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      Mixed Carcinoma as an Independent Prognostic Factor in Submucosal Invasive Gastric Carcinoma

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          Abstract

          Mixed carcinoma shows a mixture of glandular and signet ring/poorly cohesive cellular histological components and the prognostic significance of each component is not fully understood. This study aimed to investigate the significance of the poorly cohesive cellular histological component as a risk factor for lymph node metastasis and to examine the diagnostic reliability of endoscopic biopsy. Clinicopathologic characteristics of 202 patients who underwent submucosal invasive gastric carcinoma resection with lymph node dissection in 2005–2012 were reviewed. Mixed carcinoma accounted for 27.2% (56/202) of cases. The overall prevalence of lymph node metastasis was 17.3% (35/202). Lymphatic invasion ( P < 0.001), family history of carcinoma ( P = 0.025), tumor size ( P = 0.004), Lauren classification ( P = 0.042), and presence of any poorly cohesive cellular histological component ( P = 0.021) positively correlated with the lymph node metastasis rate on univariate analysis. Multivariate analyses revealed lymphatic invasion, family history of any carcinoma, and the presence of any poorly cohesive cellular histological component to be significant and independent factors related to lymph node metastasis. Review of preoperative biopsy slides showed that preoperative biopsy demonstrated a sensitivity of 63.6% and a specificity of 100% in detecting the presence of the poorly cohesive cellular histological component, compared with gastrectomy specimens. The presence of any poorly cohesive cellular histological component was an independent risk factor associated with lymph node metastasis in submucosal invasive gastric carcinoma. Endoscopic biopsy had limited value in predicting the presence and proportion of the poorly cohesive cellular histologic component due to the heterogeneity of mixed carcinoma.

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          Most cited references26

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          Clinical Practice Guidelines for Gastric Cancer in Korea: An Evidence-Based Approach

          Although gastric cancer is quite common in Korea, the treatment outcome is relatively favorable compared to those in western countries. However, there are currently no Korean multidisciplinary guidelines for gastric cancer. Experts from related societies developed guidelines de novo to meet Korean circumstances and requirements, including 23 recommendation statements for diagnosis (n=9) and treatment (n=14) based on relevant key questions. The quality of the evidence was rated according to the GRADE evidence evaluation framework: the evidence levels were based on a systematic review of the literature, and the recommendation grades were classified as either strong or weak. The applicability of the guidelines was considered to meet patients' view and preferences in the context of Korea. The topics of the guidelines cover diagnostic modalities (endoscopy, endoscopic ultrasound, and radiologic diagnosis), treatment modalities (surgery, therapeutic endoscopy, chemotherapy, and radiotherapy), and pathologic evaluation. An external review of the guidelines was conducted during the finalization phase.
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            Endoscopic mucosal resection and endoscopic submucosal dissection.

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              Mixed-type gastric carcinomas exhibit more aggressive features and indicate the histogenesis of carcinomas

              To investigate the pathobiological behaviors of gastric mixed-type (MT) carcinomas and gastric carcinogenesis, the clinicopathological characteristics of MT carcinomas were analyzed and compared with intestinal-type (IT) and diffuse-type (DT) carcinomas. The expression of Ki-67, caspase-3, p53, fragile histine triad (FHIT), maspin, extracellular matrix metalloproteinase inducer (EMMPRIN), vascular growth factor (VEGF), MUC-2, 4, 5AC and 6, CD44, E-cadherin, β-catenin, and phosphorylated glycogen synthase kinase 3β-ser9 (P-GSK3β-ser9) was examined on tissue microarrays using immunohistochemistry. It was found that MT carcinomas exhibited large size, deep invasion, frequent local invasion, and lymph node metastasis in comparison with IT and DT carcinomas (p < 0.05). All the markers except MUC-5AC showed higher expression in IT than DT carcinomas (p < 0.05). The expression of maspin, EMMPRIN, VEGF, MUC-4, and membrane E-cadherin was stronger in MT intestinal than diffuse component (p < 0.05). Immunoreactivities to Ki-67, EMMPRIN, and VEGF were weaker in IT carcinoma than in the MT intestinal portion (p < 0.05), while the opposite was true for CD44, MUC-2, and MUC-6 (p < 0.05). The MT diffuse component displayed a higher expression of FHIT, VEGF, and P-GSK3β-ser9 than DT carcinoma (p < 0.05). The accumulative survival rate of the IT carcinoma patients was higher than the other types (p < 0.05). The invasive depth, venous invasion, lymph node, peritoneal or liver metastasis, and Lauren's classification were independent prognostic factors for gastric carcinomas (p < 0.05). These findings suggested that MT carcinomas were also indicated to be more aggressive than IT and DT carcinomas. Significant differences were observed in the proliferation, apoptosis, angiogenesis, mucin secretion, and cell adhesion between IT and DT carcinomas, whereas only a few of these characteristics showed differences between the MT intestinal and diffuse parts, thus suggesting that both the MT components might originate from the stem cells with similar genetic traits, but follow different histogenic pathways.
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                Author and article information

                Journal
                J Korean Med Sci
                J. Korean Med. Sci
                JKMS
                Journal of Korean Medical Science
                The Korean Academy of Medical Sciences
                1011-8934
                1598-6357
                June 2016
                11 April 2016
                : 31
                : 6
                : 866-872
                Affiliations
                [1 ]Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
                [2 ]Department of Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.
                Author notes
                Address for Correspondence: Hye Seung Han, MD. Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 05030, Korea. 20040002@ 123456kuh.ac.kr
                Author information
                http://orcid.org/0000-0002-5972-3516
                http://orcid.org/0000-0002-5288-8772
                http://orcid.org/0000-0003-0346-9042
                http://orcid.org/0000-0002-3602-9257
                http://orcid.org/0000-0002-3591-9995
                Article
                10.3346/jkms.2016.31.6.866
                4853664
                27247494
                51daf293-eb33-4f95-a4eb-61f2b12f61b0
                © 2016 The Korean Academy of Medical Sciences.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 October 2015
                : 09 March 2016
                Categories
                Original Article
                Oncology & Hematology

                Medicine
                early gastric cancer,lymph node metastasis,biopsy,mixed carcinoma,gastrointestinal endoscopy

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