Immune signature as a potential marker for predicting response to immunotherapy in obesity-associated colorectal cancer.

BACKGROUND AND AIM: It remains unclear whether immunotherapy, which is not generally considered for microsatellite stable (MSS) colorectal cancer (CRC), can be used to effectively treat select CRC patients. We investigated the feasibility of obesity-associated MSS CRC patients for immunotherapy based on genomic alterations. METHODS: We evaluated differences in genomic alteration types and immune signatures between obese and non-obese patients with MSS CRC. We performed genomic analyses using 434 CRC patients from The Cancer Genome Atlas (TCGA). Patients with MSS CRC were stratified into subgroups based on their BMI and numbers of nonsynonymous single nucleotide variants (nsSNVs) and frameshift insertions and deletions (fs INDELs) using machine learning. RESULTS: The obese subgroup showed higher incidences of single nucleotide variants (SNV) and insertions and deletions (INDELs) in comparison with healthy weight patients with MSS CRC. The subgroup, who had higher numbers of nsSNVs and fs INDLEs, exhibited increased immune signatures, increased number of SNV-derived neoantigens, and had up-regulated two immune checkpoint genes in comparison with healthy weight patients with MSS CRC, reflecting interactions between the cancer genome and immune system. CONCLUSIONS: This study suggests that immunotherapy may be suitable for some obesity-associated CRC patients.

Nuclear features of papillary thyroid carcinoma: Comparison of Core needle biopsy and thyroidectomy specimens.

BACKGROUND: Core needle biopsy (CNB) has been used as an alternative or a complementary method for diagnosis of thyroid nodules. However, morphological analysis of the nuclear features of papillary thyroid carcinoma (PTC) cells obtained via CNB remains unclear. Hence, we examined the differences between the PTC nuclear features in CNB and thyroidectomy specimens. METHODS: Ten PTC patients, who underwent both CNB and thyroidectomy, were selected. Microscopic photographs of three representative areas of the PTC and adjacent parenchyma were taken. Ten cells per photograph were chosen, and 1200 cells were evaluated (300 PTC and 300 follicular cells in the CNB and thyroidectomy specimens, respectively). The area, circumference, major axis, and minor axis were measured using an image analyzer. Detailed nuclear features (size and shape, membrane irregularity, chromatin characteristics) were scored using a 3-point scale. RESULTS: The mean nuclear area, circumference, major axis, and minor axis of PTC cells in the CNB specimen were 1.76, 1.34, 1.34, and 1.29 times larger than those of the follicular cells (p<0.001); similar results were seen in the thyroidectomy specimens (2.04, 1.41, 1.37, and 1.37: p<0.001). Comparative analysis revealed that these parameters were significantly smaller in the CNB specimens than those in the thyroidectomy specimens (p<0.001). Nuclear grades were also lower in the former owing to poor chromatin characteristics (clearing and margination) (p<0.01). CONCLUSION: Considering that the PTC nuclei in CNB specimens are smaller with fewer irregularities and less clear than those in thyroidectomy specimens, we need to emphasize caution when using CNB specimens for diagnosis.

A robust model training strategy using hard negative mining in a weakly labeled dataset for lymphatic invasion in gastric cancer.

Gastric cancer is a significant public health concern, emphasizing the need for accurate evaluation of lymphatic invasion (LI) for determining prognosis and treatment options. However, this task is time-consuming, labor-intensive, and prone to intra- and interobserver variability. Furthermore, the scarcity of annotated data presents a challenge, particularly in the field of digital pathology. Therefore, there is a demand for an accurate and objective method to detect LI using a small dataset, benefiting pathologists. In this study, we trained convolutional neural networks to classify LI using a four-step training process: (1) weak model training, (2) identification of false positives, (3) hard negative mining in a weakly labeled dataset, and (4) strong model training. To overcome the lack of annotated datasets, we applied a hard negative mining approach in a weakly labeled dataset, which contained only final diagnostic information, resembling the typical data found in hospital databases, and improved classification performance. Ablation studies were performed to simulate the lack of datasets and severely unbalanced datasets, further confirming the effectiveness of our proposed approach. Notably, our results demonstrated that, despite the small number of annotated datasets, efficient training was achievable, with the potential to extend to other image classification approaches used in medicine.

Clinicopathologic Significance of Heat Shock Protein 60 as a Survival Predictor in Colorectal Cancer.

The role of heat shock protein 60 (HSP60), a mitochondrial chaperone, in tumor progression or its anti-tumor effects remains controversial. This study aimed to confirm the possibility of using HSP60 as a prognostic marker in patients with colorectal cancer (CRC), considering TNM classification for precise prediction. HSP60 expression increased with differentiation and p53 mutations in patients. However, compared to patients with high HSP60 expression, patients with low HSP60 expression had event-free survival and disease-specific survival hazard ratios (HRs) of 1.42 and 1.69, respectively. Moreover, when the survival rate was analyzed by combining TNM classification and HSP60 expression, the prognosis was poor, particularly when HSP60 expression was low in the late/advanced stage. This pattern was also observed with HSP family D member 1, HSPD1, the gene that encodes HSP60. Low HSPD1 expression was linked to lower overall survival and relapse-free survival rates, with HRs of 1.80 and 1.87, respectively. When TNM classification and HSPD1 expression were considered, CRC patients with low HSPD1 expression and advanced malignancy had a poorer prognosis than those with high HSPD1 expression. Thus, HSPD1/HSP60 can be a useful biomarker for a sophisticated survival prediction in late- and advanced-stage CRC, allowing the design of individualized treatment strategies.

Significance of 8-OHdG Expression as a Predictor of Survival in Colorectal Cancer.

The incidence of colorectal cancer (CRC) is increasing worldwide. 8-hydroxy-2'-deoxyguanosine (8-OHdG), one of the most prevalent DNA alterations, is known to be upregulated in several carcinomas; however, 8-OHdG has not been used to predict the prognosis of patients with CRC. We aimed to determine 8-OHdG levels in patients with CRC using immunohistochemistry and conducted a survival analysis according to the pathological stage. The 5-year event-free survival (EFS) and disease-specific survival (DSS) hazard ratios (HRs) of the low 8-OHdG subgroup were 1.41 (95% confidence interval (CI): 1.01-1.98, p = 0.04) and 1.60 (95% CI: 1.12-2.28, p = 0.01), respectively. When tumor node metastasis (TNM) staging and 8-OHdG expression were combined, the 5-year EFS and DSS HRs of patients with CRC with low 8-OHdG expression cancer at the same TNM stage (stage Ⅲ/Ⅳ) were 1.51 (95% CI: 1.02-2.22, p = 0.04) and 1.64 (95% CI: 1.09-2.48, p = 0.02), respectively, compared to those with high 8-OHdG expression cancer, indicating a poor prognosis. Therefore, low 8-OHdG expression is a significant predictive factor for 5-year EFS and DSS in patients with CRC, and it can serve as an essential biomarker of CRC.

Epithelial-mesenchymal transition in breast cancer correlates with high histological grade and triple-negative phenotype.

AIMS: Epithelial-mesenchymal transition (EMT) is characterized by a loss of epithelial nature and the acquisition of a mesenchymal form. The aim of this study was to assess the role of EMT in human mammary carcinogenesis, by performing immunohistochemical studies of EMT markers with tissue microarrays. METHODS AND RESULTS: A total of 492 cases were evaluated and classified as hormone receptor (HR)-positive type, HER2 type and triple-negative (TN) type by the use of immunohistochemistry and in-situ hybridization. We compared these groups in terms of epithelial and mesenchymal marker expression patterns. Of the 102 cases of TN-type breast cancer, 24.5% expressed vimentin, 13.7% expressed N-cadherin, and 9.8% expressed smooth muscle actin (SMA). Of the 221 cases of HR-type breast cancer, 4.1% expressed vimentin, 5.9% expressed N-cadherin, and 0.4% expressed SMA. Regarding epithelial markers, decreased expression was seen in 16.7% of cases for E-cadherin, in 45.1% for cytokeratin (CK)19 and in 60.8% for CK8 and CK18 (CAM5.2) in TN-type breast cancer cases. Decreased expression was seen in 11.8% of cases for E-cadherin, in 6.8% for CK19 and in 3.2% for CAM5.2 in HR-type cases. CONCLUSIONS: EMT features were particularly seen in TN-type breast cancer (P < 0.001). EMT was also significantly associated with high histological grade (P < 0.001).

Significance of Altered Fatty Acid Transporter Expressions in Uterine Cervical Cancer and Its Precursor Lesions.

BACKGROUND: High-risk human papilloma virus (HR HPV) infection is a major factor leading to the development of uterine cervical cancer. Data suggest that alterations in lipid metabolism are related to the pathogenesis of cervical cancer. Specifically, the uptake of exogenous fatty acids and their intracellular storage in lipid droplets enables cancer cells to survive and adapt to the changing tumor environment. MATERIALS AND METHODS: We compared the immunohistochemical expression of fatty acid transport protein 4 (FATP4), and cluster of differentiation 36/fatty acid translocase (CD36/FAT) in normal cervical epithelium, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and squamous cell carcinoma (SCC) tissues of the uterine cervix. We also investigated the clinicopathological implications of these fatty acid transporters in SCC. RESULTS: Compared with that in normal cervical tissues, the expression of FATP4 was lower in LSIL (p=0.002), HSIL (p=0.006), and SCC (p=0.001). In contrast, CD36 expression was higher in SCC tissues than in normal cervical tissues (p<0.001). In normal cervical tissues, HR HPV-infected lesions exhibited a decrease in FATP4 (p<0.001) and an increase of CD36 (p=0.134), compared to those that were not infected with HR HPV. High CD36 expression was associated with a shorter recurrence-free survival (p<0.001). However, high FATP4 levels showed no significant correlation with the clinicopathological parameters of SCC. CONCLUSION: Altered expression levels of FATP4 and CD36 are unique features that might be related to HR HPV infection and promote tumorigenesis and progression of cervical cancer.

Primary schwannoma of the thyroid gland: a case report.

BACKGROUND: Primary schwannomas of the thyroid gland are extremely rare. These tumors most often present as asymptomatic solitary neck masses, slow growing and rarely malignant. Only 15 cases of intrathyroidal schwannoma have been reported in the literature, and few have been reported with fine needle aspiration (FNA) cytology. CASE: A 14-year-old male patient presented with an asymptomatic left intrathyroidal mass. Radiologic studies revealed a circumscribed, marked hypoechoic mass with cystic portions in the left lobe of the thyroid gland on ultrasonography, pushing the trachea toward the right, visible side on computed tomography. FNA cytology of the mass exhibited a paucicellular smear composed of predominantly round to oval-shaped cells and occasional ovoid to spindle-shaped cells in loosely cohesive aggregates. On pathologic examination, the mass measured 60 x 45 x 30 mm and consisted of spindle-shaped cells arranged in fascicles in a whorling pattern in association with alternating hypercellular and hypocellular areas. CONCLUSION: Awareness of and understanding of the cytopathologic and radiologic characteristics of this entity are helpful in preoperative evaluation and correct treatment of intrathyroidal schwannoma.

HER2 as a potential biomarker of lymph node metastasis in undifferentiated early gastric cancer.

Human epidermal growth factor receptor 2 (HER2) is implicated in several cancers, including gastric cancer. However, limited data are available regarding its clinical significance in early gastric cancer (EGC). We evaluated the clinical significance of HER2 overexpression in patients with EGC. We retrospectively reviewed 727 patients who underwent surgical treatment for EGC between October 2010 and August 2017. HER2 expression was analysed in 680 EGC cases by immunohistochemistry and classified as negative (0 and 1+), equivocal (2+), or positive [overexpression (3+)]. Among patients with differentiated EGC, the number of patients with HER2 overexpression was not significantly different from that of HER2-negative patients in terms of age, sex, tumour size, location, gross type, depth of invasion, presence of lymphovascular invasion (LVI), and presence of lymph node metastasis (LNM). However, in patients with undifferentiated EGC, HER2 overexpression was significantly correlated with LVI and presence of LNM compared with HER2-negative patients. Multivariate analysis indicated HER2 overexpression as a good predictive marker of LNM in patients with undifferentiated EGC. HER2 expression is associated with LNM in undifferentiated EGC. Therefore, the importance of HER2 overexpression in EGC should not be overlooked, and further studies are needed to identify its clinical significance.

Comparison of papanicolaou smear and human papillomavirus (HPV) test as cervical screening tools: can we rely on HPV test alone as a screening method? An 11-year retrospective experience at a single institution.

BACKGROUND: The decrease in incidence of cervical dysplasia and carcinoma has not been as dramatic as expected with the development of improved research tools and test methods. The human papillomavirus (HPV) test alone has been suggested for screening in some countries. The National Cancer Screening Project in Korea has applied Papanicolaou smears (Pap smears) as the screening method for cervical dysplasia and carcinoma. We evaluated the value of Pap smear and HPV testing as diagnostic screening tools in a single institution. METHODS: Patients co-tested with HPV test and Pap smear simultaneously or within one month of each other were included in this study. Patients with only punch biopsy results were excluded because of sampling errors. A total of 999 cases were included, and the collected reports encompassed results of smear cytology, HPV subtypes, and histologic examinations. RESULTS: Sensitivity and specificity of detecting high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were higher for Pap smears than for HPV tests (sensitivity, 97.14%; specificity, 85.58% for Pap smears; sensitivity, 88.32%; specificity, 54.92% for HPV tests). HPV tests and Pap smears did not differ greatly in detection of low-grade squamous intraepithelial lesion (85.35% for HPV test, 80.31% for Pap smears). When atypical glandular cells were noted on Pap smears, the likelihood for histologic diagnosis of adenocarcinoma following Pap smear was higher than that of high-risk HPV test results (18.8 and 1.53, respectively). CONCLUSIONS: Pap smears were more useful than HPV tests in the diagnosis of HSIL, SCC, and glandular lesions.

Genetic alterations and chemosensitivity profile in newly established human renal collecting duct carcinoma cell lines.

OBJECTIVE: To determine the genetic alterations and chemosensitivity profile of collecting duct carcinoma (CDC) of the kidney, as it is a rare, highly aggressive malignant tumour with frequent distant metastases. MATERIALS AND METHODS: We first established and characterized two human CDC cell lines designated AP3 and AP8, respectively. The CDC cell lines were assessed using microarray-based comparative genomic hybridization and chemosensitivity testing. RESULTS: The CDC cells grew in vitro as an adherent monolayer with epithelial morphology, but had different growth rates. The cell lines had the characteristic immunophenotype of CDC (high molecular weight cytokeratin-+ve/cytokeratin 7-+ve/vimentin-+ve). Both cell lines shared copy number gains in chromosomes 20 and X. The loci showing a copy number gain were SOX22 at 20p tel, topoisomerse I (TOP1) at 20q12-q13.1, TPD52L2 at 20q tel, 20QTEL14 at 20q tel, KAL at Xp22.3, STS 5' at Xp22.3, OCRL1 at Xq25, AR3'at Xq11-q12, and XIST at Xq13.2, respectively. Immunoblot analysis confirmed that the AP3 and AP8 cell lines showed moderate and high levels of TOP1 expression, respectively. By chemosensitivity testing, the AP8 cells were most sensitive to topoisomerase I and II inhibitors such as topotecan, epirubicin and doxorubicin, but the AP3 cells did not. The chemosensitivity to these drugs was paralleled by cell death via apoptosis. CONCLUSION: The results suggest that TOP1 might be one of the molecular targets in AP8 CDC cells. Thus, these novel CDC cell lines will be useful for discovering therapeutic targets and developing effective anticancer drugs against CDC.

Clinicopathological and molecular characteristics of Epstein-Barr virus-associated gastric carcinoma: a meta-analysis.

There is conflicting data regarding the clinicopathological significance of the risk factors associated with Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC). To address this controversy, we performed a meta-analysis for the clinicopathological and molecular characteristics of EBVaGC. The relevant published studies were reviewed according to the defined selection criteria. The effect sizes of the outcome parameters were estimated by an odds ratio or a weighted mean difference. This meta-analysis included 48 studies that encompassed a total of 9738 patients. The frequency of EBVaGC was 8.8%, and EBVaGC was significantly associated with ethnicity. It was more predominant in men and in younger individuals. Interestingly, EBVaGC was more prevalent in Caucasian and Hispanic patients than in Asian ones. EBVaGC developed most often in the cardia and body, and it generally showed the diffuse histological type. EBV was highly prevalent in the patients with lymphoepithelial carcinoma. EBVaGC was closely associated with remnant cancer and a CpG island methylator-high status, but not with Helicobacter pylori infection, a TP53 expression, and p53 mutation. In addition, EBVaGC was not significantly associated with the depth of invasion, lymph node metastasis, or the clinical stage. The clinicopathological and molecular characteristics of EBVaGC are quite different from those of conventional gastric adenocarcinoma. However, further study is needed to determine the effect of EBV on the survival of EBVaGC patients.

Sex-specific differences in risk factors of lymph node metastasis in patients with early gastric cancer.

Accurate prediction of lymph node status is of crucial importance in the appropriate treatment planning for patients with early gastric cancer (EGC). Some studies have examined factors predicting lymph node metastasis (LNM) in EGC; however, these studies did not consider sex-specific differences. This study aimed to investigate sex-specific differences in predictive risk factors of LNM in EGC based on surgical specimens. Patients who underwent surgical treatment for EGC between January 2003 and February 2016 were retrospectively evaluated. Patients who underwent previous gastric surgery or treatment for gastric neoplasms were excluded. Finally, 1076 patients treated for EGC were included in the analysis. We analyzed risk factors of LNM by dividing patients into male and female groups. Of 1076 patients (mean age 59.6 years), 69% were men. The overall LNM rate was 9.4%. The LNM rate was lower in men (7.8%) than in women (12.9%). Multivariate analysis showed that elevated type (odds ratio [OR], 2.084; 95% confidence interval [CI]: 1.053-4.125; P = 0.035), submucosal invasion (OR, 2.162; 95% CI: 1.018-4.595; P = 0.045), undifferentiated type (OR, 2.044; 95% CI: 1.107-3.772; P = 0.022), and lymphovascular invasion (LVI) (OR, 7.210; 95% CI: 3.835-13.554; P<0.001) were independent predictive risk factors of LNM in EGC in men. However, only submucosal invasion (OR, 8.772; 95% CI: 2.823-27.259; P<0.001) and LVI (OR, 8.877; 95% CI: 3.861-20.410; P<0.001) were independent predictive risk factors of LNM in EGC in women. Submucosal invasion and LVI were risk factors of LNM in both men and women. However, elevated and undifferentiated types were risk factors in men but not in women. Clinicians should consider these sex-specific differences with regard to individualized management.

Intraoperative Frozen Cytology of Central Nervous System Neoplasms: An Ancillary Tool for Frozen Diagnosis.

BACKGROUND: Pathologic diagnosis of central nervous system (CNS) neoplasms is made by comparing light microscopic, immunohistochemical, and molecular cytogenetic findings with clinicoradiologic observations. Intraoperative frozen cytology smears can improve the diagnostic accuracy for CNS neoplasms. Here, we evaluate the diagnostic value of cytology in frozen diagnoses of CNS neoplasms. METHODS: Cases were selected from patients undergoing both frozen cytology and frozen sections. Diagnostic accuracy was evaluated. RESULTS: Four hundred and fifty-four cases were included in this retrospective single-center review study covering a span of 10 years. Five discrepant cases (1.1%) were found after excluding 53 deferred cases (31 cases of tentative diagnosis, 22 cases of inadequate frozen sampling). A total of 346 cases of complete concordance and 50 cases of partial concordance were classified as not discordant cases in the present study. Diagnostic accuracy of intraoperative frozen diagnosis was 87.2%, and the accuracy was 98.8% after excluding deferred cases. Discrepancies between frozen and permanent diagnoses (n = 5, 1.1%) were found in cases of nonrepresentative sampling (n = 2) and misinterpretation (n = 3). High concordance was observed more frequently in meningeal tumors (97/98, 99%), metastatic brain tumors (51/52, 98.1%), pituitary adenomas (86/89, 96.6%), schwannomas (45/47, 95.8%), high-grade astrocytic tumors (47/58, 81%), low grade astrocytic tumors (10/13, 76.9%), non-neoplastic lesions (23/36, 63.9%), in decreasing frequency. CONCLUSIONS: Using intraoperative cytology and frozen sections of CNS tumors is a highly accurate diagnostic ancillary method, providing subtyping of CNS neoplasms, especially in frequently encountered entities.

Analysis of satisfaction and academic achievement of medical students in a flipped class.

PURPOSE: The purpose of this study was to examine the satisfaction of medical students in flipped learning and analyzed academic achievement in comparison with lecture class. METHODS: The subjects were 40 students who participated in flipped learning during neurology course in the second year. After performing flipped learning, formative assessment was conducted and the degree of satisfaction was examined. Questionnaires of satisfaction were developed to identify the perceptions of students on flipped learning. To compare the academic achievement of students, formative assessments were conducted at the end of the flipped learning class and the lecture class. The data was analyzed by frequency and paired t-test method. RESULTS: The students showed a high level of frequency in using lecture notes (80.6%) and lecture slides (74.2%) among the pre-class learning resources. The average score (3.89) was higher for the factor of interaction and collaboration in the classroom than for the factor of improving learning (3.62). The average score of the students in the formative assessment was 4.28 points (out of 10 points) in the lecture class, while it was 5.56 points (out of 10 points) in the flipped learning class thus showing a statistically significant difference (t=-4.203, p<0.001). CONCLUSION: It was observed from the responses of the students that flipped learning is helpful for the interaction and collaboration in the classroom. It is expect that this result will be useful as basic data for medical school to try flipped learning in the future.

Improvement of diagnostic performance of pathologists by reducing the number of pathologists responsible for thyroid fine needle aspiration cytology: An institutional experience.

BACKGROUND: Various efforts have been made to improve the diagnostic accuracy of thyroid fine needle aspiration (FNA) cytology. We changed the diagnostic system by reducing the number of pathologists responsible for the thyroid FNA cytology in the routine work, and analyzed the effect on the pathologist's diagnostic performance. METHODS: Since March 1, 2015, 3 pathologists have been responsible for diagnostic thyroid FNA, previously undertaken by 9 equally. We compared the prechange period (three months, 319 nodules) and the postchange period (12 months, 1194 nodules). RESULTS: The turnaround time was shortened from 1.4 ± 0.7 days to 0.9 ± 0.5 days (P < .001). The utilization rate of the Bethesda system for Reporting Thyroid Cytopathology (TBSRTC) increased from 92.5% to 99.8%. Diagnostic rates of categories that are confirmative [II (benign) and VI (malignant)] increased, while the inadequate (I) or indeterminate (III) categories decreased. With category IV (follicular neoplasm), a challenging category in our country, an elevated malignancy rate was found at follow-up. Overall, the diagnostic performance was improved in terms of sensitivity (from 98.5% to 99.2%) and specificity (from 94.4% to 98.4%), with reduced false-negative rates (from 1.5% to 0.8%) and false-positive rates (from 2.9% to 1.1%). The area under the receiver operating characteristic curve increased from 0.861 to 0.958. CONCLUSION: Reducing the number of pathologists responsible for diagnostic thyroid FNA cytology resulted in a higher utilization rate of TBSRTC, and more rapid and accurate diagnosis.

Comparison of sporadic sclerotic fibroma and solitary fibrous tumor in the oral cavity.

Sporadic sclerotic fibroma (SF) and solitary fibrous tumor (SFT) arising in the oral cavity are very rare. In this report, we describe two cases of oral pathology, one involving SF and the other involving SFT. Both cases presented with well- circumscribed, firm nodules with similar gross findings. However, the histologic findings of the SF and SFT showed rather distinct features. The SF was composed of hyalinized sclerotic collagen bundles arranged in a whorled pattern, whereas the SFT was formed by spindles cells arranged in hypo- and hypercellular areas. The immunohistochemical findings were similar in both cases; there was positivity for vimentin, CD34, and CD99, but bcl-2 positivity was only seen in the SFT. Although their histopathologies are similar, SF and SFT should be considered in the differential diagnosis of soft tissue tumors in the oral cavity.

Granular cell tumors of the abdominal wall.

Granular cell tumors (GCT) are found in virtually any body site, including the tongue, skin, subcutaneous tissue, breast, rectum and vulva. However, they are rarely seen in the abdominal wall. We report here on a rare case of GCT in the rectus muscle of the abdominal wall. A 44-year-old woman presented with a non-tender, hard mass in the right lower abdominal wall. Upon microscopic examination, the tumor was found to comprise of large polygonal cells with an abundant eosinophilic granular cytoplasm and round to oval nuclei. Upon immunohistochemical staining, the large cells showed S-100 and CD68 positive granular aggregates in the cytoplasm. Many lysosomes of variable size were observed in the cytoplasm.

Predictive risk factors associated with synchronous multiple early gastric cancer.

The aim of this study was to elucidate the predictive risk factors of synchronous multiple early gastric cancer regardless of the treatment modality.Patients who underwent early gastric cancer treatment between July 2005 and June 2015 were retrospectively reviewed. In total, 1529 patients who were treated for early gastric cancer were included. We analyzed the patient's data to find predictive factors of synchronous multiple early gastric cancer compared to solitary early gastric cancer. Further analysis was performed to verify the difference between endoscopic and surgical treatment groups.Among the 1529 patients, synchronous multiple early gastric cancer was diagnosed in 68 (4.4%) patients. Significant differences in sex (P = .004), gross appearance (P = .038), depth of invasion (P = .007), and lymphovascular invasion (P = .039) were found between patients with solitary early gastric cancer and synchronous multiple early gastric cancer by univariate analysis. In multivariate analysis, male sex (odds ratio, 2.475; P = .011) and submucosal invasion (odds ratio, 1.850; P = .033) were independent predictive risk factors of synchronous multiple early gastric cancer. In addition, in multivariate analysis, significant differences in age, tumor size, longitudinal location, depth of invasion, and histology were found between patients groups depending on the mode of treatment.Male sex and submucosal invasion were predictive risk factors of synchronous multiple early gastric cancer. Patients with these factors should undergo more meticulous endoscopic surveillance.

Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer.

Gastric cancer (GC), one of the most common cancers worldwide, has a high mortality rate due to limited treatment options. Identifying novel and promising molecular targets is a major challenge that must be overcome if treatment of advanced GC is to be successful. Here, we used comparative genomic hybridization and gene expression microarrays to examine genome-wide DNA copy number alterations (CNAs) and global gene expression in 38 GC samples from old and young patients. We identified frequent CNAs, which included copy number gains on chromosomes 3q, 7p, 8q, 20p, and 20q and copy number losses on chromosomes 19p and 21p. The most frequently gained region was 7p21.1 (55%), whereas the most frequently deleted region was 21p11.1 (50%). Recurrent highly amplified regions 17q12 and 7q31.1-7q31.31 harbored two well-known oncogenes: ERBB2 and MET. Correlation analysis of CNAs and gene expression levels identified CAPZA2 (co-amplified with MET) and genes GRB7, MIEN1, PGAP3, and STARD3 (co-amplified with ERBB2) as potential candidate cancer-promoting genes (CPGs). Public dataset analysis confirmed co-amplification of these genes with MET or ERBB2 in GC tissue samples, and revealed that high expression (except for PGAP3) was significantly associated with shorter overall survival. Knockdown of these genes using small interfering RNA led to significant suppression of GC cell proliferation and migration. Reduced GC cell proliferation mediated by CAPZA2 knockdown was attributable to attenuated cell cycle progression and increased apoptosis. This study identified novel candidate CPGs co-amplified with MET or ERBB2, and suggests that they play a functional role in GC.