifecta . MATERIALS AND METHODS: A total of 1738 men with localized PC underwent RP from 1992-2007 by a single surgeon. The exclusion criteria for this analysis were: preoperative hormonal or radiation therapy, preoperative urinary incontinence or erectile dysfunction, follow-up less than 24 months or insufficient data. Post-operative Trifecta factors were analyzed, including biochemical recurrence (BR).. We defined: BR as PSA > 0.2 ng/mL, urinary continence as wearing no pads, and sexual potency as having erections sufficient for intercourse with or without a phosphodiesterase-5 inhibitor. RESULTS: A total of 831 patients met the inclusion criteria. The mean age of the entire cohort was 59 years old. The median follow-up was 52 months (mean 60, range 24-202). The BR, UC and SP rates were 18.7%, 94.5%, and 71% respectively. Trifecta was achieved in 64% at 2 year follow-up, and 61% at 5 year follow-up. Multivariate analysis revealed age at time of surgery, pathologic Gleason score (PGS), pathologic stage, specimen weight, and nerve sparing (NS) were independent factors. CONCLUSIONS: Age at time of surgery, pathologic GS, pathologic stage, specimen weight and NS were independent predictors to achieve the Trifecta following radical prostatectomy. This information may help patients counseling undergoing radical prostatectomy for localized prostate cancer

Role of Patient-Physician Dialogue in Selecting the Type of Urinary Diversion

Introduction: We analyze patient-physician dialogue prior to radical cystectomy (RC) when choosing the type of urinary diversion (UD). Methods: 132 patients operated by one surgical team between 2003 and 2005 were included. Physician’s recommendation, patient’s decision and UD (neobladder (NB) or ileal conduit (IC)) performed were analyzed. Patients were grouped based on age, considering that age is often a limiting factor for NB. Results: When offered either NB or IC, 85% (49/58) in group I (<70 years) and 55% (12/22) in group II (≧70 years) elected NB. An IC was suggested for 16% (11/69) in group I and 65% (41/63) in group II. Six patients (2 in group I, 4 in group II) wanted a NB even though an IC was suggested. Conclusions: Counseling patients is important. When an IC was suggested, over 80% accepted this advice. When both were offered, younger patients usually elected a NB. Older patients preferred an IC

Tumor thrombus involving the inferior vena cava in renal malignancy: is there a difference in clinical presentation and outcome among right and left side tumors?

PURPOSE: Renal cell carcinoma (RCC) has a propensity to propagate into the renal vein and inferior vena cava (IVC). Due to inherent differences in the venous anatomy of the right and left kidneys, tumor thrombus involvement of IVC may vary. The aim of this study is to compare clinical presentation and outcome of right vs. left RCC with IVC thrombus. MATERIALS AND METHODS: Patients who underwent radical nephrectomy and IVC thrombectomy between 1997 and 2008 were identified. All relevant data were collected and analyzed. Results: Eight-seven patients were included. Sixty patients (69%) had a right sided tumor. Mean tumor size was 10.2 (± 4) cm and was not significantly different on either side. Fifty-six percent of right sided tumors had level-III (intra-hepatic) or higher tumor thrombus, while 22% of left sided tumors had similar level thrombus extension (p < 0.0001). Nearly 50% of left sided tumors showed level-I thrombus compared to 10% of right side tumors. A comparison of age, estimated blood loss and transfusion rate was not significantly different. The recurrence free (p = 0.9) and disease specific survival (p = 0.4) were not significantly different between the right and left side tumors with IVC thrombus. Conclusion: A level-III IVC tumor thrombus is more frequently seen with a right side tumor. However, clinical and operative characteristics among the left and right sided tumors with IVC thrombus were not different. More significantly, recurrence rate and survival did not differ with the laterality of the tumor

Comparison of urologist reimbursement for managing patients with low-risk prostate cancer by active surveillance versus total prostatectomy

Active surveillance (AS) is an alternative to total prostatectomy (TP) in managing low-risk prostate cancer (PC). Our aim is to compare urologist reimbursement for managing low-risk PC by AS or TP. The urologist's reimbursement for TP includes the fee for the procedure and follow-up visits. For AS, our protocol involves digital rectal examination (DRE) and PSA testing every 3 months for first 2 years and every 6 months thereafter. Transrectal ultrasound (TRUS)-guided biopsies are performed yearly. Some urologists recommend spacing the biopsies by 1-3 years. Medicare reimbursement values were used. The urologist reimbursements for a follow-up visit, prostate biopsy, open TP and robotic TP are $72,$595, $1905 and$2939, respectively. We also corrected for a 15% chance of having TP after being on AS. The cumulative reimbursements from open TP and following the patient up to 10 years are approximately $2121 (1 year),$2265 (2 years), $2697 (5 years) and$3057 (10 years). For robotic TP, the urologist reimbursements are $3155 (1 year),$3259 (2 years), $3731 (5 years) and$4091 (10 years). For AS, the urologist reimbursements are $883 (1 year),$1766 (2 years), $4269 (5 years) and$7964 (10 years). The urologist reimbursement from AS and TP become nearly equal between 3 and 4 years follow-up, subsequently AS attains higher reimbursement