HER2-positive mucinous cystadenocarcinoma of the breast coexisting with invasive lobular carcinoma: A case report and review of the literature.

Primary mucinous cystadenocarcinoma (MCA) of the breast is a rare variant of breast carcinoma. A 68-year-old female patient presented to the general surgery clinic with pain and swelling in the right breast. A mass was detected in the upper outer quadrant, and a fine-needle aspiration biopsy was performed. The May-Grünwald Giemsa stained slides showed aggregates of mucin-rich pleomorphic cells with large nuclei in a mucinous background containing discohesive single cells. The Papanicolaou stain revealed a papillary structure composed of malignant epithelial cells in a necrotic background. A modified radical mastectomy was performed, and upon gross examination, two tumors were discovered in the central and upper outer quadrants. The first tumor, located centrally, was identified as invasive lobular breast carcinoma. The second tumor was an MCA with cytokeratin 7(+) and cytokeratin 20(-), and was determined to be the primary MCA of the breast based on clinical and radiological information. Immunohistochemistry revealed that the tumor cells were negative for estrogen receptor and progesterone receptor, and HER2 was 2+. Fluorescence in situ hybridization analysis detected HER2 gene amplification. During the 72-month follow-up, there were no findings compatible with recurrence or new metastasis. Although primary MCA is rare, it causes differential diagnosis problems and has different biological behaviors.

Mucinous cystadenocarcinoma of the breast: a new entity with broad differentials-a case report.

BACKGROUND: Mucinous cystadenocarcinoma is a rare and recently described primary breast cancer with strikingly similar histomorphology to ovarian, pancreatic, and gastrointestinal counterparts. The diagnosis cannot be made until the metastatic lesion is ruled out. CASE PRESENTATION: We are reporting the case of a 65-year-old woman with primary mucinous cystadenocarcinoma of the breast while exploring clinicopathological features and approach to diagnosis. Though the immunohistochemistry panel of CK7, CK20, CDX2, SATB2, PAX8, mammoglobin, and GATA3 plays a crucial role in ruling out metastasis but aberrant CK20 positivity was seen in our case, the final diagnosis was made after a complete radiological workup. We also noted strong membranous HER2-protein expression and HER2-gene amplification by fluorescence in situ hybridization while in literature this tumor is reported to show mainly triple-negative basal type immunophenotype. CONCLUSION: A combined clinic-radio-immunohistochemical approach is essential to make a diagnosis of primary mucinous cystadenocarcinoma.

Different Prognostic Implications of Aquaporin-1 and Aquaporin-5 Expression among Different Histological Types of Ovarian Carcinoma.

The aquaporins (AQPs) are a family of transmembrane water channel proteins that are distributed in various human tissues. Recent studies have suggested that AQP expression correlates with various aspects of cancer biology that determine the aggressiveness of different cancers. Ovarian carcinoma is one of the most lethal gynecological cancers. Some studies have suggested that AQPs are expressed in ovarian carcinoma, and are associated with cancer cell growth and migration. In this study, we immunohistochemically evaluated the expression of AQP1, 3, 5, and 9 in a total of 300 ovarian carcinomas using tissue microarrays. In our analyses of correlations between aquaporin expression and overall survival, high AQP5 expression was significantly associated with poorer prognosis (P = 0.029). For AQP1, the low expression group trended towards poorer prognosis than the high expression group, but the difference was not statistically significant. When ovarian carcinomas were divided by histological types, high AQP5 expression correlated with poorer prognosis in serous carcinoma (P = 0.015), and low AQP1 expression correlated with poorer prognosis in clear cell carcinomas (P = 0.0055). By contrast, high AQP1 expression correlated with poorer prognosis in mucinous carcinoma (P = 0.0001) and endometrioid carcinoma (P = 0.021). Our studies suggest that AQPs can be useful prognostic markers in ovarian carcinoma, but their correlation with prognosis depends on the histological type of ovarian carcinoma.

Excellent Accuracy of Glucose Level in Cystic Fluid for Diagnosis of Pancreatic Mucinous Cysts.

BACKGROUND: CEA in pancreatic cystic fluid (PCF) is standard for mucinous cysts diagnosis. Glucose is an alternative, but its accuracy remains poorly described. AIMS: To evaluate PCF glucose using a glucometer and compare its accuracy with CEA for mucinous cysts diagnosis. MATERIALS AND METHODS: In frozen PCF obtained by EUS-FNA, glucose was evaluated using a glucometer. CEA and cytology were available as standard of care. The accuracy of glucose and CEA was calculated using receiver operator (ROC) curves. Definitive diagnoses were surgical or clinicopathological. RESULTS: We evaluated 82 patients with a mean age of 61.3 ± 14.8 years (25-91), predominantly (59%) females. Diagnoses included 17 serous cystadenomas, five pseudocysts, 20 intraductal papillary mucinous neoplasms, three mucinous cystic neoplasms, five adenocarcinomas, four neuroendocrine tumors, two other types, 26 non-defined. The median glucose levels (interquartile range) were 19 mg/dL (19-19) in mucinous and 105 mg/dL (96-127) in non-mucinous cysts (p < 0.0001). The median CEA level was 741 ng/mL (165-28,567) in mucinous and 9 ng/mL (5-19) in non-mucinous cysts (p < 0.0001). For mucinous cyst diagnosis, a CEA > 192 ng/mL had a sensitivity of 72% (95% CI 51-88) and a specificity of 96% (95% CI 82-100), and ROC analysis showed an area under the curve (AUC) of 0.842 (95% CI 0.726-0.959), while glucose < 50 mg/dL had a sensitivity of 89% (95% CI 72-98), a specificity of 86% (95% CI 67-96), and an AUC of 0.86 (95% CI 0.748-0.973). Pseudocysts presented low glucose, identically to mucinous cysts, with CEA allowing differential diagnosis. CONCLUSION: Glucose measured by a glucometer is accurate for mucinous cyst diagnosis, with significantly higher levels in non-mucinous cysts, except pseudocysts.

Urachal Mucinous Cystadenocarcinoma.

A 57-year-old man presented with a 6-month history of pelvic fullness. He had no lower urinary tract symptoms or altered bowel habits. On examination, there was a non-tender pelvic mass which extended from the pubic symphysis to the level of the umbilicus. CT scan of the abdomen demonstrated a 22×11×11 cm cystic mass arising from the pelvis extending into the midline and superiorly to the umbilicus. Other than raised carcinoembryonic antigen of 7.6 ng/mL (<5.0), the remainder of his blood test were unremarkable. Flexible cystoscopy demonstrated a convex deformity of the bladder wall in keeping with the compression and displacement as seen on the CT. The patient underwent an open excision of the cystic structure (urachal remnant), partial cystectomy, partial excision of anterior abdominal wall and pelvic lymphadenectomy. A check cystogram performed 12 days following the initial operation was unremarkable.

TFF3 Expression as Stratification Marker in Borderline Epithelial Tumors of the Ovary.

Borderline tumors (BOT) of the ovary account for 10% to 20% of ovarian neoplasms. Like ovarian cancer, BOT encompass several different histological subtypes (serous, mucinous, endometrioid, clear cell, transitional cell and mixed) with serous (SBOT) and mucinous (MBOT) the most common. Current hypotheses suggest low-grade serous carcinoma may develop in a stepwise fashion from SBOT whereas the majority of high grade serous carcinomas develop rapidly presumably from inclusion cysts or ovarian surface epithelium. The pathogenesis of mucinous ovarian tumors is still puzzling. Molecular markers could help to better define relationships between such entities. Trefoil factor-3 (TFF3) is an estrogen-regulated gene associated with prognosis in different types of cancer. It has also been included in a recent marker panel predicting subtypes of ovarian carcinoma. We analyzed the expression of TFF3 by immunohistochemistry in a cohort of 137 BOT and its association with histopathological features. Overall expression rate of TFF3 was 21.9%. None of the BOT with serous and endometrioid histology displayed strong TFF3 expression. On the other hand, TFF3 was highly expressed in 61.4% of MBOT cases and 33.3% of BOT with mixed histology (P < 0.001) suggesting a potential function of the protein in that subtypes. Associations of TFF3 expression with FIGO stage and micropapillary pattern were significant in the overall cohort but confounded by their correlation with histological subtypes. The highly specific expression of TFF3 in MBOT may help to further clarify potential relationships of tumors with mucinous histology and warrants further studies.

Positive expression of insulin-like growth factor-1 receptor is associated with a positive hormone receptor status in ovarian cancer.

UNLABELLED: Summary PURPOSE: Ovarian cancer is the most deadly of all gynecologic malignancies, due in part to the diagnosis at an advanced stage caused by the deficiency of specific marks and symptoms, by the absence of reliable tests for screening, and by early detection. MATERIALS AND METHODS: Insulin-like growth factor-I (IGF-I) is known to be involved in the development and promotion of diverse examples of solid tumors including ovarian cancer. IGF-I levels in local tissue are subject to both endocrine and paracrine/autocrine regulation. RESULTS: Most patients will react initially to treatment, but almost 70% of them will have a recurrence. Consequently, new therapeutic modalities are urgently required to overcome chemoresistance observed in ovarian cancer patients. IGF-1R expression was evaluated immunohistochemically in tissue microarray blocks constructed from 1,200 ovarian cancer samples collected from three medical institutions. CONCLUSION: Evidence accumulates suggesting that the insulin/insulin growth factor (IGF) pathways could play a good therapeutic target in various cancers, including ovarian cancer.

Trefoil factor 1 elevates the malignant phenotype of mucinous ovarian cancer cell through Wnt/ß-catenin signaling.

Mucinous ovarian cancer accounts for almost 10% of epithelial ovarian cancer, though patients in the early stage have an excellent prognosis, patients with advanced disease have a poor outcome and the molecular mechanism remains unclear. In this study, we retrieved database and found a secretory protein TFF1, which plays a tumor suppressor role in gastric cancer, is highly expressed in mucinous ovarian cancer, not serous or any other kind of ovarian cancer. Furthermore, the highly expressed TFF1 indicates a poor clinical outcome. Further biological function analysis revealed that TFF1 not only promotes cell proliferation but also invasion and chemoresistance, and these oncogenic effects might through regulating the activity of Wnt/ß-catenin signaling and the level of Twist. Taken together, we found TFF1 plays an oncogenic role in mucinous ovarian cancer, unlike its suppressive role in gastric cancer.

Primary mucinous cystadenocarcinoma of the testis: An extremely rare ovarian-type surface epithelial carcinoma.

Primary mucinous epithelial tumors of the testis are extremely rare. Although isolated case reports and small series have been published, these interesting neoplasms are less well-known. We report a case of a primary intratesticular mucinous cystadenoma in an asymptomatic 44-year-old man. Right radical orchiectomy was performed because a malignant testicular tumor was suspected. We discuss the management of this uncommon testicular tumor based on the limited reports.

Suboptimal accuracy of carcinoembryonic antigen in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large multicenter study.

BACKGROUND AND AIMS: The exact cutoff value at which pancreatic cyst fluid carcinoembryonic antigen (CEA) level distinguishes pancreatic mucinous cystic neoplasms (MCNs) from pancreatic nonmucinous cystic neoplasms (NMCNs) is unclear. The aim of this multicenter retrospective study was to evaluate the diagnostic accuracy of cyst fluid CEA levels in differentiating between MCNs and NMCNs. METHODS: Consecutive patients who underwent EUS with FNA at 3 tertiary care centers were identified. Patients with histologic confirmation of cyst type based on surgical specimens served as the criterion standard for this analysis. Demographic characteristics, EUS morphology, FNA fluid, and cytology results were recorded. Multivariate logistic regression analysis to identify predictors of MCNs was performed. Receiver-operating characteristic (ROC) curves were generated for CEA levels. RESULTS: A total of 226 patients underwent surgery (mean age, 61 years, 96% white patients, 39% female patients) of whom 88% underwent Whipple's procedure or distal pancreatectomy. Based on surgical histopathology, there were 150 MCNs and 76 NMCNs cases. The median CEA level was 165 ng/mL. The area under the ROC curve for CEA levels in differentiating between MCNs and NMCNs was 0.77 (95% confidence interval, 0.71-0.84, P < .01) with a cutoff of 105 ng/mL, demonstrating a sensitivity and specificity of 70% and 63%, respectively. The cutoff value of 192 ng/mL yielded a sensitivity of 61% and a specificity of 77% and would misdiagnose 39% of MCN cases. CONCLUSIONS: Cyst fluid CEA levels have a clinically suboptimal accuracy level in differentiating MCNs from NMCNs. Future studies should focus on novel cyst fluid markers to improve risk stratification of pancreatic cystic neoplasms.

Cyst Fluid Glucose is Rapidly Feasible and Accurate in Diagnosing Mucinous Pancreatic Cysts.

OBJECTIVES: Better diagnostic tools are needed to differentiate pancreatic cyst subtypes. A previous metabolomic study showed cyst fluid glucose as a potential marker to differentiate mucinous from non-mucinous pancreatic cysts. This study seeks to validate these earlier findings using a standard laboratory glucose assay, a glucometer, and a glucose reagent strip. METHODS: Using an IRB-approved prospectively collected bio-repository, 65 pancreatic cyst fluid samples (42 mucinous and 23 non-mucinous) with histological correlation were analyzed. RESULTS: Median laboratory glucose, glucometer glucose, and percent reagent strip positive were lower in mucinous vs. non-mucinous cysts (P<0.0001 for all comparisons). Laboratory glucose<50 mg/dl had a sensitivity of 95% and a specificity of 57% (LR+ 2.19, LR- 0.08). Glucometer glucose<50 mg/dl had a sensitivity of 88% and a specificity of 78% (LR+ 4.05, LR- 0.15). Reagent strip glucose had a sensitivity of 81% and a specificity of 74% (LR+ 3.10, LR- 0.26). CEA had a sensitivity of 77% and a specificity of 83% (LR+ 4.67, LR- 0.27). The combination of having either a glucometer glucose<50 mg/dl or a CEA level>192 had a sensitivity of 100% but a low specificity of 33% (LR+ 1.50, LR- 0.00). CONCLUSIONS: Glucose, whether measured by a laboratory assay, a glucometer, or a reagent strip, is significantly lower in mucinous cysts compared with non-mucinous pancreatic cysts.

Aberrant expression of pim-3 promotes proliferation and migration of ovarian cancer cells.

Pim kinase-3(Pim-3), a member of serine/threonine protein kinases, has been implicated in multiple human cancers and involved in Myc-induced tumorigenesis. However, little is known regarding its expression and biological function in human ovarian cancer. In this study we showed that the clinical significance and biological functions of Pim-3 in ovarian cancer and found that higher Pim-3 mRNA level are detected in ovarian cancer tissues than those in normal ovarian tissues. There are significant correlations between higher Pim-3 expression levels with the FIGO stage, histopathological subtypes, and distant metastasis in ovarian cancer patients. Lentivirus-mediated gene overexpression of Pim-3 significantly promotes the proliferation and migration of SKOV3 cell lines. Furthermore, MACC1 and Pim-3 expression were significantly correlated in human ovarian cancer cells, and overexpression of Pim-3 in ovary cancer cells increased MACC1 mRNA and protein expression. The data indicate that Pim-3 acts as a putative oncogene in ovary cancer and could be a viable diagnostic and therapeutic target for ovarian cancer.

Expression of sulfatide and sulfated lactosylceramide among histological types of human ovarian carcinomas.

Among negatively charged lipids, sulfoglycolipids are known to be expressed by specific cell populations and to be involved in their functions, including in adhesion with functional proteins, modification of ion channels and induction of cellular differentiation. Accordingly, we determined their amounts in several histologically defined types of ovarian carcinoma tissues. Sulfoglycolipids were determined by TLC-immunostaining with monoclonal anti-sulfatide antibodies and the gene expression of their synthetic enzymes was by RT-PCR. All types of ovarian carcinomas were revealed to exhibit potential to synthesize sulfoglycolipids, either sulfatide (I(3)SO3-GalCer) or sulfated lactosylceramides (II(3)SO3-LacCer), which were expressed at the following frequencies, 6 out of 6 mucinous cystadenocarcinomas, 4 out of 7 serous cystadenocarcinomas, 2 out of 3 endometrioid carcinomas, and 2 out of 3 clear cell adenocarcinomas. All mucinous cystadenocarcinoma tissues preferentially contained sulfatide in amounts of 0.61-1.13 µg per mg dry weight, the molecular species being similar with those of GalCer. Whereas the other carcinomas contained either sulfatide or sulfated LacCer, the latter being detected in 4 out of 6 specimens with sulfoglycolipids. The expression of sulfatide and sulfated LacCer was found to be positively correlated with the amounts of GalCer and LacCer as substrates for sulfotransferase and expression of the genes for GalCer sulfotransferase and ceramide galactosyltransferase. Sulfoglycolipids in ovarian carcinoma tissues were revealed to be expressed in morphologically defined type-characteristic manners, in contrast to the ubiquitous distribution of GM3.

Association of pancreatic adenocarcinoma up-regulated factor expression in ovarian mucinous adenocarcinoma with poor prognosis.

Pancreatic adenocarcinoma up-regulated factor (PAUF) expression is elevated in both ovarian tumors and pancreatic adenocarcinoma. However, PAUF expression in ovarian tumors according to histologic subtype and grade has not been investigated. In this study, we examined various clinicopathologic features of 24 patients with mucinous cystadenoma (MCA), 36 with mucinous borderline tumors (MBTs), and 46 with mucinous adenocarcinomas (MACs) according to PAUF expression status assessed using immunohistochemistry. We found that MACs more frequently stained positive for PAUF than did MCAs and MBTs (P < 0.0001). Although there was no significant differences with respect to other clinicopathologic characteristics of MACs according to PAUF expression status, patients with PAUF-weakly positive and PAUF-strongly positive MACs tended to have a shorter overall survival (OS) than those with PAUF-negative MAC, determined using a Kaplan-Meier analysis (P = 0.1885). After adjusting for various clinicopathologic parameters, PAUF positivity of MACs was a significant predictive factor for disease-free survival (DFS) (negative vs. weakly positive: P = 0.045, hazard ratio [HR] = 57.406, 95% confidence interval [CI]: 1.090-3022.596; and negative vs. strongly positive: P = 0.034, HR = 97.890, 95% CI: 1.412-6785.925). In conclusion, PAUF was more frequently expressed in MAC than in its benign and borderline counterparts, and was associated with a poor OS and DFS in MAC patients. Therefore, we suggest that PAUF may be a practical biomarker for histopathological categorization and a prognostic marker for patients with an ovarian mucinous tumor.

Activated wnt signaling in stroma contributes to development of pancreatic mucinous cystic neoplasms.

BACKGROUND & AIMS: Pancreatic mucinous cystic neoplasm (MCN), a cystic tumor of the pancreas that develops most frequently in women, is a potential precursor to pancreatic ductal adenocarcinoma. MCNs develop primarily in the body and tail of the pancreas and are characterized by the presence of a mucinous epithelium and ovarian-like subepithelial stroma. We investigated the involvement of Wnt signaling in KRAS-mediated pancreatic tumorigenesis and development of MCN in mice, and Wnt activation in human MCN samples. METHODS: LSL-Kras(G12D), Ptf1a-cre mice were crossed with elastase-tva mice to allow for introduction of genes encoded by the replication-competent avian sarcoma-leukosis virus long-terminal repeat with splice acceptor viruses to pancreatic acinar cells and acinar cell progenitors, postnatally and sporadically. Repeat with splice acceptor viruses that expressed Wnt1 were delivered to the pancreatic epithelium of these mice; pancreatic lesions were analyzed by histopathology and immunohistochemical analyses. We analyzed levels of factors in Wnt signaling pathways in 19 MCN samples from patients. RESULTS: Expression of Wnt1 in the pancreatic acinar cells and acinar cell progenitors of female mice led to development of unilocular or multilocular epithelial cysts in the pancreas body and tail, similar to MCN. The cystic lesions resembled the estrogen receptor- and progesterone receptor-positive ovarian-like stroma of MCN, but lacked the typical mucinous epithelium. Activated Wnt signaling, based on nuclear localization of ß-catenin, was detected in the stroma but not cyst epithelium. Wnt signaling to ß-catenin was found to be activated in MCN samples from patients, within the ovarian-like stroma, consistent with the findings in mice. CONCLUSIONS: Based on studies of mice and pancreatic MCN samples from patients, the canonical Wnt signaling pathway becomes activated and promotes development of the ovarian-like stroma to contribute to formation of MCNs.

Expression of deleted in liver cancer 1 and plasminogen activator inhibitor 1 protein in ovarian carcinoma and their clinical significance.

BACKGROUND: The deleted in liver cancer 1 (DLC1) and plasminogen activator inhibitor 1 (PAI-1) are known to be closely associated with tumor growth and metastasis in several kinds of human tumors. The aim of this study was to investigate the expression of DLC1 and PAI-1 in ovarian carcinoma, and evaluate their relations with the prognosis of ovarian carcinoma. METHODS: Immunohistochemical staining and Western blot were used to examine the expressions of DLC1 and PAI-1 protein in 25 specimens normal ovarian tissues, 52 specimens of serous cystadenocarcinoma tissues and 23 specimens of mucinous cystadenocarcinoma tissues. Chi-square test, Logistic regression and Partial Correlate analysis were performed to evaluate the association between DLC1 and PAI-1 with clinicopathological characteristics. Overall survival was estimated by Kaplan-Meier curves and multivariate Cox analysis. The relationships between DLC1 and PAI-1 protein expression were analyzed by Pearson's correlation coefficient. RESULTS: The expression of DLC1 protein in ovarian carcinoma tissues was significantly lower than that in normal ovarian tissues, but it was converse for PAI-1. In ovarian carcinoma, the expression of DLC1 was significantly associated with advanced FIGO stage, ascites and positive lymph node metastasis, whereas PAI-1 protein was closely related with advanced FIGO stage, poor histological differentiation and lymph node metastasis. The expression of DLC1 was negatively correlated with PAI-1 in ovarian carcinoma. Ovarian cancer patients with negative expression of DLC1 and positive expression of PAI-1 had the worst overall survival time compared to other patients. CONCLUSIONS: The expression of DLC1 and PAI-1 were closely related with the metastasis and invasion of ovarian carcinoma, only the combination of DLC1 and PAI-1 could serve as an independent prognostic factor of ovarian carcinoma.

Claudin-18 overexpression in intestinal-type mucinous borderline tumour of the ovary.

AIMS: Mucinous borderline tumours of the ovary are subclassified as intestinal-type (IMBT) and endocervical-like (EMBT), which differ in their clinicopathological features. In this study, we attempted to elucidate characteristics of the mucinous epithelium in each subtype. METHODS AND RESULTS: The expression of claudin-18, a marker of gastric differentiation, MUCs, CDX2, CK7, CK20, oestrogen receptor (ER), progesterone receptor (PgR), CA-125 and vimentin in IMBTs (n = 54), EMBTs (n = 25) and serous borderline tumours (SBTs) (n = 22) were compared by immunohistochemistry. Claudin-18 positivity was identified in 98% of the IMBTs, whereas only 4% of the EMBTs were claudin-18-positive. Expression of intestinal markers such as CDX2 and MUC2 was relatively infrequent in IMBTs (48% and 33%, respectively). Müllerian-lineage markers such as ER, PgR and vimentin were expressed rarely in IMBTs, while most EMBTs and SBTs were positive for these markers. Hierarchial clustering revealed a close association between EMBTs and SBTs, while IMBTs were clearly separate. CONCLUSIONS: Claudin-18 positivity is a specific phenotype that is characteristic of IMBTs. Frequent and diffuse expression of gastric markers, along with less frequent and usually focal expression of intestinal markers, suggests that IMBTs are essentially composed of gastrointestinal-type mucinous epithelium (gastric-type epithelium with a variable degree of intestinal differentiation).

Mucinous myoepithelioma, a recently described new myoepithelioma variant.

Myoepithelial neoplasms are tumors composed almost exclusively of cells with myoepithelial differentiation. They frequently contain spindle, plasmacytoid or epithelioid shaped cells and may have oncocytic or clear cytoplasmic features. They are uncommon, accounting for 1.5 % of all salivary gland tumors and for 2.2-5.7 % of major and minor salivary gland tumors, respectively. Recently this author, together with several colleagues, have described three unusual myoepithelial tumors, two benign and one malignant that contained abundant intracellular mucin material, which they termed the mucinous variant of myoepithelioma. This represents a unique, previously undescribed subtype that does not fit in the current classification system. A literature review revealed several similar cases reported as "signet ring-cell" adenocarcinomas of salivary gland, which stained for myoepithelial markers, in addition to containing intracellular mucin material, that are more accurately classified as mucinous myoepithelioma. To date, there are 17 reported mucinous myoepitheliomas; four were classified as benign and 13 as malignant. Thirteen arose in minor salivary glands and four in the parotid gland. One patient presented with a lymph node metastasis. With minimal follow-up currently available, this appears to be a benign to low-grade malignancy.

Metabolomic-derived novel cyst fluid biomarkers for pancreatic cysts: glucose and kynurenine.

BACKGROUND: Better pancreatic cyst fluid biomarkers are needed. OBJECTIVE: To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers. DESIGN: Retrospective study. SETTING: Tertiary-care referral center. PATIENTS: Two independent cohorts of patients (n = 26 and n = 19) with histologically defined pancreatic cysts. INTERVENTION: Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed. MAIN OUTCOME MEASUREMENTS: Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve). RESULTS: Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P = .002, validation P = .006; and kynurenine first cohort P = .002, validation P = .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts. LIMITATIONS: Small sample sizes. CONCLUSION: Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas.

Expression of urokinase plasminogen activator and plasminogen activator inhibitor type-1 in ovarian cancer and its clinical significance.

The urokinase plasminogen activator system, which consists of urokinase plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1) and urokinase plasminogen activator receptor (uPAR), plays an important role in tumor invasion and metastasis, and it may be a potential diagnostic biomarker and therapeutic target in cancer. It has been found that the expression of uPA and PAI-1 in ovarian cancer is related to clinical pathologies, while their effects on the biological behavior of tumor cells and their clinical significance are still unknown. In this study, 100 tissue samples (60 samples from malignant tumors, 20 from benign tumors and 20 from controls) and 147 blood samples (49 samples each from patients with malignant tumors, benign tumors and control group, respectively) were analyzed. The positive expression levels of uPA and PAI-1 in the malignant tumor samples and their serum concentrations in the malignant group were all significantly higher than these levels in the benign tumors and controls. In addition, the levels in patients with poorly differentiated and stage III-IV cancers, cancers with metastases as well as residual tumors >2 cm after surgery, were all obviously increased, consistent with their concentrations in serum. The Cox model analysis showed that expression of uPA at the transcription level had significant associations with prognosis. In addition, uPA greatly enhanced the abilities of cell invasion, migration and adhesion through its overexpression in SKOV3 cells. Collectively, our results showed that uPA and PAI-1 play important roles in ovarian cancer development; therefore, their expression in tissues and their concentrations in serum would greatly assist the diagnosis and prediction of the prognosis in ovarian cancer.