Union Against Cancer Research Articles

Issues and inconsistencies in the revised gynecologic staging systems

In addition to acting as diagnosticians, surgical pathologists are increasingly becoming prognosticians. Currently there are 3 staging groups: the International Federation of Gynecology and Obstetrics (FIGO), the American Joint Commission on Cancer (AJCC), and the International Union against Cancer (UICC), each forming its own staging system. However, despite diligent efforts, these classification systems do not yet agree in their reporting of cancer staging. Because having a uniform set of staging guidelines is essential for consistent interpretation and management of patients with cancer, we attempt to review the issues and inconsistencies that exist in the current staging guidelines. Specifically, we compare and contrast the AJCC/UICC and the parallel system formulated by FIGO in the diagnosis of cancers in the gynecologic tract, focusing on the vulva, vagina, cervix, and endometrium/uterus. Our hopes are to clarify the controversies, because a more unified system must be created to eliminate ongoing inconsistencies, and to make communication and treatment even more reliable.

Perihilar cholangiocarcinoma: a surgeon’s viewpoint on current topics

Perihilar cholangiocarcinomas are defined anatomically as "tumors that are located in the extrahepatic biliary tree proximal to the origin of the cystic duct". However, as the boundary between the extrahepatic and intrahepatic bile ducts is not well defined, perihilar cholangiocarcinomas potentially include two types of tumors: one is the "extrahepatic" type, which arises from the large hilar bile duct, and the other is the "intrahepatic" type, which has an intrahepatic component with the invasion of the hepatic hilus. The new TNM staging system published by the International Union Against Cancer (UICC) has been well revised with regard to perihilar cholangiocarcinoma, but it still lacks stratification of patient prognosis and has little applicability for assessing the feasibility of surgical treatment; therefore, further refinement is essential. Most patients with perihilar cholangiocarcinomas present with jaundice, and preoperative biliary drainage is mandatory. Previously, percutaneous transhepatic biliary drainage was used in many centers; however, it is accepted that endoscopic naso-biliary drainage is the most suitable method of preoperative drainage. Portal vein embolization is now widely used as a presurgical treatment for patients undergoing an extended hepatectomy to minimize postoperative liver dysfunction. The surgical resection of a perihilar cholangiocarcinoma is technically demanding and continues to be the most difficult challenge for hepatobiliary surgeons. Because of advances in diagnostic and surgical techniques, surgical outcomes and survival rates after resection have steadily improved. However, survival, especially for patients with lymph node metastasis, is still unsatisfactory, and the establishment of adjuvant chemotherapy is necessary. Further synergy of endoscopists, radiologists, oncologists, and surgeons is required to conquer this intractable disease.

Chirurgie des Magenkarzinoms in einer Schwerpunktklinik

The aim of the study was to evaluate prognostic factors for the surgical treatment of gastric cancer in a medium volume center. The investigation focused in particular on morbidity and mortality. From January 2005 to August 2011 a total of 74 patients with gastric cancer were surgically treated in our medium volume center. The study of these patients included morbidity, mortality, UICC (International Union Against Cancer) stage, Laurén classification, surgical therapy procedure, American Society of Anesthesiologists (ASA) classification and duration of surgery. After surgery 11 patients suffered from complications with a morbidity of 14.9% and a mortality of 1.4% (n=1). No significant differences could be detected during the study period. In comparison to other studies the morbidity and mortality rates signify similar to better data than complications of high volume centers which might be due to the small group of surgeons who are specialized in gastric surgery.

Upstaging of early colorectal cancers following improved lymph node yield after methylene blue injection

To evaluate whether the use of intra-arterial methylene blue injection improves lymph node yield, and to determine whether a higher lymph node count results in upstaging in colorectal cancer. We performed a retrospective study of colorectal cancer specimens (n = 234) 1 year after implementation of the method. All colorectal cancer specimens from the previous year served as our control group. Data concerning tumour characteristics, lymph node count, number of positive lymph nodes and success of methylene injection had been prospectively collected in accordance with the department's ongoing registration. The method was easy to implement and perform with a high rate of success (86%). The number of identified lymph nodes was highly significantly improved in the study group (P < 0.0001). In resections with pT1/T2 tumours, we demonstrated a significant increase in the number of resection specimens containing positive lymph nodes, with an increase in pN1 resections from 9.4% in the control group to 26.7% in the study group (P = 0.04). THE methylene blue technique significantly improves lymph node identification in colorectal cancer specimens, and the improved lymph node identification leads to upstaging of International Union Against Cancer (UICC) pT1/pT2 cancers.

Osteoporosis Self-assessment Tool for Asians as a simple risk index of identifying a poor prognosis in women surgically treated for colorectal cancer

BackgroundOsteoporosis and colorectal cancer (CRC) in older women are considered enormous public health burdens. The effects of osteoporosis on the oncologic outcome of CRC surgery are poorly understood. We evaluated the use of the Osteoporosis Self-assessment Tool for Asians (OSTA) for predicting postoperative outcome in older women after receiving surgical treatment of CRC. Materials and methodsThe present single-institution retrospective study analyzed patients who had undergone surgery for CRC in 2002–2008. To characterize the major population of women with osteoporosis, which consists of postmenopausal women, only patients aged 50 years and older were analyzed. Their OSTA scores were evaluated for correlations with cancer-specific survival after surgery for CRC by performing univariate, multivariate, and survival analyses. ResultsDuring a 7-year period, 440 women were studied. The cancer-specific mortality and overall mortality rate was 28.4% and 33.4%, respectively. The univariate analyses revealed that significant predictors of cancer-specific mortality after CRC surgery were the International Union Against Cancer (UICC) stage, OSTA category, histologic grading, lymph node metastases, and tumor invasion depth. After risk adjustment, the UICC stage and OSTA risk index were independent predictors of mortality. A comparison of OSTA risk index among patients with different UICC stages showed that the accuracy of the index in predicting cancer-specific survival after CRC surgery was greatest for patients with stage II and III disease. ConclusionsThe UICC stage and OSTA risk status showed independent positive associations with postoperative mortality in aged female patients with CRC. Moreover, the OSTA index had a particularly strong association with cancer-specific mortality in patients with UICC stage II and III.

Enrichment of CD133‐expressing cells in rectal cancers treated with preoperative radiochemotherapy is an independent marker for metastasis and survival

The transmembrane glycoprotein CD133 (cluster of differentiation 133; also known as Prominin or PROM1) has been described as a potential stem cell marker in colorectal cancer and is associated with higher tumorigenic potential and resistance to radiochemotherapy (RCT). In this study, CD133 expression was evaluated in pre-RCT tumor biopsies and the corresponding post-RCT surgical specimens from patients with locally advanced rectal adenocarcinoma, and expression levels were correlated with histopathologic features and clinical follow-up. One hundred twenty-six patients with International Union Against Cancer (UICC) stage II/III rectal cancer who received preoperative 5-fluorouracil (5-FU)-based RCT within the German Rectal Cancer Trials were investigated. Pre-RCT and post-RCT CD133 expression levels were determined using immunohistochemistry and were correlated with histopathologic parameters, tumor regression grade, cancer recurrence, and patient survival. Compared with pre-RCT biopsies, significantly higher CD133 expression was observed in tumor specimens (P = .01). However, no correlations were observed for either biopsies or tumor specimens between CD133 expression levels, histopathologic characteristics, or survival. In matched analyses of corresponding biopsy/tumor pairs, patients who had an increased fraction of CD133-expressing (CD133+) cells after preoperative RCT had significantly higher residual tumor stages (P = .02) and lower histopathologic tumor regression (P < .01). Moreover, these patients had significantly reduced disease-free survival and cancer-specific overall survival in univariate analysis (P < .001 and P = .004, respectively) and multivariate analysis (P = .003 and P = .024, respectively). The enrichment of CD133+ cancer cells during preoperative RCT was correlated with minor local tumor response, increased distant cancer recurrence, and decreased survival. The current results indicate that the up-regulation of intratumoral CD133 expression, in contrast to absolute pre-RCT and post-RCT CD133 levels, plays an important role in tumor progression and metastasis in patients with rectal cancer who are receiving neoadjuvant RCT.

Can the new RCP R0/R1 classification predict the clinical outcome in ductal adenocarcinoma of the pancreatic head?

According to the International Union Against Cancer (UICC), R1 is defined as the microscopic presence of tumor cells at the surface of the resection margin (RM). In contrast, the Royal College of Pathologists (RCP) suggested to declare R1 already when tumor cells are found within 1mm of the RM. The aim of this study was to determine the significance of the RM concerning the prognosis of pancreatic ductal adenocarcinoma (PDAC). From 2007 to 2009, 62 patients underwent a curative operation for PDAC of the pancreatic head. The relevance of R status on cumulative overall survival (OS) was assessed on univariate and multivariate analysis for both the classic R classification (UICC) and the suggestion of the RCP. Following the UICC criteria, a positive RM was detected in 8%. Along with grading and lymph node ratio, R status revealed a significant impact on OS on univariate and multivariate analysis. Applying the suggestion of the RCP, R1 rate rose to 26% resulting in no significant impact on OS in univariate analysis. Our study has shown that the RCP suggestion for R status has no impact on the prognosis of PDAC. In contrast, our data confirmed the UICC R classification of RM as well as N category, grading, and lymph node ratio as significant prognostic factors.

Analysis of survival prediction value using modification 7th UICC esophageal cancer staging system for esophageal squamous cell carcinoma with preoperative radiotherapy

Objective To evaluate the value of the international union against cancer (UICC)stage,pathologic complete response (pCR),and the estimated treatment response as various means for prognostic stratifying patients after surgery in patients with squamous cell carcinoma of the esophagus who received preoperative radiotherapy (RT).Methods A retrospective review was performed on 311 patients with esophageal squamous cell carcinoma who received RT before the esophagectomy. Data collected included the demographics,the RT details,the pathologic findings,and the survival.Prognostic survival was analyzed by Kaplan-Meier method and Logrank test.Results The follow-up rate was 96.5％,89 and 43 patients,respectively were followed up more than 5 and 10 years.In univariate analysis,residual disease and the number of positive lymph node were predictors of the overall survival ( T-pCR,x2 =11.53,P =0.001 ;0,1 -3,≥4,x2=42.13,P=0.000,respectively).Further study found the 7th stage system of UICC cannot (can or cannot) entirely predict the prognosis of this group of patients.If categorizing the stages of their lymph nodes into three groups:N0(0),N1 (1-3) and N2(≥4)),and the modified UICC system can accurately distinguish ypStage Ⅰ with ypStage Ⅱ ( T0.3 N 1 M0 + T3 N0 M0 ) ( x2 =11.15,P =0.001 ) and ypStage Ⅱ with ypStage Ⅲ ( T4 N0-1 M0 and T0-3 N2 M0 ) ( x2 =23.39,P =0.000 ).Conclusions The pathologic post-radiotherapy T stage and the number of positive lymph node are predictors for esophageal squamous cell carcinoma receiving preoperative radiotherapy.The modified UICC stage system can be a better survival predictor than the 7th UICC stage system. Key words: Esophageal neoplasms/preoperative radiotherapy; Modified international union against cancer stage; Prediction prognosis

Accuracy of the current TNM classification in predicting survival in patients with sinonasal mucosal melanoma

The first International Union Against Cancer (UICC) TNM classification for aerodigestive malignant mucosal melanoma was not published until 2009, and since then, only a few studies have evaluated the accuracy of this staging system. Our aim was to evaluate the accuracy of this UICC staging system for sinonasal malignant mucosal melanoma (SMMM) in a nationwide survey. Retrospective, population-based, multicenter study. The hospital surgical and discharge registries were used to identify the patients. A database including demographic and clinicopathologic variable was created. Altogether, 50 SMMM patients diagnosed in Finland from 1990 to 2004 were evaluated. Three- and 5-year overall survival rates were 44% and 27%, respectively. Significant differences in overall survival according to T classification (P = .028, log rank) and stage (P = .02, log rank) were found. Tumor extension to the sphenoid sinus had a significant negative impact on survival (n = 11, P = .03, log rank). The current UICC staging system for mucosal melanoma provides a useful format for staging SMMMs in clinical settings.

Tumour budding: a promising parameter in colorectal cancer.

In 2011, the Tumour Node Metastasis (TNM) staging system still remains the gold standard for stratifying colorectal cancer (CRC) patients into prognostic subgroups, and is considered a solid basis for treatment management. Nevertheless, there is still a challenge with regard to therapeutic strategy; stage II patients are not typically selected for postoperative adjuvant chemotherapy, although some stage II patients have a comparable outcome to stage III patients who, themselves do receive such treatment. Consequently, there has been an inundation of ‘prognostic biomarker’ studies aiming to improve the prognostic stratification power of the TNM staging system. Most proposed biomarkers are not implemented because of lack of reproducibility, validation and standardisation. This problem can be partially resolved by following the REMARK guidelines. In search of novel prognostic factors for patients with CRC, one might glance at a table in the book entitled ‘Prognostic Factors in Cancer’ published by the International Union against Cancer (UICC) in 2006, in which TNM stage, L and V classifications are considered ‘essential’ prognostic factors, whereas tumour grade, perineural invasion, tumour budding and tumour-border configuration among others are proposed as ‘additional’ prognostic factors. Histopathology reports normally include the ‘essential’ features and are accompanied by tumour grade, histological subtype and information on perineural invasion, but interestingly, the tumour-border configuration (i.e., growth pattern) and especially tumour budding are rarely reported. Although scoring systems such as the ‘BRE’ in breast and ‘Gleason’ in prostate cancer are solidly based on histomorphological features and used in daily practice, no such additional scoring system to complement TNM staging is available for CRC. Regardless of differences in study design and methods for tumour-budding assessment, the prognostic power of tumour budding has been confirmed by dozens of study groups worldwide, suggesting that tumour budding may be a valuable candidate for inclusion into a future prognostic scoring system for CRC. This mini-review therefore attempts to present a short and concise overview on tumour budding, including morphological, molecular and prognostic aspects underlining its inter-disciplinary relevance.

The Prognostic Value of Tumor-Infiltrating Neutrophils in Gastric Adenocarcinoma after Resection

BackgroundSeveral pieces of evidence indicate that tumor-infiltrating neutrophils (TINs) are correlated to tumor progression. In the current study, we explore the relationship between TINs and clinicopathological features of gastric adenocarcinoma patients. Furthermore, we investigated the prognostic value of TINs.Patients and MethodsThe study was comprised of two groups, training group (115 patients) and test group (97 patients). Biomarkers (intratumoral CD15+ neutrophils) were assessed by immunohistochemistry. The relationship between clinicopathological features and patient outcome were evaluated using Cox regression and Kaplan-Meier analysis.ResultsImmunohistochemical detection showed that the tumor-infiltrating neutrophils (TINs) in the training group ranged from 0.00–115.70 cells/high-power microscopic field (HPF) and the median number was 21.60 cells/HPF. Based on the median number, the patients were divided into high and low TINs groups. Chi-square test analysis revealed that the density of CD15+ TINs was positively associated with lymph node metastasis (p = 0.024), distance metastasis (p = 0.004) and UICC (International Union Against Cancer) staging (p = 0.028). Kaplan-Meier analysis showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.002). Multivariate Cox's analysis showed that the density of CD15+ TINs was an independent prognostic factor for overall survival of gastric adenocarcinoma patients. Using another 97 patients as a test group and basing on the median number of TINs (21.60 cells/HPF) coming from the training group, Kaplan-Meier analysis also showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.032). The results verify that the number of CD15+ TINs can predict the survival of gastric adenocarcinoma surgical patients.ConclusionsThe presence of CD15+ TINs is an independent and unfavorable factor in the prognosis of gastric adenocarcinoma patients. Targeting CD15+ TINs may be a potential intervenient therapy in the future.

Prohibitin in squamous cell carcinoma of the lung: its expression and possible clinical significance

rohibitin is localized to mitochondria where it might have a role in the maintenance of mitochondrial function and protection against senescence. In this study, we show that prohibitin is up-regulated in lung squamous cell carcinoma tissues compared with adjacent normal tissues using agarose 2-dimensional differential gel electrophoresis and immunoblotting. Prohibitin expression was further evaluated by immunohistochemistry. We statistically analyzed the association of prohibitin expression with clinicopathologic indicators in 78 patients with lung squamous cell carcinoma. Our data suggested that prohibitin expression was positively correlated with the International Union Against Cancer (UICC) classification of tumor grade (P < .001), pathologic stage (P < .001), tumor size (P = .01), and lymph node metastasis (P = .004). Furthermore, we found that prohibitin expression was an independent prognostic indicator (P = .037) for overall survival of patients with lung squamous cell carcinoma by multivariate analysis using the Cox regression method. These findings may encourage further studies investigating prohibitin function in lung squamous cell carcinoma.

An Attempt at Validation of the Seventh Edition of the Classification by the International Union Against Cancer for Esophageal Carcinoma

The aim of our study was to investigate the ability of the Seventh edition of the classification by the International Union Against Cancer (UICC) to identify patients at higher risk and to predict the overall survival in patients with esophageal carcinoma. Demographic and clinical data of 605 patients, who underwent esophagectomy for esophageal carcinoma between 1992 and 2009, were analyzed. Tumor stage and grade were classified according to the sixth and seventh editions of the UICC classification. Tumor depth (T), lymph node affection (N), and metastasis (M) status according to the seventh edition of the UICC classification showed significant differences in survival of each single status. Kaplan-Meier analysis of overall survival by the seventh edition of the UICC classification showed poor discrimination between stages Ib and IIa (p=0.098), stages IIIa and IIIb (p=0.672), and stages IIIc and IV (p=0.799). Further, the estimated median survival time between stages IIa and IIb was discordant. The seventh edition of the UICC TNM classification cannot satisfactorily distinguish among different risk groups of patients with resected esophageal carcinoma. The new subgroups do not unify the different TNM stages with similar survival. We strongly propose that the next revision of the UICC classification should reduce the stages to groups with similar survival, without defining complex subgroups.

Adjuvant chemotherapy with gemcitabine and S‐1 after surgical resection for advanced biliary carcinoma: outcomes and prognostic factors

The aims of this study were to evaluate long-term outcomes and to determine prognostic factors for survival in patients with resected biliary carcinoma who received adjuvant gemcitabine plus S-1 chemotherapy. Seventy patients with International Union Against Cancer (UICC) stage II, III, or IV biliary carcinoma received postoperative adjuvant chemotherapy consisting of intravenous gemcitabine 700 mg/m(2) on day 1 and oral S-1 60-100 mg/body for seven consecutive days, followed by a 1-week pause of chemotherapy. Patients received up to ten 2-week cycles. Long-term outcomes and predictors of survival with this adjuvant chemotherapy regimen were analyzed. The median duration of follow-up was 47 months. Fifty-six percent of patients had node-positive disease, and 80% of patients underwent R0 resection. Overall and disease-free survival rates were 91 and 81% at 1 year, 56 and 55% at 3 years, and 40 and 46% at 5 years, respectively. Lymph node status (p = 0.025) and surgical margin status (p = 0.033) were independently associated with long-term survival by multivariate analysis. Adjuvant gemcitabine plus S-1 chemotherapy may be a promising strategy for patients with resected biliary carcinoma, and nodal status and surgical margin status may be predictors of survival with this treatment strategy.

Endocrine carcinoma of the stomach: clinicopathological analysis of 27 surgically treated cases in a single institute

Gastric endocrine carcinoma (EC) is an uncommon tumor of the stomach and the clinical features are not well known. Additionally, the classification and staging systems of this tumor are not yet unified worldwide. In this study, we reviewed 27 patients with gastric EC to evaluate the clinicopathological characteristics of this tumor. We retrospectively reviewed 27 patients with gastric EC among 6466 patients who had undergone gastrectomy between 1986 and 2008 at our institute. Clinicopathological features including immunohistochemistry of Ki-67 were investigated to evaluate the malignant potential of the tumor. Furthermore, survivals were compared between the 7th edition of the International Union Against Cancer (UICC)-TNM (7th TNM) classification for gastric cancer (GC) and the new TNM classification for foregut neuroendocrine tumors (NET). The median survival of the patients was 19.0 months. The 5-year survival rate was 100% in pathological stage (pStage) I, 40% in pStage II, 38% in pStage III, and 11% in pStage IV according to the 7th TNM classification for GC. Survivals by stage showed great difference between the 7th TNM classification for GC and the new TNM classification for foregut NET, but each system correlated with survival. The Ki-67 labeling index was more than 20% in most of the patients. Univariate analysis revealed that maximum tumor diameter, tumor depth, lymph node metastasis, lymphatic invasion, pStage, and curability had significant correlations with survival. Early detection and curative operations are essential for improving the prognosis of gastric EC. However, some adjuvant chemotherapies are required for advanced-stage tumors. Classification and staging systems may need to be unified worldwide for further analysis.

Does Colorectal Cancer in Ulcerative Colitis Patients Constitute a Risk for Chemotherapy Refractoriness? A Systemic Approach by Detailed Analysis via the Electronic Tumor Base Documentation System

Background: Ulcerative colitis (UC) patients may develop colorectal cancer (CRC), especially with pancolitis and longer UC duration. The question whether CRC with underlying UC has a dismal prognosis remains unsettled. Patients and Methods: We performed an electronic tumor base documentation (eTBD) search of CRC and UC patients at our department to address whether (1) CRC prognosis is impaired and (2) defined risks can be determined. Results: With the inclusion of an index patient with UC and unresponsive CRC, 20 additional patients were identified via eTBD. Chemotherapy response was less substantial, with complete response or stable disease in 3 patients each, but rapidly progressing or refractory disease in 15/21 patients. 12 out of the 21 patients died. Our hazard ratio analysis revealed International Union against Cancer (UICC) stage IV and III disease, grade 3 tumors, longer latency from UC to CRC and age >60 years as potential risks. Median progression-free survival and overall survival were 48 and 82 months, respectively. Time from tumor dissemination to death was 10 months. Conclusions: The prognosis of CRC in UC patients is not necessarily impaired, albeit chemotherapy response with disseminated disease may be unfavorable. Our data should be enlarged by subsequent analyses to better elucidate whether response in UC and CRC is more challenging and defined risks can be confirmed.

Die neue TNM-Klassifikation der Tumoren des ösophagogastralen Übergangs

The new International Union Against Cancer (UICC) classification in its seventh version has been out since January 2010. It included some important changes for the classification of esophageal and gastric carcinomas compared to the sixth version. For esophageal carcinomas this means a more detailed subdivision of the T and N stages which should, together with the newly introduced prognostic grouping (separate for squamous cell carcinoma and adenocarcinoma) enable a more precise and individualized prediction of prognosis. Another innovation is that positive lymph nodes in the esophageal drainage area, including celiac axis nodes and paraesophageal lymph nodes in the neck, are classified as regional lymph node metastases rather than distant metastatic spread, irrespective of tumor location. Hereby the lymphadenectomy specimen should include ≥ 6 lymph nodes (LN). The most controversial improvement is that adenocarcinomas of the esophagogastric junction (AEG) are all classified as esophageal carcinomas. This should acknowledge the similar prognosis of AEGs and esophageal carcinomas, which is worse compared to gastric carcinomas in other locations. Regarding the classification of gastric carcinomas the T-stages were redefined and lymph node staging (N-stage) was refined to allow for a better prediction of prognosis. The lymphadenectomy specimen after gastrectomy should hereby include ≥ 16 LNs. As the primary aim of the UICC classification is a preferably accurate prognosis prediction, the impact on a surgeon's therapeutic decision is low. For decisions regarding the type of resection the endoscopic AEG classification with the aim of R0 resections is still the instrument of choice. The value of the UICC classification is that it enables sophisticated comparisons between different treatment regimens and strategies.

Enhanced Activity of Meprin-α, a Pro-Migratory and Pro-Angiogenic Protease, in Colorectal Cancer

Meprin-α is a metalloprotease overexpressed in cancer cells, leading to the accumulation of this protease in a subset of colorectal tumors. The impact of increased meprin-α levels on tumor progression is not known. We investigated the effect of this protease on cell migration and angiogenesis in vitro and studied the expression of meprin-α mRNA, protein and proteolytic activity in primary tumors at progressive stages and in liver metastases of patients with colorectal cancer, as well as inhibitory activity towards meprin-α in sera of cancer patient as compared to healthy controls. We found that the hepatocyte growth factor (HGF)- induced migratory response of meprin-transfected epithelial cells was increased compared to wild-type cells in the presence of plasminogen, and that the angiogenic response in organ-cultured rat aortic explants was enhanced in the presence of exogenous human meprin-α. In patients, meprin-α mRNA was expressed in colonic adenomas, primary tumors UICC (International Union Against Cancer) stage I, II, III and IV, as well as in liver metastases. In contrast, the corresponding protein accumulated only in primary tumors and liver metastases, but not in adenomas. However, liver metastases lacked meprin-α activity despite increased expression of the corresponding protein, which correlated with inefficient zymogen activation. Sera from cancer patients exhibited reduced meprin-α inhibition compared to healthy controls. In conclusion, meprin-α activity is regulated differently in primary tumors and metastases, leading to high proteolytic activity in primary tumors and low activity in liver metastases. By virtue of its pro-migratory and pro-angiogenic activity, meprin-α may promote tumor progression in colorectal cancer.

Correct Evaluation of the 7th Edition of the TNM Classification for Gastric Cancer?

TO THE EDITOR: We read with great interest the article by Warneke et al, which reported that the seventh edition of the International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC) TNM classification for gastric cancer has not improved the assessment of patient prognosis compared with the fifth and sixth editions of the UICC/AJCC TNM classification. In contrast, other investigators demonstrated that the seventh edition of the TNM classification for gastric cancer was more suitable for predicting the prognosis of patients after surgery than the previous editions. After a careful analysis of this article’s results, we found several obvious defects which could give rise to bias in the conclusions and which should be addressed in detail. In comparison with patients with gastric cancer, patients with esophagogastric junction tumors could have a more distinctive prognosis, given that these patients were classified as having esophageal cancer according to the seventh edition of the UICC/AJCC TNM classification. In addition, the authors did not provide detailed information to show the number of dissected lymph nodes, which is considered a requirement for curative resection of gastric cancer and radical lymphadenectomy. Actually, 15 or more lymph nodes should be required to determine the accurate pN stage and inhibit stage migration. Lastly, we found that some patients described in this article as having advanced stage cancer only underwent palliative resection and had distant metastasis. These patients must have had a poorer prognosis and could not be evaluated precisely for TNM classification. Strictly speaking, patients with distant metastasis should be excluded from the study.

Overexpression of minichromosome maintenance 2 predicts poor prognosis in patients with gastric cancer

We examined the expression of minichromosome maintenance 2 (MCM2) in gastric cancer and adjacent normal tissues and estimated the possible value of MCM2 as a novel prognostic marker. Using real-time PCR, western blotting and immunohistochemistry, we examined the expression of MCM2 in gastric carcinoma and paired normal gastric mucosa. Statistical analysis of the expression of MCM2 mRNA and protein in gastric cancer and normal tissues was performed to evaluate the relationship between MCM2 expression and clinicopathological characteristics in gastric cancer. The expression of MCM2 mRNA and protein in gastric carcinomas was significantly higher compared to that in normal gastric mucosa (P=0.04). Immunohistochemistry analysis showed that MCM2 expression was significantly up-regulated in tumor and metastastic lymph node tissues compared with the corresponding non-cancerous mucosa (P<0.05). Positive expression of MCM2 was significantly associated with patient age, T category and the presence of lymph node metastasis (P<0.05). There were no differences between MCM2 expression and gender, tumor size, tumor location, M category, International Union Against Cancer (UICC) stage, vessel invasion and tumor differentiation. Patients with negative tumor MCM2 expression displayed a better survival time than those with positive MCM2 expression (P<0.05). Survival analysis showed that positive MCM2 expression (P<0.05), T stage (P<0.05) and N stage (P<0.05) were independent prognostic factors for disease-free survival (DFS) and overall survival (OS). Our data suggest that MCM2 could serve as a novel prognostic biomarker in gastric carcinoma.