Female Gender Is an Age-dependent Negative Prognostic Factor for Patients with Upper Tract Urothelial Carcinoma.

AIM: To analyze female gender as a possible age-dependent prognostic factor for overall (OS) and cancer-specific survival (CSS) in patients with upper urinary tract urothelial carcinoma (UUTUC) after radical nephroureterectomy (RNU). PATIENTS AND METHODS: A total of 167 men and 101 women with UUTUC treated with RNU with bladder cuff resection at our clinic were retrospectively analyzed. Female patients were divided into pre- and post-menopausal groups and compared against male patients of the same age. We used a cut-off age of 59 years or more as a surrogate for the post-menopausal hormonal status of women. Kaplan-Meier analyses and multivariate Cox proportional hazards regression analyses were performed to analyze gender as a possible prognostic factor of OS and CSS. RESULTS: Women aged 59 years or more had a significantly worse CSS with an average of 231 months after RNU compared to 303 months for their male counterparts (p=0.011). Univariate Cox regression analysis showed a 2.44-fold higher risk of death (p=0.013), while multivariate analyses, adjusted for tumor stage and tumor grade, showed a 2.92-fold higher risk (p=0.011) of cancer-specific death for women aged 59 years or more. CONCLUSION: Female gender is an age-dependent prognostic factor for CSS for patients with UUTUC treated with RNU.

Piwi-like 1 and 4 gene transcript levels are associated with clinicopathological parameters in renal cell carcinomas.

Piwi-like gene family members (Piwil 1-4) are considered stem cell-associated genes/proteins. These are expressed predominantly in germline cells, but are re-expressed in different tumors. Piwil 1-4 gene expression has not previously been studied and correlated with clinicopathological parameters in renal cell carcinomas (RCC). The Piwil 1-4 transcript levels were analyzed by quantitative real-time PCR in 73 clear cell RCC (ccRCC) tissues and corresponding normal tissues. The transcript levels of Piwil 1, 2 and 4 were strongly and significantly correlated with each other, in both the tumor tissues and the normal tissues (P<0.001; Spearman's rank test). Piwil 4 gene expression was significantly higher in the ccRCC tissues than that in the corresponding normal renal tissues (P<0.001; Wilcoxon signed-rank test). When the ccRCC patient cohort was divided according to the median Piwil 1-4 expression into low- and high-expression groups and according to age into younger (≤64years) and older patient groups (>64years), the younger patients displayed significantly higher levels of Piwil 1 mRNA in comparison to the older patients (P=0.010; Fisher's exact test). Interestingly, Piwil 1 expression was left-right polarized in the normal tissues but not in the tumor tissues (P=0.004; Fisher's exact test). Altogether, associations were determined between the Piwi-like family member expression levels and clinicopathological parameters of ccRCC, suggesting a potential role for these genes/proteins in ccRCC diagnostics and tumorigenesis as well as in renal tissue embryology.

Quality assured health care in certified breast centers and improvement of the prognosis of breast cancer patients.

BACKGROUND: Increasing effort has been put in the implementation and certification of breast centers in order to establish standardized, quality assured health care for breast cancer patients. The aim of this analysis was to investigate whether patients treated in certified breast centers (CBC) have a favorable prognosis as compared to patients treated outside of certified breast treatment units. PATIENTS AND METHODS: The data of 3,940 patients with invasive nonmetastatic breast cancer were analyzed with regard to differences in patient and tumor characteristics and crude overall survival according to diagnosis in or outside CBC in Middle Franconia, Germany. Patient, tumor, and follow-up data were obtained from the clinical cancer registry. RESULTS: Patients in CBC were younger, and had lower disease stages and lower grading. Independent of the effects of these variables on overall survival, being treated at a CBC added to the prediction of overall survival. Patients treated at a CBC had a hazard ratio of 0.70 (95% confidence interval 0.52-0.93) in the adjusted Cox model. CONCLUSIONS: Independent from common prognostic factors, diagnosis and treatment of breast cancer at a CBC improves the prognosis of patients. It can be hypothesized that this effect is mediated through quality assured health care provided by the certification process.

Histopathologic features and microsatellite instability of cancers of the papilla of vater and their precursor lesions.

The prevalence and development of microsatellite instability (MSI) and underlying mismatch repair (MMR) deficiency in the carcinogenesis of adenocarcinomas of the papilla of Vater and their precursor lesions are not well established. We analyzed 120 ampullary adenomas (31 pure adenomas and 89 carcinoma-associated adenomas) and 170 pure adenocarcinomas for MSI, immunohistochemical expression of MMR proteins and specific histopathologic features. The most common histologic subtype was intestinal (46.5%), followed by pancreatobiliary (23.5%), poorly differentiated adenocarcinomas (12.9%), intestinal-mucinous (8.2%), and invasive papillary carcinomas (5.3%). Eight of 89 adenomas (9%) and 15/144 carcinomas (10%) showed high microsatellite instability (MSI-H), 10/89 adenomas (11%) and 5/144 carcinomas (4%) showed low microsatellite instability (MSI-L), and 71/89 adenomas (80%) and 124/144 carcinomas (86%) were microsatellite stable (MSS). MSI analysis from carcinomas contiguous with an adenomatous component (n=54) exhibited concordant results in 6/8 (75%) MSI-H and 42/46 (91.3%) MSS tumors. Of 14 carcinomas with MSI-H, 7 showed loss of MLH1 and 5/6 (83%) MLH1 promoter methylation, and 2 carcinomas showed simultaneous loss of MSH2 and MSH6. Two carcinomas and 3 adenomas with MSI-H revealed exclusive loss of MSH6. MSI-H cancers were significantly associated with intestinal mucinous subtype (P<0.001), high tumor grade (P=0.003), expansive growth pattern (P=0.044), and marked lymphoid host response (P=0.004). Patients with MSI-H carcinoma had a significantly longer overall survival (P=0.0082) than those with MSI-L or MSS tumors. Our findings indicate that the MSI-phenotype is an early event, which develops at the stage of adenoma and is reliably detectable in the precursor lesion. The MMR deficient molecular pathway of carcinogenesis is associated with a histopathologic phenotype in ampullary cancer, similar to the one that has been well described in colon cancer.