High-Resolution Diffusion-Weighted Imaging for Evaluation of Extramural Tumor Invasion in Primary Rectal Cancer.

OBJECTIVE: The aim of this study was to determine the added value of high-resolution diffusion-weighted imaging (DWI) to T2-weighted imaging (T2WI) for evaluation of extramural tumor invasion (EMTI) in patients with primary rectal cancer. METHODS: Seventy-eight patients who had undergone 3.0-T magnetic resonance imaging including DWI (b = 0, 1000 s/mm2, 2 mm iso-voxel) and subsequent surgery were included. Two blinded radiologists independently read the T2WI first and then the combined DWI set. They recorded their confidence level using a 5-point scale. The diagnostic accuracy was calculated by receiver operating characteristic curve analysis based on the histopathological results as the reference. RESULTS: The study population consisted of EMTI positive (n = 44) and negative (n = 34). The area under the curve was not significantly increased after adding DWI to T2WI (reader 1, 0.868-0.856, P = 0.5618; reader 2, 0.848-0.865, P = 0.4539). CONCLUSION: Adding DWI to T2WI showed no additional diagnostic value for the evaluation of EMTI in patients with primary rectal cancer.

Systemic inflammation is associated with the density of immune cells in the tumor microenvironment of gastric cancer.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) and the prognostic nutritional index (PNI) are markers of systemic inflammation known to be useful prognostic indicators of malignancy. However, little evidence has defined the influence of inflammation on the tumor microenvironment. METHODS: Two hundred eighty-eight patients who underwent curative surgery for gastric cancer were included. Preoperative peripheral blood samples were used to analyze the NLR and PNI. The optimal cutoff levels for the NLR and PNI were defined by receiver operating characteristic curve analysis for survival (NLR = 2.7, PNI = 47.7). The densities of specific immune cells (CD3+, CD4+, CD8+) within the tumor microenvironment were measured in tumor microarrays by immunohistochemical analysis. RESULTS: Two hundred thirty-five patients (81.6 %) had a low NLR and 53 patients (18.4 %) had a high NLR. One hundred seventeen patients (40.6 %) had a low PNI and 171 patients (59.4 %) had a high PNI. CD3+ and CD8+ immune cell density were not associated with the NLR and PNI. However, in the high-NLR group compared with the low-NLR group, CD4+ immune cell density was significantly decreased (P < 0.001). Similarly, the density of CD4+ immune cells was also significantly decreased in the low-PNI group compared with the high-PNI group (P = 0.007). A high NLR and a low PNI were correlated with worse overall survival in multivariate analysis (P = 0.028 and P = 0.002 respectively). CONCLUSIONS: The NLR and PNI are associated with the density of CD4+ immune cells in the tumor microenvironment, which leads to prognostic values of systemic inflammation in gastric cancer.

Multifocal Kaposiform Hemangioendothelioma Causing Massive Fetal Chylous Ascites.

Kaposiform hemangioendothelioma (KHE) is a locally aggressive vascular tumor that usually occurs in soft tissues of the extremity and rarely in the retroperitoneum. We report a unique case of isolated massive fetal ascites attributed to KHE, involving the retroperitoneum and multiple visceral organs, along with the Kasabach-Merritt phenomenon. We suspect that retroperitoneal KHE might have caused massive fetal ascites because of its high potential to invade the lymphatic vessels aggressively in the retroperitoneal space, which possibly permits intestinal lymph leakage into the peritoneal cavities.

Favorable prognosis in colorectal cancer patients with co-expression of c-MYC and ß-catenin.

BACKGROUND: The purpose of our research was to determine the prognostic impact and clinicopathological feature of c-MYC and ß-catenin overexpression in colorectal cancer (CRC) patients. METHODS: Using immunohistochemistry (IHC), we measured the c-MYC and ß-catenin expression in 367 consecutive CRC patients retrospectively (cohort 1). Also, c-MYC expression was measured by mRNA in situ hybridization. Moreover, to analyze regional heterogeneity, three sites of CRC including the primary, distant and lymph node metastasis were evaluated in 176 advanced CRC patients (cohort 2). RESULTS: In cohort 1, c-MYC protein and mRNA overexpression and ß-catenin nuclear expression were found in 201 (54.8 %), 241 (65.7 %) and 221 (60.2 %) of 367 patients, respectively, each of which was associated with improved prognosis (P = 0.011, P = 0.012 and P = 0.033, respectively). Moreover, co-expression of c-MYC and ß-catenin was significantly correlated with longer survival by univariate (P = 0.012) and multivariate (P = 0.048) studies. Overexpression of c-MYC protein was associated with mRNA overexpression (ρ, 0.479; P < 0.001) and nuclear ß-catenin expression (ρ, 0.282; P < 0.001). Expression of c-MYC and ß-catenin was heterogeneous depending on location in advanced CRC patients (cohort 2). Nevertheless, both c-MYC and ß-catenin expression in primary cancer were significantly correlated with improved survival in univariate (P = 0.001) and multivariate (P = 0.002) analyses. c-MYC and ß-catenin expression of lymph node or distant metastatic tumor was not significantly correlated with patients' prognosis (P > 0.05). CONCLUSIONS: Co-expression of c-MYC and ß-catenin was independently correlated with favorable prognosis in CRC patient. We concluded that the expression of c-MYC and ß-catenin might be useful predicting indicator of CRC patient's prognosis.

Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer.

BACKGROUND: There are few data on the clinical implications of immunosuppressive protein expression in tumors and immune cell infiltration within the tumor microenvironment in patients with gastric cancer (GC). METHODS: In this study, 243 patients with curatively resected GC were included. The levels of immunosuppressive protein expression [programmed cell death 1 ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO)] in tumors and the densities of immune cells [CD3(+), CD4(+), CD8(+), or PD-1(+) cells] within the tumor microenvironment were measured using immunohistochemical analysis. RESULTS: Positive PD-L1, CTLA-4, and IDO expression was observed in 43.6, 65.8, and 47.7% of the patients, respectively. Expression of PD-L1, CTLA-4, and IDO was related to less advanced stage, intestinal type, and well/moderately differentiated adenocarcinoma (P < 0.05). PD-L1 expression was related to better disease-free survival (DFS) and overall survival (OS) in GC [PD-L1(+) vs. PD-L1(-) tumors: 5-year DFS rate, 82.6 vs. 66.9%; 5-year OS rate, 83.0 vs. 69.1% (P values <0.05)]. Survival outcomes were also better in patients with a higher density of CD3(+) cells within the tumor microenvironment than in those with a lower density of CD3(+) cells [5-year DFS rate, 80.9 vs. 67.0%; 5-year OS rate, 82.5 vs. 68.0% (P values <0.05)]. In multivariate analysis, these two immune markers had a prognostic impact on survival, independent of other clinical variables. CONCLUSIONS: GC patients with immunosuppressive protein expression (PD-L1, CTLA-4, or IDO) had distinct clinicopathological characteristics. PD-L1(+) expression and a high-CD3 tumor microenvironment are favorable prognostic markers in GC.

Deregulation of the cell polarity protein Lethal giant larvae 2 (Lgl2) correlates with gastric cancer progression.

BACKGROUND: We investigated the roles of Lethal giant larvae 2 (Lgl2), an epithelial cell polarity protein, during gastric carcinogenesis and gastric cancer (GC) progression and evaluated the correlation of Lgl2 with epithelial-mesenchymal transition (EMT) markers. METHODS: Lgl2 protein and mRNA expression were determined by immunohistochemistry and mRNA in situ hybridization in a large series of GC and preneoplastic lesions. Additionally, expression of 7 EMT markers was examined by immunohistochemistry. RESULTS: Loss of membrane Lgl2 staining in GC was observed in 347 of 409 GCs. Lgl2 loss was associated with diffuse histological type (P < 0.001), advanced stage (P = 0.021), and worse prognosis (P = 0.047). Furthermore, Lgl2 loss correlated with reduced E-cadherin expression (P < 0.01) and increased expression of vimentin (P < 0.01). Combined analysis of Lgl2 and the EMT markers, S100A4 and MMP2, improved predictions of patient outcomes. During gastric carcinogenesis, membrane expression of Lgl2 was progressively lost in 4 % of normal mucosa, 75 % of intestinal metaplasia, 58 % of gastric dysplasia, 69 % of intestinal type GC, and 96 % of diffuse type GC. CONCLUSIONS: Our results suggest that Lgl2 loss occurs at an early stage of gastric carcinogenesis and contributes to GC progression.

The quantification of HER2 and MYC gene fragments in cell-free plasma as putative biomarkers for gastric cancer diagnosis.

BACKGROUND: This study aimed to investigate the significance of circulating HER2 and MYC gene fragments quantification in the diagnosis of gastric cancer. METHODS: Levels of HER2 and MYC genes were evaluated by fluorescence in situ hybridization and real-time PCR in 81 gastric cancer tissues, and by real-time PCR in 36 gastritis tissues. Real-time PCR for HER2 and MYC products was also performed on 184 plasma samples from 81 gastric cancers, eight gastric adenomas, 63 gastritis patients, and 32 healthy individuals. RESULTS: HER2/HBB and MYC/HBB ratios in tissue and cell-free plasma from gastric cancer patients were significantly higher than those of gastritis tissue and cancer-free individuals. An optimized cut-off value of plasma target gene to HBB ratio, used to differentiate cancer patients from cancer-free individuals, was evaluated using receiver operating characteristic (ROC) curves. Values of 2.0 were calculated for HER2 [area under the ROC curve (AUC), 0.760] and 2.725 for MYC (AUC, 0.767). A combination model of HER2 and MYC provided a better differentiation condition than that for HER2 or MYC only (AUC, 0.850). HER2/HBB ratios in plasma from gastric cancer patients correlated with MYC/HBB ratios. CONCLUSIONS: Our findings suggest that the measurement of plasma HER2 and MYC gene levels could improve the screening of gastric cancer.

Caveolin 1 expression correlates with poor prognosis and focal adhesion kinase expression in gastric cancer.

OBJECTIVE: Caveolin 1 gene is known as a tumor promoter or suppressor, depending on the tumor type and/or tumor stage. We aimed to investigate the clinical significance of caveolin 1 protein (Cav1) expression in gastric cancer (GC). METHODS: Immunohistochemistry was performed on tissue array slides containing 405 GC specimens. The relationships between Cav1 expression and clinicopathological factors, prognosis, focal adhesion kinase expression, mucin phenotypes and p53 expression were analyzed. RESULTS: In non-neoplastic gastric mucosa, Cav1 was not expressed in the epithelial compartment. In GC, positive staining of Cav1 was shown in 22 (5.4%) of 405 cases and was significantly higher in the advanced GC group than in the early GC group (p = 0.037). Also, it was significantly associated with advanced pTNM stage (p = 0.027) and lymph node metastasis (p = 0.018). Moreover, survival analysis showed that Cav1 expression was an independent prognostic factor of poor survival (p = 0.028). In addition, the expression of Cav1 was positively correlated with that of focal adhesion kinase (p = 0.034). CONCLUSIONS: These results indicate that the expression of Cav1 is significantly correlated with cancer progression and poor prognosis in GC. Thus, Cav1 could supplement its protein expression for the diagnosis and treatment of GC.

Association between Dynamic Contrast-Enhanced MRI Parameters and Prognostic Factors in Patients with Primary Rectal Cancer.

BACKGROUND: To evaluate the association between perfusion parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with prognostic factors in primary rectal cancer patients. METHODS: A sample of 51 patients with pathologically proven rectal adenocarcinoma through surgery were retrospectively enrolled. All the patients underwent preoperative DCE-MRI including 3D-spoiled gradient echo. Two radiologists determined the tumor border after radiologic-pathologic correlation and drew regions of interest. The perfusion parameters, including the volume transfer constant (Ktrans), were calculated under the extended Toft model. The prognostic factors included TN stage, circumferential resection margin, extramural venous invasion, Kirsten-ras mutation, tumor size, carcinoembryonic antigen, and tumor differentiation. The association was assessed via correlation or t-test. For significant prognostic factors, receiver operating characteristic (ROC) curve analyses were performed to estimate the diagnostic predictive values. RESULTS: Ktrans only showed a significant difference according to tumor differentiation, between the well-differentiated (n = 6) and moderately differentiated (n = 45) groups (0.127 ± 0.032, 0.084 ± 0.036, p = 0.036). The AUC was 0.838 (95% CI, 0.702-0.929), and the estimated accuracy, sensitivity, and specificity were 87%, 90%, and 60%, respectively. CONCLUSIONS: Ktrans showed a significant difference based on tumor differentiation, which may be conducive to prediction of prognosis in primary rectal cancer.

Development and Validation of Models to Predict Lymph Node Metastasis in Early Gastric Cancer Using Logistic Regression and Gradient Boosting Machine Methods.

PURPOSE: To identify important features of lymph node metastasis (LNM) and develop a prediction model for early gastric cancer (EGC) using a gradient boosting machine (GBM) method. MATERIALS AND METHODS: The clinicopathologic data of 2556 patients with EGC who underwent gastrectomy were used as training set and the internal validation set (set 1) at a ratio of 8:2. Additionally, 548 patients with EGC who underwent endoscopic submucosal dissection (ESD) as the initial treatment were included in the external validation set (set 2). The GBM model was constructed, and its performance was compared with that of the Japanese guidelines. RESULTS: LNM was identified in 12.6% (321/2556) of the gastrectomy group (training set & set 1) and 4.3% (24/548) of the ESD group (set 2). In the GBM analysis, the top five features that most affected LNM were lymphovascular invasion, depth, differentiation, size, and location. The accuracy, sensitivity, specificity, and the area under the receiver operating characteristics of set 1 were 0.566, 0.922, 0.516, and 0.867, while those of set 2 were 0.810, 0.958, 0.803, and 0.944, respectively. When the sensitivity of GBM was adjusted to that of Japanese guidelines (beyond the expanded criteria in set 1 [0.922] and eCuraC-2 in set 2 [0.958]), the specificities of GBM in sets 1 and 2 were 0.516 (95% confidence interval, 0.502-0.523) and 0.803 (0.795-0.805), while those of the Japanese guidelines were 0.502 (0.488-0.509) and 0.788 (0.780-0.790), respectively. CONCLUSION: The GBM model showed good performance comparable with the eCura system in predicting LNM risk in EGCs.

A Huge Malignant Gastric Gastrointestinal Stromal Tumor in a Young Patient.

Malignant gastrointestinal stromal tumors (GISTs) are rare neoplasms originating from the gastrointestinal tract that rarely occur in patients below 40 years of age. To our knowledge, there have been no previous reports of satellite and metastatic nodules in GIST. We present a case of a young patient with a huge malignant gastric GIST accompanied by spontaneous bleeding and satellite and metastatic nodules, successfully treated surgically, without preoperative chemotherapy administration. A 28-year-old man was admitted to Haeundae Paik Hospital with melena. A huge bulging gastric mass with ulceration and bleeding was observed on endoscopy. A subepithelial lesion on the stomach body, abutting the pancreatic body and tail, with regional lymph node enlargement was confirmed by EUS and CT. Radical total gastrectomy was performed, the invasion surrounding the pancreatic tail and spleen were surgically dissected, and enlarged lymph nodes around the celiac trunk and the common hepatic artery were removed. The pathology results showed a malignant GIST with two satellite nodules and a metastatic tumor nodule at the left paracardial lymph node site. After complete resection of the malignant GIST, adjuvant chemotherapy with imatinib was initiated. Follow-up CT and endoscopy performed 6 months after surgery confirmed no recurrence of the disease.

Gastric Malignant Peripheral Nerve Sheath Tumor in Type 1 Neurofibromatosis.

Gastric malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare spindle cell sarcomas that arise within the peripheral nerves of the gastrointestinal tract. MPNST can present as a mass that may or may not be accompanied by obstruction or bleeding. Type 1 neurofibromatosis (NF) is an autosomal dominant genetic disorder with an incidence of 1 in 2,500-3,000. Plexiform neurofibromas in Type 1 NF can undergo a malignant transformation to MPNSTs. Approximately half of the incidence of MPNST is associated with the NF-1 gene. MPNST behaves aggressively, and radical excisional surgery is important for treatment. Recurrence and metastasis are significant, even after a radical excision. Despite multidisciplinary treatment, the five-year survival rate is only 30-50%. This paper reports the case of a 47-year-old man with Type 1 NF who presented with hemorrhage of a gastric subepithelial lesion. He underwent surgery under the suspicion of a gastrointestinal stromal tumor, but it was diagnosed as MPNST after confirming the histopathological appearance and immunohistochemical profiles. In addition, the large mass invaded the spleen and diaphragm. Radical surgery was performed, and additional chemotherapy was administered. This paper reports the experience of a patient with NF 1 with advanced MPNST discovered due to a subepithelial lesion.

Costal Osteoma: Report of a Case in an Unusual Site.

BACKGROUND Osteoma is a benign bone tumor that typically arises in facial bones and less frequently in the long bones. It rarely occurs in the appendiceal skeleton. Pathologic findings are similar to those for parosteal osteosarcoma, periostitis ossificans, and osteoid osteoma. Diagnosing osteoma at an unusual site is always problematic. Here, we present a case of costal osteoma that was found incidentally on screening and produced mild symptoms in the patient. CASE REPORT A 53-year-old man was examined because of a rib mass in the eighth rib on his left side, which had been present for 2 years. A computed tomography scan revealed that the intensely dense mass arose from the external surface of the eighth rib. Microscopic examination showed that the lesion consisted of mature lamellar bone with several Haversian systems, typical of an osteoma. No atypical spindle cells or necrosis were identified. The diagnosis was osteoma. CONCLUSIONS Because the anatomy of the ribs poses a challenge when performing needle biopsy, diagnosing bony lesions solely based on that technique is difficult. The diagnosis of costal osteoma should be made carefully, based on clinical, radiological, and pathological findings. To the best of our knowledge, ours is the first case report about a costal osteoma. It is useful for chest surgeons, pathologists, and radiologists as an example of a rare presentation of this tumor.

Primary Mature Teratoma of the Rectum: A Case Report.

BACKGROUND Teratomas are embryonal neoplasms that contain tissues derived from 1 or more of the 3 germ layers. They commonly are found in the sacrococcygeal-gonadal location, sometimes in midline locations such as the mediastinum, retroperitoneum, and head and neck region. Primary rectal teratomas are extremely rare. Extragonadal teratomas can originate from pluripotent germ cells present in abnormal embryonic rests. CASE REPORT Here, we report a rare case of a primary mature, solid teratoma of the rectum. A 68-year-old woman presented with hematochezia and denied any history of abdominal pain or a change in bowel habits. Colonoscopy revealed a 4-cm pedunculated polyp in the rectum. No hair was present on its surface. The polyp was completely removed by polypectomy. Histologically, the tumor consisted of mature components from all 3 germ layers. Its surface was covered by squamous epithelium with hair follicles and sweat glands. Adipose tissue, blood vessels, bone, and glandular epithelium were present inside the mass. No evidence was found of immature elements or malignant features. CONCLUSIONS When polypoid lesions are found in the rectum, teratoma should be considered in the differential diagnosis. Histopathological confirmation is necessary to diagnose teratoma. Primary rectal teratomas should be distinguished from other neoplastic polyps as well as from local spread of teratomas arising in adjacent organs. These neoplasms are usually mature (benign) but may undergo malignant transformation. Therefore, complete resection is recommended to alleviate symptoms and avoid the risk of malignancy.

Multiple small bowel metastasis of primary non-small cell lung cancer.

Gastrointestinal metastasis could be considered in the differential diagnosis of melena in the patient with NSCLC history.

Rapid destruction of shoulder joint by pigmented villonodular synovitis treated by hemiarthroplasty: A case report.

INTRODUCTION: Pigmented villous nodular synovitis is an uncommon proliferative disease of the joints, and rarely reported in the shoulder. It can become symptomatic when proliferating soft tissue infiltrates a joint, causing arthritic changes including bone erosion. The literature has described the disease progression as indolent. Here we report on a case of PVNS of the shoulder joint which rapidly lead to significant bone damage and was subsequently treated by shoulder arthroplasty. PRESENTATION OF CASE: We report here on a 71-year old female patient who presented with a 6 month history of aggravating shoulder pain. Radiography imaging over a one month period indicated rapid joint destruction. Magnetic resonance imaging suggested the presence of PVNS of the shoulder joint and significant bone erosion. The patient was subsequently treated by shoulder arthroplasty performed by authors. Histological examination confirmed the PVNS diagnosis. Shoulder pain significantly decreased during the follow up period, and the patient was able to resume daily activities. DISCUSSION: Comparing to Milwaukee shoulder syndrome or a joint infection, PVNS is known to progress indolently. However, our case clearly showed that PVNS could also cause radical destruction of the joint. Previous reports showed the high recurrence rate of PVNS after joint preserving surgery. In our experience hemiarthroplasty could be the choice of treatment with the low recurrence rate and high functional outcome. CONCLUSIONS: Physicians should include PVNS in the differential diagnosis when they are presented with evidence of rapid destruction of the shoulder joint. Hemiarthroplasty could be treatment option for PVNS of shoulder joint.

Recurrent Primary Pleomorphic Liposarcoma of the Breast: A Case Report with Imaging Findings.

Primary pleomorphic liposarcoma of the breast is rare, and only a few cases in the literature have reported imaging findings. Herein, we report a rare case of primary pleomorphic liposarcoma of the breast in a 38-year-old woman and describe the imaging findings including mammography, ultrasonography, computed tomography, magnetic resonance imaging, and 18F-Fluorodeoxyglucose-positron emission tomography. Although most fat-containing breast masses are benign, malignancy can occur. Magnetic resonance imaging can be helpful for further evaluation of breast masses.

Gastric Adenocarcinoma Arising from Heterotopic Pancreas Presenting as Gastric Outlet Obstruction 10 Years after the First Diagnosis.

Gastric heterotopic pancreas is a relatively uncommon incidental finding. On the other hand, the presentation of gastric adenocarcinoma arising from a heterotopic pancreas is rare. This paper reports a case of gastric adenocarcinoma arising from a heterotopic pancreas that presented as a gastric outlet obstruction 10 years after the initial diagnosis of a suspicious submucosal tumor. Endoscopy revealed a pyloric stricture with prepyloric wall thickening and a complete gastric outlet obstruction. Abdominal and pelvic computed tomography exposed a severely distended gastric lumen at the antrum with heterogeneously enhancing circumferential wall thickening in the prepyloric antrum and pylorus. Because conservative treatment was ineffective and a malignancy could not be excluded, laparoscopic subtotal gastrectomy with a gastrojejunostomy was performed for histological confirmation and treatment. The histopathology diagnosis was advanced gastric carcinoma arising from heterotopic pancreatic tissue.

Comparison between cap-assisted and ligation-assisted endoscopic mucosal resection for rectal neuroendocrine tumors.

BACKGROUND: Modified endoscopic mucosal resection (EMR) is considered a treatment option for rectal neuroendocrine tumors (NETs) <10 mm in diameter. In this study, we evaluated the clinical outcomes of cap-assisted EMR (EMR-C) and EMR with a ligating device (EMR-L). METHODS: We retrospectively analyzed 158 patients with 162 rectal NETs treated endoscopically at a single Korean tertiary hospital between March 2010 and November 2017. We evaluated the rates of endoscopic en bloc resection, histologic complete resection, and procedural complications according to the treatment method. RESULTS: Among 162 rectal NETs, 42 were treated with EMR-C and 120 with EMR-L. The endoscopic en bloc resection rate was higher in the EMR-L group than in the EMR-C group (100% vs. 92.9%, P=0.003). A trend was observed towards a superior histologic complete resection rate in the EMR-L group, but it was not statistically significant (92.5% vs. 83.3%, P=0.087). There were no significant differences in procedural complications (P=0.870). In a multivariate analysis, a tumor located ≥10 cm from the anal verge was related to histologic incomplete resection (P=0.039). CONCLUSION: EMR-L may be the preferable treatment method, considering both endoscopic en bloc resection rate and histologic complete resection rate.

Predictive value for lymph node metastasis of epithelial-mesenchymal transition and cancer stem cell marker expression in early gastric cancer.

BACKGROUND: Minimally invasive therapies, including endoscopic mucosal resection or sentinel node navigation surgery, have been widely applied in early gastric cancer because of their benefits in promoting patient quality of life. However, lymph node dissection is beyond the capability of endoscopic therapy, and in sentinel node navigation surgery, the potential for skip metastasis is not negligible. Therefore, the possibility of lymph node metastasis is the most important factor to consider when deciding whether to apply the minimally invasive therapies. In the present study, the significance of epithelial mesenchymal transition and stem cell marker expression in lymph node metastasis in early gastric cancer was investigated. METHODS: We evaluated the significance of the expression of 5 epithelial mesenchymal transition-related markers (E-cadherin, MMP7, S100A, Snail-1, and HGF) and 6 stem cell markers (ALDH1, SOX2, CD24, CD44, CD54, and CD133) in 119 early gastric cancer specimens using immunohistochemistry. Because protein expression is heterogeneous in gastric cancer, we analyzed the expression of these markers in two selected regions (one each at the superficial zone and the deep invasive front). RESULTS: Expression of E-cadherin, MMP7, HGF, and CD133 at the deep invasive front was associated with the absence of lymph node metastasis (P=0.013, 0.018, <0.001, and 0.026, respectively). Presence of diffuse-type component, lymphatic invasion, and lack of expression of HGF and CD133 at the deep invasive front were independent predictive markers of lymph node metastasis (P=0.019, <0.001, 0.015, and 0.047, respectively). CONCLUSIONS: Lymph node metastasis is strongly associated with expression status of HGF and CD133 at the deep invasive front, suggesting the usefulness of these proteins as independent predictive markers of lymph node metastasis in early gastric cancer.