Several pathohistological classification systems exist for the diagnosis of gastric cancer. Many studies have investigated the correlation between the pathohistological characteristics in gastric cancer and patient characteristics, disease specific criteria and overall outcome. It is still controversial as to which classification system imparts the most reliable information, and therefore, the choice of system may vary in clinical routine. In addition to the most common classification systems, such as the Laurén and the World Health Organization (WHO) classifications, other authors have tried to characterize and classify gastric cancer based on the microscopic morphology and in reference to the clinical outcome of the patients. In more than 50 years of systematic classification of the pathohistological characteristics of gastric cancer, there is no sole classification system that is consistently used worldwide in diagnostics and research. However, several national guidelines for the treatment of gastric cancer refer to the Laurén or the WHO classifications regarding therapeutic decision-making, which underlines the importance of a reliable classification system for gastric cancer. The latest results from gastric cancer studies indicate that it might be useful to integrate DNA- and RNA-based features of gastric cancer into the classification systems to establish prognostic relevance. This article reviews the diagnostic relevance and the prognostic value of different pathohistological classification systems in gastric cancer.

BackgroundHistorical data indicate that surgical resection may benefit select patients with metastatic gastric and gastroesophageal junction cancer. However, randomized clinical trials are lacking. The current RENAISSANCE trial addresses the potential benefits of surgical intervention in gastric and gastroesophageal junction cancer with limited metastases.MethodsThis is a prospective, multicenter, randomized, investigator-initiated phase III trial. Previously untreated patients with limited metastatic stage (retroperitoneal lymph node metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) receive 4 cycles of FLOT chemotherapy alone or with trastuzumab if Her2+. Patients without disease progression after 4 cycles are randomized 1:1 to receive additional chemotherapy cycles or surgical resection of primary and metastases followed by subsequent chemotherapy. 271 patients are to be allocated to the trial, of which at least 176 patients will proceed to randomization. The primary endpoint is overall survival; main secondary endpoints are quality of life assessed by EORTC-QLQ-C30 questionnaire, progression free survival and surgical morbidity and mortality. Recruitment has already started; currently (Feb 2017) 22 patients have been enrolled.DiscussionIf the RENAISSANCE concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, patients with gastric or GEJ cancer and metastases will no longer be considered candidates for surgical intervention.Trial registrationThe article reports of a health care intervention on human participants and is registered on October 12, 2015 under ClinicalTrials.gov Identifier: NCT02578368; EudraCT: 2014–002665-30.

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Purpose: High expression of cyclooxygenase-2 (COX-2) was shown to inhibit chemotherapyand radiotherapy-induced apoptosis. We analyzed the association of COX-2 mRNA and protein expression with histomorphologic response to neoadjuvant radiochemotherapy in esophageal cancer. Experimental Design: Fifty-two patients with resectable esophageal cancers (cT2-4, N x , and M 0 ) received neoadjuvant radiochemotherapy (cisplatin, 5-5-fluorouracil, 36 Gy) followed by transthoracic en bloc esophagectomy. Histomorphologic regression was defined as major response when resected specimens contained less than 10% of residual vital tumor cells. RNA was isolated from endoscopic biopsies (paired tumor and normal tissue) before neoadjuvant treatment and quantitative real-time reverse transcriptase-PCR (Taqman) assays were done to determine COX-2 mRNA expression levels standardized for h-actin. COX-2 protein expression in pretreatment biopsies and post-therapeutic resection specimens was analyzed by immunostaining of tumor cells.Results: Median COX-2 mRNA expression levels were significantly (P < 0.0001) different between paired tumor (median, 2.2) and normal tissues (median, 0.159). Comparison of pretherapeutic and posttherapeutic specimens showed a significant difference (P < 0.006) in COX-2 protein expression. Twelve of 52 tumors showed down-regulation and 3 of 52 showed up-regulation of COX-2 protein expression during neoadjuvant radiochemotherapy. High COX-2 protein expression in post-therapeutic resection specimens was significantly associated with minor histopathologic response (P < 0.04) and poor prognosis (5-year survival probabilities: 26.3 F 8.2% for minor and 58.6% F 12.9% for major histopathologic response; P < 0.01).Conclusion: High COX-2 protein expression following neoadjuvant radiochemotherapy in resection specimens is significantly associated with minor histopathologic response to neoadjuvant therapy and very poor prognosis.

The aim of this prospective study was to analyze Ming's classification in correlation with other currently used classification systems of gastric cancer. In addition, we wanted to define the prognostic significance of the Ming classification system. The present study analyzed material of 117 patients with gastric carcinoma who underwent D2-gastrectomy with curative intent. All specimens were categorized according to International Union Against Cancer (UICC) classification, World Health Organization (WHO) classification, Borrmann classification, Laurén classification, Goseki classification, Ming classification, and tumor differentiation. For analysis of correlation between the classification systems, the correlation coefficient according to Spearman was calculated. The survival curves have been calculated according to the Kaplan-Meier method. According to the Ming classification, 38.5% of the carcinomas exhibited an expanding growth pattern, and 61.5% of specimens showed an infiltrating growth pattern. The subtypes according to the Ming and Laurén classification correlated significantly (P < 0.001). WHO classification (P < 0.001), tumor differentiation (P < 0.001), and Goseki classification (P < 0.001), as well as the macroscopic classification of Borrmann (P < 0.001) and the pT and pN categories of the UICC classification exhibited a highly significant correlation with the Ming classification (P < 0.001 and 0.001, respectively). Median overall survival was 31.3 months. In Kaplan-Meier analysis, the 3-year survival rates were lower in the infiltrative tumor type when compared to the expansive tumor type according to Ming (P = 0.0847). In multivariate analysis, only the UICC system presented as an independent prognostic factor in multivariate analysis (P < 0.001). This study shows that the Ming classification correlates significantly with the currently used classification systems for gastric cancer and with the UICC staging system, especially, the pT and pN category. The 3-year survival rates were lower in the infiltrative tumor type than in the expansive tumor type according to Ming. However, the Ming classification is not an independent prognostic factor.