Predictor Of Disease-free Interval Research Articles

Abstract 4187: Phospho-Akt status as a predictor of disease free interval in patients with muscle invasive transitional cell carcinoma of the bladder

Abstract Background: Akt is an ubiquitous signaling molecule that is associated with a wide array of biological effects including cell growth and proliferation. The dysregulation of Akt has been associated with cancer cell transformation, invasion and metastasis. While the roles of mutations in FGFR3, p53 and Ras have been the focus of the majority of studies of Transitional cell carcinoma (TCC) of the bladder, recent evidence suggests a link between the Akt pathway and the progression of TCC. Mutations in Akt pathway members have been identified in subsets of bladder TCCs, and Akt activation in TCC cell lines confers resistance to chemotherapeutics and promotes invasion in vitro. This led us to hypothesize that activated Akt may be an important biomarker in the progression of muscle invasive TCC. Methods: Tissue was obtained from 67 patients who had undergone radical cystectomy procedures for treatment of muscle invasive TCC. Tissue sections were taken from paraffin embedded samples and subjected to immunohistochemical analysis with anti Akt antibody to detect the activated form of Akt. A database of patient demographics, disease, treatment and survival parameters was generated and used to correlate 4, 12, 24 and 36 month disease-free intervals (DFI). Results: 53 of the 67 patients had sufficient follow-up to allow for DFI analysis. Of these 53 patients, 48 stained positively for pAkt, while 5 stained negatively. None of the pAkt negative patients had recurrent disease, while the pAkt negative patients suffered cumulative recurrence in 10, 19, 24, and 25 of the 48 patients at 4, 12, 24 and 36 months respectively. Chi square analysis reveals statistically significant differences in recurrence rates between pAkt negative and negative patients at 24 (p=0.0235) and 36 months (p=0.016). Tumor stage and nodal status were also strong predictors of recurrence. Conclusions: pAkt negative patients were found to have a significantly better prognosis for TCC recurrence, which indicates that pAkt status could be useful in helping to determine the prognosis for patients with muscle invasive TCC. These results lead us to speculate that the use of a serine threonine kinase inhibitor may prove to be therapeutically beneficial for TCC patients undergoing concurrent chemotherapy for their disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4187. doi:10.1158/1538-7445.AM2011-4187

Expression of Bcl-2 family proteins and associated clinicopathologic factors predict survival outcome in patients with oral squamous cell carcinoma

The aims of this study were to assess the expression levels of three proteins involved in apoptosis--Bcl-2, Bcl-X, and Bax--and evaluate their relationship with clinicopathologic features and survival in oral squamous cell carcinoma (OSCC). Immunohistochemistry was used to evaluate protein expression in 53 primary OSCCs treated by radical surgery with free margins at a single institution in 1999. Histologic specimens were graded and analyzed for perineural invasion, lymphocytic infiltrate, and pattern of invasion. Digital image analysis was performed to quantify immunostaining. Survival was analyzed using the Kaplan-Meier method and Cox's proportional hazard model. Cancer-specific 5-year survival (CSS) was 61% (56% overall survival (OS), and 51% disease-free interval (DFI)). Kaplan-Meier analysis identified pathologic stage (p=0.0007, log-rank test, OS), negative nodes status (pN) (p<0.0001, log-rank test, OS), presence of lymphocytic infiltrate (p=0.0084, log-rank test, OS), and high Bax expression (p=0.025, log-rank test, OS) to each be associated with both better OS and CSS. Tongue tumors (p=0.0179, log-rank test), worst pattern of invasion (p=0.0293, log-rank test), lack of lymphocytic infiltrate (p=0.0328, log-rank test), perineural invasion (p=0.0448, log-rank test), poorly differentiated tumors (p=0.0318, log-rank test), and low Bcl-X expression (p=0.044, log-rank test) were all associated with a low DFI. Cox regression found pN, lymphocytic infiltrate, and Bax expression to be independent prognostic factors for OS and CSS, whereas lymphocytic response and tongue tumors were predictors of DFI. Bcl-2 expression emerged as an independent marker of favorable CSS. Lymphocytic infiltrate was the most meaningful histopathologic parameter in survival analysis, whereas expression of Bcl-2 family members seems to be an important marker of a favorable prognosis in OSCC.

A comparison between histological grade and nuclear morphometry for predicting the clinical outcome of localized renal cell carcinoma.

To determine the interrelationship of histological grade and nuclear morphometry and to compare their prognostic significance in patients with localized renal cell carcinoma (RCC). A retrospective prognostic study of 39 patients with localized (pT1, pT2) RCC was performed. Conventional histological grade and nuclear morphometry were assessed independently and the correlation between these grading systems and their impact on the patients' outcome were evaluated. Histological grade and the nuclear morphometric variables were significantly correlated: the strongest association was that between grade and the nuclear regularity factor. The best predictor of disease-free interval and survival (by univariate analysis) was the combination of nuclear area and nuclear elongation factor, followed by conventional tumour grade, nuclear elongation factor, nuclear regularity factor and nuclear area. However, a multivariate analysis showed that the only independent prognosticator for survival was the combination of nuclear area and nuclear elongation factor. This study indicates that nuclear morphometry is prognostically superior to histological grade in patients with localized RCC.

The role of nuclear morphometry for predicting disease outcome in patients with localized renal cell carcinoma.

More than one-third of patients with localized renal cell carcinoma (RCC) will have disease progression after nephrectomy. Present histopathologic variables cannot accurately predict the outcome of individual patients. Nuclear morphometry was performed by an image analyzer on histologic sections from 39 specimens of pathologic T1 and T2 classification RCC. All patients underwent radical nephrectomy and were followed for a mean of 7.6 years. A univariate analysis and then a multivariate stepwise regression method were used to correlate results with patients' outcome. The best predictors of disease free interval were mean nuclear elongation factor (MNEF) (P = 0.023), mean nuclear regularity factor (MNRF) (P = 0.034), and mean nuclear area (MNA) (N = 0.038). Univariate analysis identified a significant correlation between patient survival and MNEF (P = 0.009), MNRF (P = 0.020) and MNA (P = 0.023). Combination of MNEF and MNA was even more strongly associated with survival (P = 0.0013). Multivariate analysis revealed that MNA (P = 0.044) and MNEF (P = 0.045) correlated independently with survival. These results suggest that nuclear morphometry provides objective independent prognostic information for patients with localized RCC.