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Neoadjuvant immunochemotherapy (NAIC) achieves superior clinical benefits over neoadjuvant chemotherapy (NAC) in multiple types of human cancers, including gastric adenocarcinoma (GAC). However, it is poorly understood how the malignant epithelial cells and tumor immune microenvironment (TIME) might respond distinctly to NAIC and NAC that underlies therapeutic efficacy. Here treatment‐naive and paired tumor tissues from multiple centers were subjected to pathological, immunological, and transcriptomic analysis. NAIC demonstrated significantly increased rate of pathological complete response compared to NAC (pCR: 25% vs. 4%, p < 0.05). Interestingly, pretreatment intestinal subtype of Lauren's classification was predictive of pathologic regression following NAIC, but not NAC. A substantial portion of cancers underwent intestinal‐to‐diffuse transition, which occurred less following NAIC and correlated with treatment failure. Moreover, NAIC prevented reprogramming to an immunosuppressive TIME with less active fibroblasts and exhausted CD8+ T cells, and increased numbers of mature tertiary lymphoid structures. Mechanistically, activation of the tumor necrosis factor alpha (TNFα)/nuclear factor‐kappa B (NF‐κB) signaling pathway was associated with response to NAIC. Together, NAIC is superior to NAC for locally advanced GAC, likely due to reduced intestinal‐to‐diffuse conversion and reprogramming to an immuno‐active TIME. Modulation of the histological conversion and immunosuppressive TIME could be translatable approaches to improve neoadjuvant therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Abstract Neoadjuvant immunochemotherapy (NAIC) achieves superior clinical benefits over neoadjuvant chemotherapy (NAC) in multiple types of human cancers, including gastric adenocarcinoma (GAC). However, it is poorly understood how the malignant epithelial cells and tumor immune microenvironment (TIME) might respond distinctly to NAIC and NAC that underlies therapeutic efficacy. Here treatment‐naive and paired tumor tissues from multiple centers were subjected to pathological, immunological, and transcriptomic analysis. NAIC demonstrated significantly increased rate of pathological complete response compared to NAC (pCR: 25% vs. 4%, p

Introduction: The management of gastric cancer in advanced stages, which is the second most leading cause of cancer mortality in the world, has evolved very little. Surgical resection remains the mainstay of treatment and can cure patients with early-stage cancer. The survival rate of patients with advanced resectable-gastric cancers, however, remains poor despite new treatment strategies. A better understanding of the molecular basis of cancer has contributed to the development of rationally designed molecular targeted therapies, which interfere with the signalling cascades involved in cell differentiation, proliferation and survival. Aim: To evaluate the expression of HER2 (Human epidermal growth factor receptor 2) by Immunohistochemistry (IHC) in intestinal and diffuse type gastric carcinomas, in and around Kanchipuram, Tamil Nadu, India. Materials and Methods: Fifty cases (31 males, 19 females) were selected which includes 30 cases of resected gastric carcinoma specimens and 20 cases of endoscopic guided biopsies diagnosed as gastric carcinoma in the Department of Pathology, in Meenakshi Medical College and Research Institute (MAHER), Enathur, Kanchipuram, Tamil Nadu which is a teaching medical college and hospital in southern part ofIndia from January 2012 to July 2014 for a period of two and half years. All the cases that were received during the study period that-fulfilled the inclusion and exclusion criteria were included in the study. All cases were analysed for their expression of HER 2/Neu protein antigen by Immunohistochemical staining in this study. The scoring criteria established by an international consensus panel of oncologists and pathologists was followed. Breast carcinoma tissue positively expressing HER2 was used as the positive control. We considered only those tumours expressing 3+positivity as those expressing HER2. Results: HER2 score was significantly higher in intestinal type gastric carcinomas. Of the total 26 cases expressing the HER2 protein, 81% (21/26) were of intestinal type Vs 19% (5/26) that of diffuse types (p=0.007). Also, no statistical difference was found between other variables like age and gender (p=0.098 and p=0.985). Conclusion: This study assessed the expression of HER2 in gastric carcinomas and we found a statistically significant expression in intestinal type gastric carcinomas than the diffuse type gastric carcinomas. There was no significant overexpression of HER2 protein regarding the clinicopathological variables like age and gender.

Introduction: The management of gastric cancer in advanced stages, which is the second most leading cause of cancer mortality in the world, has evolved very little. Surgical resection remains the mainstay of treatment and can cure patients with early-stage cancer. The survival rate of patients with advanced resectable-gastric cancers, however, remains poor despite new treatment strategies. A better understanding of the molecular basis of cancer has contributed to the development of rationally designed molecular targeted therapies, which interfere with the signalling cascades involved in cell differentiation, proliferation and survival. Aim: To evaluate the expression of HER2 (Human epidermal growth factor receptor 2) by Immunohistochemistry (IHC) in intestinal and diffuse type gastric carcinomas, in and around Kanchipuram, Tamil Nadu, India. Materials and Methods: Fifty cases (31 males, 19 females) were selected which includes 30 cases of resected gastric carcinoma specimens and 20 cases of endoscopic guided biopsies diagnosed as gastric carcinoma in the Department of Pathology, in Meenakshi Medical College and Research Institute (MAHER), Enathur, Kanchipuram, Tamil Nadu which is a teaching medical college and hospital in southern part of-India from January 2012 to July 2014 for a period of two and half years. All the cases that were received during the study period that-fulfilled the inclusion and exclusion criteria were included in the study. All cases were analysed for their expression of HER 2/Neu protein antigen by Immunohistochemical staining in this study. The scoring criteria established by an international consensus panel of oncologists and pathologists was followed. Breast carcinoma tissue positively expressing HER2 was used as the positive control. We considered only those tumours expressing 3+positivity as those expressing HER2. Results: HER2 score was significantly higher in intestinal type gastric carcinomas. Of the total 26 cases expressing the HER2 protein, 81% (21/26) were of intestinal type Vs 19% (5/26) that of diffuse types (p=0.007). Also, no statistical difference was found between other variables like age and gender (p=0.098 and p=0.985). Conclusion: This study assessed the expression of HER2 in gastric carcinomas and we found a statistically significant expression in intestinal type gastric carcinomas than the diffuse type gastric carcinomas. There was no significant overexpression of HER2 protein regarding the clinicopathological variables like age and gender. [ABSTRACT FROM AUTHOR]

Background: The clinicopathological features of mixed-type (MT) early gastric cancer (EGC) according to Lauren's classification remain uninvestigated. This study aimed to clarify the clinicopathological features of MT EGC, particularly in relation to lymph node metastasis (LNM) and long-term survival.Methods: This study included 5309 patients who underwent gastrectomy for EGC. The clinicopathological features, LNM, and long-term outcomes of patients with MT carcinomas were compared with those of patients with intestinal-type (IT) and diffuse-type (DT) cancers. Furthermore, we evaluated the predictors of LNM in each Lauren classification subgroup.Results: Patients with MT carcinomas were likelier to have larger tumors, submucosal invasion, lymphovascular invasion, and LNM than those with IT or DT carcinomas. Multivariate logistic regression analysis revealed that the Lauren classification was a significant predictor of LNM (P < 0.001). The significant predictors of LNM in MT carcinomas were female sex, greater tumor size, presence of submucosal invasion, and lymphovascular invasion. However, the overall survival of patients with MT carcinoma was not significantly different from that of patients with IT or DT carcinomas (P = 0.104).Conclusions: The presence of MT EGC carries a higher risk of LNM compared with the presence of IT or DT carcinomas. Therefore, MT carcinomas should be managed with gastrectomy that includes lymph node dissection instead of endoscopic resection. [ABSTRACT FROM AUTHOR]

Foi selecionada uma amostra aleatória (334 indivíduos) de todos os pacientes diagnosticados com câncer de estômago no período de 1980 a 1995 no Instituto Nacional do Câncer, Rio de Janeiro, sendo revisados seus dados histopatológicos. A concordância entre os diagnósticos prévios e atuais quanto à Classificação de Lauren foi considerada substancial (kappa= 0,65). Baseando-se nesta classificação, observou-se um declínio estatisticamente não significativo das proporções de câncer gástrico de tipo intestinal em idosos (sessenta anos ou mais) de ambos os sexos (em homens, 41,0% no período de 1980-1985, 37,9% de 1986 a 1990 e 28,8% de 1991 a 1995; entre mulheres, as proporções foram, respectivamente de 41,4%, 31,5% e 15,2%). As proporções de câncer gástrico de tipo intestinal permaneceram relativamente estáveis para os pacientes menores de sessenta anos.This study draws a random sample (334 individuals) of all patients diagnosed with stomach cancer from 1980 to 1995 at the National Cancer Institute in Rio de Janeiro, Brazil, and reviews histopathological data. Agreement between previous and present classification of the histopathological material (Laurén's classification) was considered quite substantial (kappa = 0.65). Based on this classification, a statistically nonsignificant trend towards decline in the intestinal type of stomach cancer among older individuals (60 years old or older) from both genders was observed (males: 41.0% in 1980-1985, 37.9% in 1986-1990, and 28.8% in 1991-1995; females: 41.4%, 31.5%, and 15.2%, respectively). Proportions of the intestinal type among younger patients from both genders remained stable throughout the period.

A clinicopathological study of gastric carcinoma was carried out according to Lauren's classification, on 207 patients, who underwent gastric resection at Department of Surgery II, Kyushu University, Faculty of Medicine from 1970 to 1972. Among them 93 cases (44.9%) were of intestinal-type carcinoma, 71 (34.3%) of diffuse carcinoma and 43 (20.8%) of other types. Intestinal-type carcinoma, often showing the protuberant type, was more common in the aged and in men. Most had a low grade of penetration, while in some, the penetration was moderate to high grade and was associated with lymph node metastasis, lymphatic and vascular involvement, or liver metastasis. Hematogenous recurrence was not infrequent. Diffuse carcinoma was more common in younger subjects and women, and was often of the depressed type. The serosa was involved in most cases. High grade penetration was associated with lymphatic permeation. Metastasis via the bloodstream was infrequent. Recurrence was often due to peritoneal dissemination. A better prognosis was indicated in cases of diffuse carcinoma with no serosal involvement, while prognosis in cases of invasion of the serosa was worse for diffuse carcinoma than for intestinal-type carcinoma. [ABSTRACT FROM AUTHOR]

Gastric carcinomas are divided into two types according to Lauren's classification: intestinal and diffuse types. Polyamines (putrescine, spermidine, and spermine) are polycations involved in neoplastic growth of gastrointestinal mucosa. A key role is also played by ornithine decarboxylase, the rate limiting enzyme in polyamine metabolism. Our aim was to investigate whether there were differences between the two types of tumor in polyamine metabolism. Twenty-seven patients with gastric carcinoma entered the study. Seventeen carcinomas were classified as diffuse type and 10 as intestinal type. Polyamine levels were evaluated by high-performance liquid chromatography. Ornithine decarboxylase activity was measured by a radiometric technique. Polyamine levels and ornithine decarboxylase activity were significantly higher in intestinal type samples than diffuse type samples. A similarity of polyamine levels in intestinal type samples with levels previously observed in patients with colorectal adenocarcinoma was also found. These findings show a different proliferative behavior of these two types of tumor, and therefore different therapeutic strategies can be hypothesized. [ABSTRACT FROM AUTHOR]

Background: Our study aims to analyze the association between Lauren's classification and gastric adenocarcinoma prognosis using comprehensive statistical analyses., Methods: According to the selection criteria, patients were included from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression, propensity score matching, and a multivariate competing risk model were used to investigate the association between Lauren's classification and prognosis. Subgroup analysis was used to investigate the role of confounding factors on the association between Lauren types and prognosis., Results: After exclusion, a total of 20,218 patients from the SEER database were included, with 14,374 intestinal types and 5,844 diffuse types. The univariate Cox regression analysis revealed that the diffuse type had a poorer cancer-specific survival (CSS) rate [hazard ratio (HR), 1.44; 95% confidence interval (CI), 1.38-1.50]. After adjusting for confounding variables, the diffuse type also showed a higher risk of cancer-specific death (HR, 1.20; 95% CI, 1.15-1.20). Sensitivity analysis showed that after propensity score matching, the diffuse type had a poorer CSS rate (HR, 1.23; 95% CI, 1.10-1.36), and the competing risk model further validated these results [subdistribution HR (SHR), 1.32; 95% CI, 1.23-1.41]. Moreover, subgroup analysis demonstrated stable results in the subgroups, except for patients with T1 stage (HR, 1.06; 95% CI, 0.87-1.28) and a tumor size <2 cm (HR, 1.00; 95% CI, 0.83-1.21)., Conclusions: Diffuse-type gastric adenocarcinoma had an overall poorer prognosis compared to the intestinal type. However, in patients with T1 stage and tumor size <2 cm, the diffuse type had a comparable survival rate with the intestinal type., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-7953). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Foi selecionada uma amostra aleatória (334 indivíduos) de todos os pacientes diagnosticados com câncer de estômago no período de 1980 a 1995 no Instituto Nacional do Câncer, Rio de Janeiro, sendo revisados seus dados histopatológicos. A concordância entre os diagnósticos prévios e atuais quanto à Classificação de Lauren foi considerada substancial (kappa= 0,65). Baseando-se nesta classificação, observou-se um declínio estatisticamente não significativo das proporções de câncer gástrico de tipo intestinal em idosos (sessenta anos ou mais) de ambos os sexos (em homens, 41,0% no período de 1980-1985, 37,9% de 1986 a 1990 e 28,8% de 1991 a 1995; entre mulheres, as proporções foram, respectivamente de 41,4%, 31,5% e 15,2%). As proporções de câncer gástrico de tipo intestinal permaneceram relativamente estáveis para os pacientes menores de sessenta anos.