Risk Factor Analysis for Developing Major Complications Following Esophageal Surgery-A Two-Center Study.

BACKGROUND: Esophagectomy carries a high risk of morbidity and mortality compared to other major surgeries. With the aim of creating an easy-to-use clinical preoperative risk assessment tool and to validate previously described risk factors for major complications following surgery, esophagectomies at two tertiary medical centers were analyzed. METHODS: A total of 450 patients who underwent esophagectomy for esophageal carcinoma at the University Medical Centre, Hamburg, or at the Medical Center University Duisburg-Essen, Germany (January 2008 to January 2020) were retrospectively analyzed. Epidemiological and perioperative data were analyzed to identify the risk factors that impact major complication rates. The primary endpoint of this study was to determine the incidence of major complications. RESULTS: The mean age of the patients was 63 years with a bimodal distribution. There was a male predominance across the cohort (81% vs. 19%, respectively). Alcohol abuse (p = 0.0341), chronic obstructive pulmonary disease (p = 0.0264), and cardiac comorbidity (p = 0.0367) were associated with a significantly higher risk of major complications in the multivariate analysis. Neoadjuvant chemotherapy significantly reduced the risk of major postoperative complications (p < 0.0001). CONCLUSIONS: Various patient-related risk factors increased the rate of major complications following esophagectomy. Patient-tailored prehabilitation programs before esophagectomy that focus on minimizing these risk factors may lead to better surgical outcomes and should be analyzed in further studies.

Failure of a Multi-Centric Clinical Trial Investigating Neoadjuvant Radio-Chemotherapy in Resectable Pancreatic Carcinoma (NEOPA-NCT01900327)-Which Lessons Are Learnt?

BACKGROUND: A significant number of clinical trials must be prematurely discontinued due to recruitment failure, and only a small fraction publish results and a failure analysis. Based on our experience on conducting the NEOPA trial on neoadjuvant radiochemotherapy for resectable and borderline resectable pancreatic carcinoma (NCT01900327-funded by the German Federal Ministry of Education and Research-BMBF), we performed an analysis of potential reasons for recruitment failure and general problems in conducting clinical trials in Germany. METHODS: Systematic analysis of environmental factors, trial history, conducting and funding in the background of the published literature. RESULTS: The recruitment failure was based on various study-specific conceptional and local environmental aspects and in peculiarities of the German surgical study culture. General reservations against a neo-adjuvant study concept combined with game changing scientific progresses during the long-lasting planning and funding phase have led to a reduced interest in the trial design and recruitment. CONCLUSIONS: Trial planning and conducting should be focused, professionalized and financed on a national basis. Individual interests must be subordinated to reach the goal to perform more relevant and successful clinical trials in Germany. Bureaucratic processes must be further fastened between a trial idea and the start of a study.

RAI3 expression is not associated with clinical outcomes of patients with non-small cell lung cancer.

PURPOSE: Retinoic acid inducible protein 3 (RAI3) has been suggested as prognostic biomarker in several cancer types. The present study aimed to examine the role of RAI3 expression in non-small cell lung cancers (NSCLCs). METHODS: RAI3 protein expression was evaluated by immunohistochemistry in tissue microarray (TMA) sections from a retrospective cohort of more than 600 surgically resected NSCLCs and results were compared with clinicopathological features and follow-up data. RESULTS: While membranous RAI3 immunostaining was always strong in benign lung, strong RAI3 staining was only detectable in 14.7% of 530 interpretable NSCLCs. Within NSCLC subtypes, immunostaining intensity for RAI3 was significantly decreased in large cell lung cancers (LCLCs) and squamous cell carcinomas (SQCCs) relative to lung adenocarcinomas (LUACs) (P < 0.0001 each). However, RAI3 staining was neither associated with pathological features of NSCLCs nor with survival of patients (P = 0.6915). CONCLUSION: Our study shows that RAI3 expression was not associated with clinical outcomes of NSCLC patients and cannot be considered as prognostic marker in lung cancer patients.

Potential role of the bitter taste receptor T2R14 in the prolonged survival and enhanced chemoresponsiveness induced by apigenin.

Bitter taste receptors (T2Rs) are G protein­coupled receptors originally detected in the gustatory system. More recently, T2Rs have been shown to be expressed in extra­oral cells eliciting non­gustatory functions. Emerging evidence has suggested a potential role for T2R signaling in diverse pathophysiological conditions, including cancer. -The aim of the present study was to evaluate the expression of T2R14 in pancreatic ductal adenocarcinoma (PDAC) and to assess its involvement in the anticancer effects induced by apigenin, a natural ligand of T2R14. For this purpose, T2R14 expression was explored in PDAC tumor tissue and tumor­derived cell lines. Using the cell lines expressing the highest levels of T2R14, its effects on chemoresponsiveness and migration upon activation with apigenin were investigated in vitro. To the best of our knowledge, the present study was the first to confirm the expression of the T2R family member T2R14 in PDAC. Patients with relatively high levels of T2R14 expression exhibited significantly prolonged overall survival compared with that of patients with low T2R14 expression. Furthermore, novel functions for apigenin were revealed; notably, apigenin was shown to elicit cytotoxic, anti­migratory and chemosensitizing effects to 5­fluoruracil (5­FU) and to 5­FU, leucovorin, irinotecan and oxaliplatin in pancreatic cancer cells. In conclusion, the present study extended the evidence for the anticancer effects of apigenin and strongly indicated the functional relevance of T2R14 in PDAC, even though their respective underlying pathways appear to be independent of each other.

Importance of computed tomography muscle quality and continuous versus cut-off-based sarcopenia detection in major hepatic surgery.

Background: The role of the computed tomography (CT)-derived skeletal muscle index (SMI) as a parameter of muscle quantity on the outcome after major liver resection remains contradictory and that of the muscle radiodensity attenuation (MRA) as a parameter of muscle quality has not been sufficiently evaluated. This observational study aimed to investigate the influence of metric SMI and MRA values and cut-off-based CT sarcopenia detection on liver-surgery specific complications measured by the new FABIB (liver failure, ascites, biliary leakage, infection, bleeding) score and survival after hemihepatectomy. Methods: A total of 183 patients with major hepatectomy were retrospectively included. The SMI and MRA were determined from the abdominal muscle area of preoperative CT scans. Patients were classified as sarcopenic by the SMI and MRA cut-off values of Prado et al., Martin et al., and van der Werf et al. Postoperative complications were documented according to the Clavien-Dindo classification and FABIB score. The relation of the continuous, non-categoric SMI and MRA values and of the cut-off-based sarcopenia detection to the postoperative complications and survival was analyzed by multivariable linear, logistic, and Cox proportional hazards regression. Results: A higher MRA was associated with less severe postoperative complications in the Clavien-Dindo [-0.59 (95% CI: -0.95 to -0.23), P=0.002] and the FABIB score [-0.65 (95% CI: -1.19 to -0.12), P=0.017]. An increase of the SMI did not result in less severe complications in the Clavien-Dindo [0.14 (95% CI: -0.27 to 0.55), P=0.503] or FABIB score [0.17 (95% CI: -0.42 to 0.76), P=0.572]. For patients classified as sarcopenic by the cut-off-based systems no relevant relation to postoperative complications was found. Overall survival was better for a higher MRA [hazard ratio (HR): 0.75 (95% CI: 0.58-0.97), P=0.029], as long-term survival was for a higher SMI [HR: 0.68 (95% CI: 0.47-0.96), P=0.031]. Only below van der Werf's MRA cut-off the probability of overall and long-term survival was reduced [HR: 2.32 (95% CI: 1.18-4.54), P=0.015; 2.68 (95% CI: 1.25-5.74), P=0.011]. Conclusions: The MRA has a stronger influence on complications in the Clavien-Dindo classification and the liver-surgery specific FABIB score than the SMI. Continuous, non-categoric MRA and SMI values are superior to cut-off-based systems in predicting the outcome after major hepatic surgery.

Completion of FLOT Therapy, Regardless of Tumor Regression, Significantly Improves Overall Survival in Patients with Esophageal Adenocarcinoma.

Esophageal cancer is the eighth most common cancer worldwide, with poor prognosis and high mortality. The combination of surgery and systemic therapy provide the best chances for long-term survival. The purpose of this study was to analyze the impact of the FLOT protocol on the overall survival of patients following surgery for esophageal adenocarcinoma, with a focus on the patients who did not benefit in terms of pathological remission from the neoadjuvant therapy. A retrospective analysis of all the patients who underwent esophagectomies from 2012 to 2017 for locally advanced adenocarcinomas of the esophagus at a tertiary medical center was performed. The results show that the completion of systemic therapy, regardless of the tumor regression grading, had a significant positive impact on the overall survival. The patients with complete regression and complete systemic therapy showed the best outcomes. Anastomotic insufficiency did not negatively impact the long-term survival, while complications of the systemic therapy led to significantly reduced overall survival. We conclude that adjuvant systemic therapy should, when possible, always be completed, regardless of the tumor regression, following an esophagectomy.

[Solid pseudopapillary neoplasms of the pancreas : Diagnostics, surgical treatment and postoperative outcome]. / Solid-pseudopapilläre Neoplasien des Pankreas : Diagnostik, chirurgische Therapie und postoperatives Outcome.

BACKGROUND: Malignant solid pseudopapillary neoplasms (SPN) are rare tumor entities of the pancreas. The prognosis for SPN is generally excellent, although some tumors have malignant potential and tend to metastasize or relapse. OBJECTIVE: The aim was to investigate whether there are histopathological or surgical risk factors that enable the biological potential of SPN to be estimated. PATIENTS AND METHODS: Data from patients with SPN treated in two large German pancreas centers from 2009 to 2018 were evaluated with respect to the occurrence of SPN, surgical management, histopathological tumor characteristics and the postoperative outcome. RESULTS: A total of 22 patients with SPN (17 women, 5 men) were operated on. The median age of the patients was 37 years (range 19-69 years). At the time of surgery 20 patients showed tumor growth limited to the pancreas. A female patient with recurrence of an externally resected SPN had lymph node involvement. Another female patient had a hepatic metastatic recurrence (Union Internationale contre Cancer (UICC) stage IV) of an externally resected SPN. Although all patients survived recurrence-free during the follow-up, this patient developed liver metastases again. The survival rate up to the end of the follow-up (median 43 months; range 1-132 months) of this study was 100%. CONCLUSION: There is a lack of knowledge of the possible parameters that can be used to predict the biological behavior of SPN. Apart from an increased likelihood of recurrence after resection of an SPN recurrence, no clear risk factors could be identified in the examined patient collective that could indicate an increased malignant potential and a possibly poorer outcome. Only a radical surgical resection with lymphadenectomy enables a reliable assessment of the tumor stage and the removal of possibly affected lymph nodes, which could be the cause of a recurrence if left intact.

Increased lysophosphatidylcholine acyltransferase 1 expression is unrelated to prognosis of esophageal cancer patients.

INTRODUCTION: Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has repeatedly been suggested to be associated with tumorigenesis. To evaluate the role of LPCAT1 in esophageal cancer, LPCAT1 immunostaining was analyzed on a tissue microarray containing samples from esophageal cancer patients. RESULTS: In benign esophageal tissue, LPCAT1 staining was detectable in low intensities. LPCAT1 staining was increased in malignant as compared to benign esophageal tissue and was found in high intensity in 26.4% of 288 interpretable esophageal adenocarcinomas (EACs) and in 23.2% of 211 squamous cell carcinomas (ESCCs). Increased LPCAT1 staining was linked to undifferentiated tumor grading in both subtypes of EACs and ESCCs (p = 0.0273 and p = 0.0085). CONCLUSION: However, LPCAT1 was not associated with prognosis of EAC and ESCC patients (p = 0.6838 and p = 0.4695) and thus cannot be considered a prognostic biomarker in esophageal cancers.

First in Literature Intraneuronal Sacral Nerve Stimulation for Fecal Incontinence After Robotic-Assisted En-Bloc Sacrectomy with Transection of Nerve Roots.

BACKGROUND: En-bloc sacrectomy is the treatment of choice for patients affected by sacral chordoma. It is a radical surgical procedure, which has to face the problem of handling fragile anatomic structures, such as the internal iliac vessels and the sacral nerve roots, with the risk of causing bowel, bladder, and sexual dysfunction. The combined anterior-posterior approach allows for a safer dissection of the tumor from the mesorectal fascia than the mere posterior approach, especially for tumors extending proximally to S3. Robotic surgery can improve the safety of the procedure. Sacral nerve stimulation is an accepted therapeutic option for fecal incontinence and may be used to treat postoperative incontinence. CASE PRESENTATION: We report on a patient affected by sacral chordoma with en-bloc sacrectomy preceded by a robotic-assisted dissection of the mesorectal fascia and on managing the postoperative fecal incontinence by implanting a sacral nerve stimulator on the first postoperative day. To our knowledge this is the first such procedure in the literature. CONCLUSIONS: From our experience, a robotic anterior approach increases safety for the organs in the pelvis when performing a sacrectomy. Moreover, a sacral nerve stimulator should be considered to manage neurologic complications following transection of nerve roots after sacrectomy.

C-Reactive Protein in the Prediction of Localization of Gastrointestinal Perforation.

AIM: Information regarding the localization of the anatomic site of gastrointestinal (GI) tract perforation is essential for the following surgical procedure. The purpose of this study was to evaluate the significance of C-reactive protein (CRP) and other circulating markers for the prediction of the localization of intra-abdominal hollow organ perforation. METHODS: Measurements of serum markers were analyzed in 423 patients with GI tract perforations, who were divided according to the intraoperative diagnosis into colorectal and upper GI tract perforation groups. RESULTS: Levels of CRP were higher in patients with colorectal perforations than in upper GI tract perforations (p < 0.001). Moreover, high levels of CRP were associated with increased mortality of patients with hollow organ perforations (p = 0.009), which was largely driven by the subset of patients with perforations of the upper GI tract (p = 0.001). CONCLUSION: Increased CRP levels predict worse clinical outcome in patients with intra-abdominal hollow organ perforations and are associated with perforations in the colorectal tract. Thus, CRP might be a useful marker for preoperative risk stratification and prediction of the localization of the perforation site.

Clinical outcome of patients undergoing abdominoplasty after massive weight loss.

BACKGROUND: Abdominoplasty is one of the most commonly performed surgical procedures to reshape the body contour in patients who have undergone massive weight loss. OBJECTIVES: This study was undertaken to assess the clinical outcome, complication rates, and risk factors for complications of patients undergoing abdominoplasty after massive weight loss. SETTING: University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. METHOD: Clinical outcome was retrospectively analyzed in 121 patients, who underwent abdominoplasty. The retrospective analysis included demographic data of patients, such as sex, age, body mass index (BMI), and pre-existing illnesses. Moreover, postoperative complications including seroma, hematoma, wound infection, and tissue necrosis were analyzed. RESULTS: In our study cohort, the median age was 43.7 years, the median weight was 94.7 kg, and the median BMI was 32.3 kg/m2. The majority of included patients were women (70.3%). Death occurred in none of the patients. Among individuals, wound infection occurred in 3.3%, tissue necrosis in 1.7%, seroma in 7.4%, and hematoma in 3.3% of patients during the postoperative course. Reoperations were necessary in 2 patients (1.7%) due to postoperative bleeding and tissue necrosis of the navel. Tissue necrosis was significantly more often seen in a subset individual with type 2 diabetes (P = .006). Moreover, the rate of reoperations was significantly higher in patients with pre-existing cardiovascular illnesses compared with cardiovascular healthy patients (P = .036). Multivariate analysis analyzing risk factors for postoperative complications, including sex, age, BMI, diabetes, pulmonary disease, and cardiovascular disease, revealed strong independent relevance for type 2 diabetes (P = .024). CONCLUSIONS: We found that abdominoplasty is a safe operative procedure. In addition, the risk for complications is significantly increased in the subgroup of diabetic patients and patients with cardiovascular diseases.

Aberrant expression of Sec61α in esophageal cancers.

INTRODUCTION: The heterotrimeric Sec61α translocon complex is topological located in the membrane of the endoplasmic reticulum (ER) and allows protein transport and calcium across the membrane. Recently, aberrant expression of Sec proteins was linked to carcinogenesis and prognosis of patients. MATERIALS AND METHODS: Here, we analysed the role of Sec61α in esophageal cancer, and we analysed Sec61α staining on a tissue microarray containing more than 600 esophageal cancer specimens by immunohistochemistry. RESULTS: Sec61α staining was always strong in benign esophagus, but was only found in 5% of interpretable esophageal adenocarcinomas (EACs) and 14.5% of squamous cell carcinomas (ESCCs). Reduced Sec61α staining was not strongly linked to tumor phenotype in both subgroups of esophageal cancers and was unrelated to clinical outcome of patients (EACs: p = 0.8051 and ESCCs: p = 0.2751). CONCLUSIONS: Thus, Sec61α measurement has not an additional prognostic benefit for the patients.

High levels of RAI3 expression is linked to shortened survival in esophageal cancer patients.

Expression of the retinoic acid-induced protein 3 (RAI3) has been suggested to predict clinical outcome in a variety of malignancies. However, its role in esophageal cancers remains unclear. Immunohistochemical RAI3 staining was analyzed on tissue microarrays containing 359 esophageal adenocarcinomas (EAC) and 254 esophageal squamous cell carcinomas (ESCC). RAI3 immunostaining was typically absent or weakly detectable in the membranes in benign esophageal tissues. RAI3 staining was higher in malignant than in benign esophagus epithelium. High-levels of RAI3 staining were found in 79.2% of interpretable EACs and 55.9% of ESCCs. In EACs, strong RAI3 staining was associated with advanced pathological tumor stage (p < .0001), high UICC stage (p < .0001), high tumor grade (p = .0133), and positive lymph nodal status (p = .0002). Additionally, high RAI3 staining predicted shortened overall survival of EAC and ESCC patients (p = .0298 and p = .0227). RAI3 overexpression is associated with poor prognosis in esophageal cancers. We propose that RAI3 overexpression might play a biologically relevant role of RAI3 in esophageal cancers.

Prevalence and clinical significance of RBM3 immunostaining in non-small cell lung cancers.

INTRODUCTION: Aberrant expression of RNA-binding motif protein 3 (RBM3) has been suggested as a prognostic biomarker in several malignancies. MATERIALS AND METHODS: This study was performed to analyse the prevalence and clinical significance of RBM3 immunostaining in non-small cell lung cancers (NSCLCs). Therefore, we took advantage of our tissue microarray (TMA) containing more than 600 NSCLC specimens. RESULTS: While nuclear RBM3 staining was always high in normal lung tissue, high RBM3 staining was only seen in 77.1% of 467 interpretable non-metastatic NSCLCs. Reduced RBM3 staining was significantly associated with advanced pathological tumor stage (pT) in NSCLCs (p = 0.0031). Subset analysis revealed that the association between reduced RBM3 staining and advanced pT stage was largely driven by the histological subgroup of lung adenocarcinoma (LUACs) (p = 0.0036). In addition, reduced RBM3 expression predicted shortened survival in LUAC patients (p = 0.0225). CONCLUSIONS: In summary, our study shows that loss of RBM3 expression predicts worse clinical outcome in LUAC patients.

RAI3 is overexpressed in gastric adenocarcinoma but unrelated to prognosis.

PURPOSE: Retinoic acid-induced gene 3 (RAI3) has been associated with tumorigeneses in several cancer types. To clarify the clinical significance of RAI3 expression in premalignant and malignant gastric epithelium, RAI3 protein expression was assessed by immunohistochemistry on tissue microarrays (TMAs) containing 140 gastric dysplasia and 230 GC samples. FINDINGS: RAI3 protein expression was predominantly localized in the cell membrane and was detectable in low intensities in most of the benign gastric tissue samples. RAI3 expression was found in increased intensities in premalignant and malignant epithelium relative to non-malignant gastric epithelium (P < 0.0001). High RAI3 expression was found in 66.2% of interpretable gastric adenocarcinomas and was associated with advanced pathological tumor stage (P = 0.0014) and positive lymph node status (P = 0.0137) but was unrelated to overall survival of patients (P = 0.3743). CONCLUSION: The deregulation of RAI3 in premalignant and gastric epithelium suggests a relevant role of RAI3 during gastric carcinogenesis. Additionally, RAI3 overexpression defines a subset of GCs with aggressive tumor features. However, since RAI3 expression was not associated with clinical outcome of patients, RAI3 cannot be considered as a prognostic biomarker in patients with GCs.

FOXO1 overexpression and loss of pSerine256-FOXO1 expression predicts clinical outcome in esophageal adenocarcinomas.

The function of Forkhead box O 1 (FOXO1) and pSerine256-FOXO1 immunostaining in esophageal cancer is unclear. To clarify the prognostic role of nuclear FOXO1 and cytoplasmic pSerine256-FOXO1 immunostaining, a tissue microarray containing more than 600 esophageal cancers was analyzed. In non-neoplastic esophageal mucosae, FOXO1 expression was detectable in low and pSerine256-FOXO1 expression in high intensities. Increased FOXO1 and decreased pSerine256-FOXO1 expression were linked to advanced tumor stage and high UICC stage in esophageal adenocarcinomas (EACs) (tumor stage: p = 0.0209 and p < 0.0001; UICC stage: p = 0.0201 and p < 0.0001) and squamous cell carcinomas (ESCCs) (tumor stage: p = 0.0003 and p = 0.0016; UICC stage: p = 0.0026 and p = 0.0326). Additionally, overexpression of FOXO1 and loss of pSerine256-FOXO1 expression predicted shortened survival of patients with EACs (p = 0.0003 and p = 0.0133) but were unrelated to outcome in patients with ESCCs (p = 0.7785 and p = 0.8426). In summary, our study shows that overexpression of nuclear FOXO1 and loss of cytoplasmic pSerine256-FOXO1 expression are associated with poor prognosis in patients with EACs. Thus, evaluation of FOXO1 and pSerine256-FOXO1 protein expression - either alone or in combination with other markers - might be useful for prediction of clinical outcome in patients with EAC.

Expression of ICAM-1, E-cadherin, periostin and midkine in metastases of pancreatic ductal adenocarcinomas.

Development and progression of malignant tumors is in part characterized by the ability of a tumor cell to overcome cell-cell and cell-matrix adhesion and to disseminate in organs distinct from that in which they originated. This study was undertaken to analyze the clinical significance of the expression of the following cell-cell and cell-matrix adhesion molecules in pancreatic ductal adenocarcinomas (PDACs) and synchronous liver metastases: intercellular adhesion molecule 1 (ICAM-1), E-cadherin, periostin, and midkine (MK). ICAM-1, E-cadherin, periostin and MK expression was analyzed by immunohistochemistry on a tissue microarray containing 34 PDACs and 12 liver metastasis specimens. ICAM-1 expression was predominantly localized in the membranes of the cells and was found in weak to moderate intensities in PDACs and liver metastases. E-cadherin expression was absent in the majority of PDACs and corresponding liver metastases. The secreted proteins periostin and MK were expressed in various intensities in primary cancers and liver metastases. Statistical analysis demonstrated that the expression levels of the analyzed markers were neither significantly associated with metastasis in PDACs nor with clinical outcome of patients. Our study shows that the expression of the cell-cell and cell-matrix adhesion molecules ICAM-1, E-cadherin, periostin and MK was not significantly linked to metastatic disease in PDACs. Moreover, our study excludes the analyzed markers as prognostic markers in PDACs.

Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer.

DNA mismatch repair (MMR) is integral to the maintenance of genetic stability. We aimed to evaluate the clinical impact of MMR gene expression in prostate cancer. The MMR genes MSH6, MLH1 and PMS2 were analyzed by immunohistochemistry on a tissue microarray containing 11152 prostate cancer specimens. Results were compared with ETS-related gene status and deletions of PTEN, 3p13, 5q21 and 6q15. MSH6, MLH1 and PMS2 expression was detectable in 89.5%, 85.4% and 85.0% of cancers and was particularly strong in cancers with advanced pathological tumor stage (P < 0.0001 each), high Gleason grade (P < 0.0001 each), nodal metastasis (P ≤ 0.0083) and early biochemical recurrence (P < 0.0001). High levels of MMR gene expression paralleled features of genetic instability, such as the number of genomic deletions per cancer; strong expression of all three MMR genes was found in 24%, 29%, 30%, 33% and 42% of cancers with no, one, two, three or four to five deletions (P < 0.0001). The prognostic value of the analyzed MMR genes was largely driven by the subset of cancers lacking ERG fusion (P < 0.0001), while the prognostic impact of MMR gene overexpression was only marginal in ERG-positive cancers. Multivariate analyses suggested an independent prognostic relevance of MMR genes in ERG-negative prostate cancers when compared with prognostic parameters available at the time of initial biopsy. In conclusion, MMR overexpression is common in prostate cancer and is linked to poor outcome as well as features indicating genetic instability. ERG fusion should be analyzed along with MMR gene expression in potential clinical tests.

High Ki67 expression is an independent good prognostic marker in colorectal cancer.

AIMS: To correlate Ki67 expression with outcome in colorectal cancer (CRC). METHODS: Ki67 labelling index (Ki67LI) was analysed by immunohistochemistry on a tissue microarray containing 1800 CRCs. The results were compared with clinicopathological and molecular parameters. RESULTS: Ki67LI was considered low in 26.3%, moderate in 56.7% and high in 17.0% of 1653 interpretable CRCs. High Ki67 expression was associated with low tumour stage (p<0.0001) and nodal status (p=0.0315), but not with tumour grade (p=0.8639), histological tumour type (p=0.1542) or tumour localisation, and was an independent prognosticator of favourable survival (p=0.0121). High Ki67 expression was also significantly associated with high-level nuclear ß-catenin and p53 expression (p<0.0001 and p=0.0095, respectively). CONCLUSIONS: In summary, our data show that high Ki67 expression in CRCs is associated with good clinical outcome. Ki67, p53 and ß-catenin overexpression seem to be linked to CRC, and indicate a cellular state of high proliferative activity. Finally, our findings strongly argue for a clinical utility of Ki67 immunostaining as an independent prognostic biomarker in CRC.