PATIENTS AND METHODS: A systematic search was conducted according to the PRISMA guidelines for studies reporting on outcomes after TMT and RC. A total of 57 studies including 30,293 patients were included. The 10-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates for TMT and RC were assessed.
RESULTS: The mean 10-year OS was 30.9% for TMT and 35.1% for RC (P = 0.32). The mean 10-year DSS was 50.9% for TMT and 57.8% for RC (P = 0.26). NAC was administered before therapy to 453 (13.3%) of 3,402 patients treated with TMT and 812 (3.0%) of 27,867 patients treated with RC (P<0.001). Complete response (CR) was achieved in 1,545 (75.3%) of 2,051 evaluable patients treated with TMT. A 5-year OS, DSS, and RFS after CR were 66.9%, 78.3%, and 52.5%, respectively. Downstaging after transurethral bladder tumor resection or NAC to stage ≤pT1 at RC was reported in 2,416 (29.1%) of 8,311 patients. NAC significantly increased the rate of pT0 from 20.2% to 34.3% (P = 0.007) in cT2 and from 3.8% to 23.9% (P<0.001) in cT3-4. A 5-year OS, DSS, and RFS in downstaged patients (≤pT1) at RC were 75.7%, 88.3%, and 75.8%, respectively.
CONCLUSION: In this analysis, the survival outcomes of patients after TMT and RC for MIBC were comparable. Patients who experienced downstaging after NAC and RC exhibited improved survival compared to patients treated with RC only. Best survival outcomes after TMT are associated with CR to this approach.
METHODS: A total of 234 invasive cervical carcinomas (152 squamous cell carcinomas, 61 adenocarcinomas and 21 adenosquamous carcinomas) and 16 cervical intraepithelial neoplasia (CIN) I, six CIN II and 25 CIN III were immunohistochemically studied for p53.
RESULTS: p53 was detected more frequently in CIN and invasive carcinoma (100% of CIN I, 74.2% CIN II + III and 70.1% invasive carcinoma) compared with benign cervices (P< 0.001); however, only three squamous cell carcinomas, 11 adenocarcinomas and two adenosquamous carcinomas exhibited p53 expression in >75% of tumour nuclei. Six of the 11 adenocarcinomas and both adenosquamous carcinomas were poorly differentiated compared with one of the three squamous carcinomas. p53 immunoreactive cells were randomly distributed in invasive carcinoma, confined to the lower third of the epithelium in CIN I, reached the middle third in 20% of CIN II and upper third in 16.6% of CIN III.
CONCLUSIONS: Assuming that p53 immunoreactivity indicates gene mutation when the majority (> 75%) of neoplastic cells express p53, p53 mutations would seem uncommon in cervical carcinogenesis. Nonetheless, glandular malignancies, in particular poorly differentiated variants, may show a higher frequency of mutation. p53 was detected more frequently in CIN I compared with CIN II/III and invasive carcinoma which may be due to p53 protein degradation following interaction with high risk human papillomavirus E6 protein in CIN II/III and invasive carcinoma.
OBJECTIVES: To identify the epidemiological profile and prognostic factors of survival.
MATERIALS AND METHODS: A list of endometrial cancer patients in 2000-2011 was obtained from the hospital Record Department. Only cases confirmed by histopathology examination were included. We excluded those with incomplete medical records or referral cases. Simple and multiple Cox regression approaches were used for data analysis.
RESULTS: Only 108 cases were included with a mean (SD) age of 62.7 (12.3) years, with 87.0% Malay ethnicity. Grade of cancer was: 29.1% grade 1, 43.7% grade 2 and 27.2% grade 3. The majority of patients had non-endometrioid type (60.2%), with myometrial invasion (82.2%) and lymphovascular invasion (57.3%). The significant prognostic factors were age (HR 1.05; 95% CI: 1.02, 1.08, p=0.002) and having lymphovascular invasion (HR 2.15; 95% CI: 1.08, 4.29; p=0.030).
CONCLUSIONS: Endometrial cancer patients should be diagnosed earlier to reduce the risk of mortality. The public should be given education on the signs and symptoms of the disease.
METHODOLOGY: Using a cross-sectional design, invasive breast carcinoma of no special type (NST) and HER2 IHC scores of 2+ and 3+ cases were selected over a 50-month period in Hospital Sultanah Bahiyah (HSB), Alor Setar. IHC staining for HMGCR was performed on paraffin-embedded tissues at the Pathology Laboratory, Hospital Universiti Sains Malaysia (HUSM), Kubang Kerian using the standard staining procedure. The results were correlated with the patient's demographic and clinicopathological data.
RESULTS: A total of 59 cases of HER2 IHC 2+ and 3+ invasive breast carcinoma were identified. The cases were predominant in young Malay women with tumours smaller than 50mm, higher grade and positive for lymphovascular invasion, axillary lymph nodes involvement and ER/PR expressions. HMGCR was positively expressed in HER2 IHC 2+ and 3+ breast cancer cases, which the staining intensities varied from weak, moderate to strong. Majority of the cases were scored 1+ for HMGCR expression. A low-positive HMGCR was more likely to be associated with less favourable outcomes of patients with HER2 IHC 2+ and 3+. However, the associations were statistically not significant.
CONCLUSION: A study in a larger cohort of tumour samples is needed to further validate HMGCR expression as a potential prognostic biomarker for HER2 positive breast cancer. It is also suggested that all the HER2 IHC 2+ and 3+ cases need to be gene amplified using FISH analysis.
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METHODS: In total, 80 samples of tumor and matched adjacent normal tissues were collected from breast cancer patients at Seberang Jaya Hospital (SJH) and Kepala Batas Hospital (KBH), both in Penang, Malaysia. The protein expression profiles of breast cancer and normal tissues were mapped by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The Gel-Eluted Liquid Fractionation Entrapment Electrophoresis (GELFREE) Technology System was used for the separation and fractionation of extracted proteins, which also were analyzed to maximize protein detection. The protein fractions were then analyzed by tandem mass spectrometry (LC-MS/MS) analysis using LC/MS LTQ-Orbitrap Fusion and Elite. This study identified the proteins contained within the tissue samples using de novo sequencing and database matching via PEAKS software. We performed two different pathway analyses, DAVID and STRING, in the sets of proteins from stage 2 and stage 3 breast cancer samples. The lists of molecules were generated by the REACTOME-FI plugin, part of the CYTOSCAPE tool, and linker nodes were added in order to generate a connected network. Then, pathway enrichment was obtained, and a graphical model was created to depict the participation of the input proteins as well as the linker nodes.
RESULTS: This study identified 12 proteins that were detected in stage 2 tumor tissues, and 17 proteins that were detected in stage 3 tumor tissues, related to their normal counterparts. It also identified some proteins that were present in stage 2 but not stage 3 and vice versa. Based on these results, this study clarified unique proteins pathways involved in carcinogenesis within stage 2 and stage 3 breast cancers.
CONCLUSIONS: This study provided some useful insights about the proteins associated with breast cancer carcinogenesis and could establish an important foundation for future cancer-related discoveries using differential proteomics profiling. Beyond protein identification, this study considered the interaction, function, network, signaling pathway, and protein pathway involved in each profile. These results suggest that knowledge of protein expression, especially in stage 2 and stage 3 breast cancer, can provide important clues that may enable the discovery of novel biomarkers in carcinogenesis.
MATERIALS AND METHODS: We identified women diagnosed with ILC or IDLC. We selected the patients who had preoperative breast MRI. For each patient we identified the areas of multifocal, multicentric, or contralateral disease not visible to standard exams and detected by preoperative MRI. We analyzed the potential correlation between additional cancer areas and histological cancer markers.
RESULTS: Of the 155 women who met our inclusion criteria, 93 (60%) had additional cancer areas detected by MRI. In 61 women, 39,4% of the overall population, the additional cancer areas were confirmed by US/tomosynthesis second look and biopsy. Presurgical MRI staging changed surgical management in the 37,4% of the patients. Only six patients of the overall population needed a reoperation after the initial surgery. No statistically significant correlation was found between MRI overestimation and the presence of histological peritumoral vascular/linfatic invasion. No statistically significant correlation was found between additional cancer areas and histological cancer markers.
CONCLUSIONS: Our study suggests that MRI is an important tool in the preoperative management and staging of patients affected by lobular or ductolobular invasive carcinoma.
MATERIALS AND METHODS: ER+ MCF7 and ER- MDA-MB-231 cell lines were subjected to two-dimensional electrophoresis (2-DE) and spots of interest were identified by matrix-assisted laser desorption/ionization time of- flight/time- of-flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis after downregulation of RhoGDIα using short interfering RNA (siRNA) and upregulated using GFP-tagged ORF clone of RhoGDIα.
RESULTS: The results showed a total of 35 proteins that were either up- or down-regulated in these cells. Here we identifed 9 and 15 proteins differentially expressed with silencing of RhoGDIα in MCF-7 and the MDA-MB-231 cells, respectively. In addition, 10 proteins were differentially expressed in the upregulation of RhoGDIα in MCF7, while only one protein was identified in the upregulation of RhoGDIα in MDA-MB-231. Based on the biological functions of these proteins, the results revealed that proteins involved in cell migration are more strongly altered with RhoGDI-α activity. Although several of these proteins have been previously indicated in tumorigenesis and invasiveness of breast cancer cells, some ohave not been previously reported to be involved in breast cancer migration. Hence, these proteins may serve as useful candidate biomarkers for tumorigenesis and invasiveness of breast cancer cells.
CONCLUSIONS: Future studies are needed to determine the mechanisms by which these proteins regulate cell migration. The combination of RhoGDIα with other potential biomarkers may be a more promising approach in the inhibition of breast cancer cell migration.
METHODS: We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort.
FINDINGS: We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group.
INTERPRETATION: PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy.
FUNDING: Samsung Biomedical Research Institute.
METHODS: Gene expression of IL-6 and IL-6Rα in PSC and PDAC cells was measured with qRT-PCR. The role of PSC-secreted IL-6, JAK/Stat3 signaling, and Nrf2 mediation on EMT-related genes expression was also examined with qRT-PCR. EMT phenotypes were assessed with morphological change, wound healing, migration, and invasion.
RESULTS: PSC expressed higher mRNA levels of IL-6 but lower IL-6Rα compared to PDAC cells. Neutralizing IL-6 in PSC secretion reduced mesenchymal-like morphology, migration and invasion capacity, and mesenchymal-like gene expression of N-cadherin, vimentin, fibronectin, collagen I, Sip1, Snail, Slug, and Twist2. Inhibition of JAK/Stat3 signaling induced by IL-6 repressed EMT and Nrf2 gene expression. Induction of Nrf2 activity by tert-butylhydroquinone (tBHQ) increased both EMT phenotypes and gene expression (N-cadherin, fibronectin, Twist2, Snail, and Slug) repressed by IL-6 neutralizing antibody. Simultaneous inhibition of Nrf2 expression with siRNA and Stat3 signaling further repressed EMT gene expression, indicating that Stat3/Nrf2 pathway mediates EMT induced by IL-6.
CONCLUSIONS: IL-6 from PSC promotes EMT in PDAC cells via Stat3/Nrf2 pathway.
GENERAL SIGNIFICANCE: Targeting Stat3/Nrf2 pathway activated by PSC-secreted IL-6 may provide a novel therapeutic option to improve the prognosis of PDAC.
MATERIALS AND METHODS: Formalin-fixed paraffin- embedded tumour tissue of 144 no special type (NST) invasive breast carcinomas histologically diagnosed between January 2009 and December 2012 in Hospital Sultanah Bahiyah, Alor Setar, Kedah were immunostained with COX-2 antibody. COX-2 overexpression was analysed against demographic data, hormone receptor status, HER2- neu overexpression, histological grade, tumour size and lymph node status.
RESULTS: COX-2 was overexpressed in 108/144 (75%) tumours and was significantly more prevalent (87%) in hormone receptor-positive tumours. There was no correlation between COX-2 overexpression and HER2/neu status. Triple negative cancers had the lowest prevalence (46%) (p<0.05). A rising trend of COX-2 overexpression with increasing age was observed. There was a significant inverse relationship with tumour grade (p<0.05), prevalences being 94%, 83% and 66% in grades 1, 2 and 3 tumours, respectively. A higher prevalence of COX-2 overexpression in smaller size tumours was observed but this did not reach statistical significance. There was no relationship between COX-2 expression and lymph node status.
CONCLUSIONS: This study did not support the generally held notion that COX-2 overexpression is linked to poor prognosis, rather supporting a role in tumorigenesis. Larger scale studies with outcome data and basic studies on cancer pathogenetic pathways will be required to cast further light on whether COX-2 inhibitors would have clinical utility in cancer prevention or blockage of cancer progression. In either setting, the pathological assessment for COX-2 overexpression in breast cancers would have an important role in the selection of cancer patients for personalized therapy with COX-2 inhibitors.