Jung Yeon Kim

Adenocarcinoma of the small intestine: a multi-institutional study of 197 surgically resected cases

Small intestinal adenocarcinoma is a rare malignant neoplasm, and its clinicopathologic characteristics have not been well elucidated. A total of 197 small intestinal adenocarcinoma cases were collected from 22 institutions in South Korea and were evaluated for clinicopathologic factors that affect the prognosis of small intestinal adenocarcinoma patients using univariate and multivariate analyses. The mean patient age was 59 years, and the male-to-female ratio was 1.7:1. Tumors were located in the duodenum of 108 cases (55%), the jejunum in 59 (30%), and the ileum in 30 (15%). Predisposing conditions were observed in 23 cases (12%), including 17 cases with sporadic adenomas, 3 with Peutz-Jeghers syndrome, 2 with Meckel diverticulum, and 1 with Crohn disease. Synchronous or metachronous malignant tumors were identified in 31 cases (16%), including 13 colorectal and 10 stomach cancers. About 90% of tumors were classified as either pT3 (63 cases) or pT4 (112 cases). The median survival time for all small intestinal adenocarcinoma patients was 39.7 months. Compared with small intestinal adenocarcinomas without accompanying sporadic adenomas, small intestinal adenocarcinomas with accompanying adenomas were more well differentiated (P < .0001), with a more polypoid growth pattern (P < .0001), a lower pT classification (P < .0001), less perineural invasion (P = .01), and less lymphatic invasion (P = .03). Small intestinal adenocarcinoma patients with associated sporadic adenomas (77%) had a significantly better 5-year survival rate than those without sporadic adenomas (38%, P = .02). By univariate analysis, small intestinal adenocarcinoma patients had significantly different survival based on pT classification (P = .003), lymph node metastasis (P < .0001), distal location (jejunal and ileal carcinomas) (P = .003), retroperitoneal tumor seeding (P < .0001), vascular invasion (P = .007), lymphatic invasion (P = .001), peritumoral dysplasia (P = .004), and radiation therapy (P = .006). By multivariate analysis, lymph node metastasis (P = .01) and distal location (P = .003) were independent predictors of a worse prognosis. In conclusion, (1) small intestinal adenocarcinomas are diagnosed at an advanced disease stage; therefore, the development of strategies for detection at an earlier stage is needed. (2) Small intestinal adenocarcinoma patients with an adenomatous component had a better survival than those without an adenomatous component. (3) Lymph node metastasis and distal location (jejunum and ileum) of tumor are the most important independent prognostic factors.

Expression of HuR is associated with increased cyclooxygenase-2 expression in uterine cervical carcinoma.

Summary: The human family embryonic-lethal abnormal vision-like protein Hu antigen R (HuR) serves as a messenger RNA (mRNA)-binding protein and stabilizes a certain group of cellular mRNAs that contain adenylate/uridylate-rich elements in their 3-untranslated region. The HuR is predominantly located in the nucleus, but it shuttles between the nucleus and the cytoplasm. In the cytoplasm, it can stabilize certain transcripts. Reportedly, the mRNA of cyclooxygenase-2 (COX-2) can be stabilized by HuR in breast, ovary, colon, stomach, lung, and brain cancers. We investigated the expression of HuR and COX-2 in 308 primary uterine cervical carcinomas using immunohistochemistry. Nuclear HuR expression was seen in 280 (90.9%) of the cases, and cytoplasmic HuR expression was observed in 61 (19.8%) of the cases. The expression of nuclear HuR was significantly associated with stage (P = 0.031). We found that 135 patients (43.8%) showed positive reaction for the COX-2 protein. In the COX-2 positive cases, nuclear HuR expression was higher, but the difference was not statistically significant. Cytoplasmic HuR expression was significantly associated with tumor size (P = 0.029), stage (P = 0.005), and lymphatic/vascular invasion (P < 0.001). Considering only squamous cell lesions (carcinoma in situ, microinvasive squamous cell carcinoma [SCC], and invasive SCC), the cytoplasmic expression of HuR significantly increased in invasive SCC compared with microinvasive SCC or carcinoma in situ (P = 0.005). Cytoplasm HuR expression correlated with COX-2 (P < 0.001). There was no significant correlation between HuR (nuclear or cytoplasmic) expression and patient survival. Our results suggest that the cytoplasmic overexpression of HuR is associated with uterine cervical carcinomas with aggressive clinicopathologic features and that HuR might contribute to the stabilization of COX-2 mRNA in some uterine cervical carcinomas.

Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes

This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve β-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients.

Cyclooxygenase-2 and c-erbB-2 expression in colorectal carcinoma assessed using tissue microarrays.

The c-erbB-2 and cyclooxygenase (COX) pathways are involved in the pathogenesis of colorectal carcinoma, but the relationship is not fully understood. This study evaluated the significance of c-erbB-2, COX-2, and Ki-67 protein expression in 185 patients with colorectal carcinoma using tissue microarrays. Only one case expressed c-erbB-2 protein. COX-2 expression was noted in 166 of 176 cases (94.3%), and the Ki-67 expression rate averaged 5.9%. There was no relationship among c-erbB-2, COX-2, and Ki-67 protein expression, and COX-2 protein expression was not related to tumor stage, differentiation, size, depth of invasion, lymphatic or vascular invasion, or patient survival. While the contribution of c-erbB-2 to colorectal carcinogenesis may be of little quantity, COX-2 may be deeply involved in colorectal carcinogenesis.

Mullerianosis of the mesosalpinx: a case report.

We report a case of mullerianosis of the mesosalpinx, the appearance of which simulated metastatic adenocarcinoma. The patient was a 37-year-old woman with a mixed epithelial cystadenoma of borderline malignancy associated with endometriosis in both ovaries. The left mesosalpinx contained a firm, 2.2-cm, gray-white mass that on microscopic examination consisted of glands lined mostly by endocervical-type epithelium with admixed tubal-type glands and foci of endometriosis. Rupture of glands with extravasation of mucin into the surrounding stroma was observed, but there was no desmoplastic stromal reaction. Awareness of this relatively uncommon lesion is critical to avoid misdiagnosis and overly aggressive treatment.

Osteopontin, CD44, and NFκB Expression in Gastric Adenocarcinoma

PURPOSEnOsteopontin (OPN) binds to CD44 and nuclear factor-kappaB (NFkappaB) and OPN mediates tumorigenesis, invasion and metastasis, but the interrelationships between OPN, CD44 and NFkappaB are not fully understood, and especially in gastric carcinogenesis. We examined the expressions of OPN, CD44, and NFkappaB in untreated gastric adenocarcinomas.nnnMATERIALS AND METHODSnThe materials from 211 cases of gastric adenocarcinoma were immunostained for OPN, CD44 and NFkappaB by using a tissue microarray. The OPN mRNA expression was measured in 10 cases by performing real-time RT-PCR.nnnRESULTSnThe expression of OPN, CD44 and NFkappaB was noted in 61.7%, 11.4% and 26.6% of the adenocarcinoma tissues, respectively. No significant correlation was detected among the expressions of these proteins. The OPN protein expression was negatively correlated with angioinvasion (p<0.05) and patient survival (p<0.05), whereas the CD44 and NFkappaB protein expressions were not correlated with any of the clinicopathological factors we examined. The depth of invasion, lymph node status and perineural invasions were prognostic factors based on the Cox analysis. The OPN mRNA expression showed no significant difference between the adenocarcinoma and the paired normal mucosa on real-time RT-PCR.nnnCONCLUSIONnOPN may have a currently undetermined role in gastric carcinogenesis, and CD44 and NFkappaB may have minor roles in gastric adenocarcinoma.

Genomic Aberrations in Salivary Duct Carcinoma Arising in Warthin Tumor of Parotid Gland: DNA Microarray and HER2 Fluorescence In Situ Hybridization

Carcinoma arising from Warthin tumor is extremely rare. A 79-year-old man was admitted for a firm, well-defined, 5-cm left infra-auricular mass. Aspiration cytology showed many lymphohistiocytes and oncocytes in a proteinaceous background, compatible with Warthin tumor. A left superficial parotidectomy showed a solid mass around the cyst wall. The tumor cells of the solid area were arranged as infiltrative ducts with a few foci of malignant transformation. Virtual karyotyping disclosed a complex pattern of genetic aberrations with a focal amplification in 12q14-q21.2. This chromosomal region contains the MDM2 (murine double minute) gene, which regulates p53 inactivation. HER2 fluorescence in situ hybridization showed a focal amplification. Subsequently, the patient underwent total parotidectomy and ipsilateral neck dissection for a recurrence. To our knowledge, this is the first case of salivary duct carcinoma arising from Warthin tumor. The essential molecular pathway has not been reported, we presume an important role of MDM2 amplification- P53 inactivation.

Fascin expression predicts lymph node metastasis and worse survival in small intestinal carcinoma

Summary Fascin expression has been associated with clinicopathological parameters and clinical outcome in many carcinomas. The aim of this study was to evaluate the prognostic impact of fascin expression in small intestinal carcinomas (SICs). We constructed tissue microarrays for evaluation of immunohistochemical expression of fascin in a total of 194 SICs. Fascin was expressed in 47 (24.2%) of the 194 SICs, and fascin expression showed an association with poorly and undifferentiated histology (pu200a<u200a0.001) and lymphatic invasion (pu200a=u200a0.019). No fascin expression was observed in tumour cells of metastatic lymph nodes in cases of SIC without fascin expression (pu200a<u200a0.001). Patients with fascin expression showed significantly shorter overall survival compared to patients without expression (pu200a=u200a0.001). In multivariate analysis, fascin expression was an independent prognostic factor in SIC patients (pu200a=u200a0.043). Fascin expression showed significant correlation with lack of differentiation and lymphatic invasion, and may be a useful predictive marker for lymph node metastasis. Fascin expression in SICs showed an association with poor overall survival and was an independent poor prognostic factor.

Molecular Testing for Gastrointestinal Cancer

With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

Prognostic Significance of a Micropapillary Pattern in Pure Mucinous Carcinoma of the Breast: Comparative Analysis with Micropapillary Carcinoma

Background Mucinous carcinoma of the breast is an indolent tumors with a favorable prognosis; however, micropapillary features tend to lead to aggressive behavior. Thus, mucinous carcinoma and micropapillary carcinoma exhibit contrasting biologic behaviors. Here, we review invasive mucinous carcinoma with a focus on micropapillary features and correlations with clinicopathological factors. Methods A total of 64 patients with invasive breast cancer with mucinous or micropapillary features were enrolled in the study. Of 36 pure mucinous carcinomas, 17 (47.2%) had micropapillary features and were termed mucinous carcinoma with micropapillary features (MUMPC), and 19 (52.8%) had no micropapillary features and were termed mucinous carcinoma without micropapillary features. MUMPC were compared with 15 invasive micropapillary carcinomas (IMPC) and 13 invasive ductal and micropapillary carcinomas (IDMPC). Results The clinicopathological factors of pure mucinous carcinoma and MUMPC were not significantly different. In contrast to IMPC and IDMPC, MUMPC had a low nuclear grade, lower mitotic rate, higher expression of hormone receptors, negative human epidermal growth factor receptor 2 (HER2) status, lower Ki-67 proliferating index, and less frequent lymph node metastasis (p < .05). According to univariate analyses, progesterone receptor, HER2, T-stage, and lymph node metastasis were significant risk factors for overall survival; however, only T-stage remained significant in a multivariate analysis (p < .05). Conclusions In contrast to IMPC and IDMPC, the micropapillary pattern in mucinous carcinoma does not contribute to aggressive behavior. However, further analysis of a larger series of patients is required to clarify the prognostic significance of micropapillary patterns in mucinous carcinoma of the breast.