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Background MicroRNA (miRNA) expression is known to be deregulated in cervical carcinomas. However, no data is available about the miRNA expression pattern for the minimal deviation adenocarcinoma (MDA) of uterine cervix. We sought to detect deregulated miRNAs in MDA in an attempt to find the most dependable miRNA or their combinations to understand their tumorigenesis pathway and to identify diagnostic or prognostic biomarkers. We also investigated the association between those miRNAs and their target genes, especially Notch1 and Notch2. Methods We evaluated miRNA expression profiles via miRNA microarray and validated them using.real-time PCR assays with 24 formalin-fixed, paraffin-embedded tissue blocks of MDA and 11 normal proliferative endocervical tissues as control. Expression for Notch1 and 2 was assessed by immunohistochemistry. Results MiRNA-135a-3p, 192-5p, 194-5p, and 494 were up-regulated, whereas miR-34b-5p, 204-5p, 299-5p, 424-5p, and 136-3p were down-regulated in MDA compared with normal proliferative endocervical tissues (all P <0.05). Considering the second-order Akaike Information Criterion consisting of likelihood ratio and number of parameters, miR-34b-5p showed the best discrimination power among the nine candidate miRNAs. A combined panel of miR-34b-5p and 194-5p was the best fit model to discriminate between MDA and control, revealing 100% sensitivity and specificity. Notch1 and Notch2, respective target genes of miR-34b-5p and miR-204-5p, were more frequently expressed in MDA than in control (63% vs. 18%; 52% vs. 18%, respectively, P <0.05). MiR-34b-5p expression level was higher in Notch1-negative samples compared with Notch1-positive ones (P <0.05). Down-regulated miR-494 was associated with poor patient survival (P =0.036). Conclusions MDA showed distinctive expression profiles of miRNAs, Notch1, and Notch2 from normal proliferative endocervical tissues. In particular, miR-34b-5p and 194-5p might be used as diagnostic biomarkers and miR-494 as a prognostic predictor for MDA. The miR-34b- 5p/Notch1 pathway as well as Notch2 might be important oncogenic contributors to MDA. [ABSTRACT FROM AUTHOR]

Background: Extensive evidence has accumulated regarding the role of mesenchymal stromal cells (MSCs) in tumor progression, but the exact effects and mechanisms underlying this role remain unclear. We investigated the effects of MSC-associated tumor progression in MSC-sarcoma models and a gastric cancer metastatic model. Methods: We conducted an in vitro growth kinetics assay and an in vivo tumor progression assay for sarcoma cells and gastric cancer cells in the presence or absence of MSCs. Results: MSC-cocultured human fibrosarcoma cells (HT1080) showed accelerated growth compared with HT1080 alone (79- vs 37-fold change, p<.050). For HT1080, human MSC-coinjected tumors showed significantly greater and highly infiltrative growth compared to those of HT1080 alone (p=.035). For mouse fibrosarcoma cells (WEHI164), mouse MSC-coinjected tumors had greater volume than those of WEHI164 alone (p=.141). For rat sarcoma cells (RR1022), rat MSC-coinjected tumors exhibited greater volume and infiltrative growth than those of RR1022 alone (p=.050). For human gastric cancer cells (5FU), tumors of 5FU alone were compact, nodular in shape, and expansile with good demarcation and no definite lung metastatic nodules, whereas tumors grown in the presence of human MSCs showed highly desmoplastic and infiltrative growth and multiple lung metastasis. Conclusions: We observed morphological evidence for MSC-associated tumor progression of fibrosarcomas and gastric cancer cells. [ABSTRACT FROM AUTHOR]

Background: The tall cell variant of papillary thyroid carcinoma (TCVPTC) is more aggressive than classic papillary thyroid carcinoma (PTC), but the percentage of tall cells needed to diagnose TCVPTC remains controversial. In addition, little is known about the clinicopathologic features of classic PTC with tall cell features (TCF). Methods: We retrospectively selected and reviewed the clinicopathologic features and presence of the BRAF mutation in 203 cases of classic PTC, 149 cases of classic PTC with TCF, and 95 cases of TCVPTCs, which were defined as PTCs having <10%, 10-50%, and ⩾50% tall cells, respectively. Results: TCVPTCs and classic PTCs with TCF did not vary significantly in clinicopathologic characteristics such as pathologic (p) T stage, extrathyroidal extension, pN stage, lateral lymph node metastasis, or BRAF mutations; however, these features differed significantly in TCVPTCs and classic PTCs with TCF in comparison to classic PTCs. Similar results were obtained in a subanalysis of patients with microcarcinomas (⩽1.0 cm in size). Conclusions: Classic PTCs with TCF showed a similar BRAF mutation rate and clinicopathologic features to TCVPTCs, but more aggressive characteristics than classic PTCs. [ABSTRACT FROM AUTHOR]

Background/Aims: A single gene mutation alone cannot explain the poor prognosis of colorectal cancer. This study aimed to establish a correlation between the expression of six proteins and the prognosis of colorectal cancer patients. Methods: Tissue samples were collected from 266 patients who underwent surgery for colorectal cancer at our institution from January 2006 to December 2007. The expression of six proteins were determined using immunohistochemical staining of specimens. Results: Cathepsin D, p53, COX-2, epidermal growth factor receptor, c-erbB-2, and Ki-67 expression were detected in 38.7%, 60.9%, 37.6%, 35.7%, 30.1%, and 74.4% of the samples, respectively. The expression of cathepsin D was significantly correlated with reduced cancer-free survival (p=0.036) and colorectal cancer-specific survival (p=0.003), but the other expression levels were not. In a multivariate analysis, cathepsin D expression was found to be an independent prognostic factor for poorer colorectal cancer-specific survival (hazard ratio, 8.55; 95% confidence interval, 1.07 to 68.49). Furthermore, patients with tumors expressing four or more of the proteins had a significantly decreased cancer-free survival rate (p=0.006) and colorectal cancer-specific survival rate (p=0.002). Conclusions: Patients with cathepsin D positivity had a poorer outcome than patients who were cathepsin D-negative. Thus, cathepsin D may provide an indicator for appropriate intensive follow-up and adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The microtubule-associated protein Tau binds to both inner and outer surfaces of microtubules, leading to tubulin assembly and microtubule stabilization. The aim of this study was to evaluate the significance of Tau, α-tubulin, and βIII-tubulin expression in breast carcinoma and to assess their relationships with disease progression in the context of taxane treatment. Methods: Immunohistochemical expressions of Tau, α-tubulin, and βIII-tubulin were assessed in 183 breast cancer cases. Expression was correlated with clinicopathologic parameters, disease progression and overall survival. Results: Tau expression was correlated with lymph node metastasis and estrogen receptor (ER) positivity (p=.003 and p<.001, respectively). Loss of α-tubulin was significantly correlated with distant metastasis (p=.034). Loss of βIII-tubulin was correlated with lymph node metastasis and ER positivity (p=.004 and p<.001, respectively). In taxanetreated cases, Tau expression and loss of α-tubulin and βIII-tubulin expression were related to disease progression (p=.001, p=.028, and p=.030, respectively). Tau expression was associated with a worse survival rate in taxane-treated patients (p=.049). Conclusions: Tau expression and loss of α-tubulin and βIII-tubulin expression were correlated with aggressive behavior in taxane- treated breast cancer. Further evaluation of Tau, α-tubulin and βIII-tubulin may be useful in predicting clinical behavior and seeking therapeutic measures in taxane-based chemotherapy for breast cancer. [ABSTRACT FROM AUTHOR]

Objective : Intracranial hemangiopericytomas (HPCs) are rare tumors with aggressive behavior, including local recurrence and distant metastasis. We conducted this retrospective study to evaluate the efficacy of grossly total resection and adjuvant radiotherapy (RT) for these tumors. Methods : A total of 13 patients treated for intracranial HPC from January 1995 through May 2013 were included in this retrospective study. We analyzed the clinical presentations, radiologic appearances, treatment results, and follow-up outcomes, as well as reviewed other studies. Results : The ages of the patients at the time of diagnosis ranged from 26 to 73 years (mean : 48 years). The majority of the patients were male (92.3%), and the majority of the tumors were located in the parasagittal and falx. The ratio of intracranial HPCs to meningiomas was 13 : 598 in same period, or 2.2%. Seven patients (53.8%) had anaplastic HPCs. Nine patients (69.2%) underwent gross total tumor resection in the first operation without mortality. Eleven patients (84.6%) underwent postoperative adjuvant RT. Follow-up period ranged from 13 to 185 months (mean : 54.3 months). The local recurrence rate was 46.2% (6/13), and there were no distant metastases. The 10-year survival rate after initial surgery was 83.9%. The initial mean Karnofsky performance scale (KPS) was 70.8 and the final mean KPS was 64.6. Conclusion : Gross total tumor resection upon initial surgery is very important. We believe that adjuvant RT is helpful even with maximal tumor resection. Molecular biologic analyses and chemotherapy studies are required to achieve better outcomes in recurrent intracranial HPCs. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate a newly-developed EASYPREP liquidbased cytology method in cervicovaginal specimens and compare it with SurePath. Methods: Cervicovaginal specimens were prospectively collected from 1,000 patients with EASYPREP and SurePath. The specimens were first collected by brushing for SurePath and second for EASYPREP. The specimens of both methods were diagnosed according to the Bethesda System. Additionally, we performed to REBA HPV-ID genotyping and sequencing analysis for human papillomavirus (HPV) on 249 specimens. Results: EASYPREP and SurePath showed even distribution of cells and were equal in cellularity and staining quality. The diagnostic agreement between the two methods was 96.5%. Based on the standard of SurePath, the sensitivity, specificity, positive predictive value, and negative predictive value of EASYPREP were 90.7%, 99.2%, 94.8%, and 98.5%, respectively. The positivity of REBA HPV-ID was 49.4% and 95.1% in normal and abnormal cytological samples, respectively. The result of REBA HPV-ID had high concordance with sequencing analysis. Conclusions: EASYPREP provided comparable results to SurePath in the diagnosis and staining quality of cytology examinations and in HPV testing with REBA HPV-ID. EASYPREP could be another LBC method choice for the cervicovaginal specimens. Additionally, REBA HPV-ID may be a useful method for HPV genotyping. [ABSTRACT FROM AUTHOR]

Background/Aims: To investigate the gastroprotective effects of grape seed proanthocyanidin extracts (GSPEs) against nonsteroid anti-inflammatory drug (NSAID)-induced gastric mucosal injury in rats. Methods: Sprague-Dawley rats were randomly allocated to the normal control, indomethacin, low-dose GSPE, high-dose GSPE and misoprostol groups. All groups except the normal control group received pretreatment drugs for 6 consecutive days. On the 5th and 6th day, indomethacin was administered orally to all groups except for normal control group. The microscopic features of injury were analyzed. The levels of gastric mucosal glutathione, gastric mucosal prostaglandin E2 (PGE2), and proinflammatory cytokines were investigated. Results: The total areas of ulceration in the GSPE and misoprostol groups were significantly decreased compared with the indomethacin group (p<0.05). However, a difference in ulcer formation among the drug treatment groups was not observed. Meanwhile, the glutathione levels in the high-dose GSPE group were higher than those of both the indomethacin and misoprostol groups (p<0.05) and were similar to those of the normal control group. Additionally, there was no difference among the groups in the levels of gastric mucosal PGE2 and proinflammatory cytokines. Conclusions: High-dose GSPE has a strong protective effect against NSAID-induced gastric mucosal injury, which may be associated with the antioxidant effects of GSPE. [ABSTRACT FROM AUTHOR]

This study presents sensitive high-resolution ion microprobe (SHRIMP) U-Pb zircon ages, K-Ar ages, and whole-rock chemical and isotopic (Sr-Nd) compositions of the Early Cretaceous igneous activity in western South Korea. The volcanics and plutons yield zircon U-Pb ages of ca. 110 Ma, in the Albian of the late Early Cretaceous. K-Ar biotite and plagioclase ages are slightly younger, ca. 103 Ma. The geochemical signatures of the rocks are characterized by negative Nb, Ta, and Ti anomalies, relatively low ∊Nd(T) values (between -15.91 and -9.36), and enrichment in light rare earth elements, suggesting the effects of subduction-related magmatism. Together with the Sr and Nd isotopic compositions of the intermediate to acid volcanics, geochemical characteristics reflect a lower-crustal magma source. This Albian event over the Korean Peninsula is related to Early Jurassic subduction and subsequent lithospheric delamination and/or slab rollback after the Early Cretaceous amalgamation between the North China Block (e.g., China, Korea, and Japan) and the paleo-Eurasia continent. This postorogenic event was accompanied by the initial formation of voluminous igneous activity and subsequent basin formation at about 130-110 Ma. Crustal relaxation during this stage should be related to this postorogenic event and is attributed to paleo-Pacific Plate subduction. This result provides important clues for the Cretaceous tectonic evolution of Northeast Asia in the context of plate convergence [ABSTRACT FROM AUTHOR]

Objective: To determine whether invasion of the pharyngeal constrictor muscle in early squamous cell carcinoma of the tonsil is correlated with lymph node metastasis. Design: Retrospective analysis of medical records and pathology specimens. Setting: Tertiary care referral center. Patients: Forty-eight patients who were diagnosed as having T2 squamous cell carcinoma of the tonsil and who underwent surgery. They were divided into 2 groups: an invasive group with invasion of the pharyngeal constrictor muscle and a noninvasive group without invasion of the pharyngeal constrictor muscle. Main Outcome Measures: Comparison of regional metastasis, 5-year locoregional recurrence, and 5-year disease- specific survival between the 2 groups. Results: Invasion of the pharyngeal constrictor muscle was found in 36 patients (75%) with T2 squamous cell carcinoma of the tonsil. The rate of lymph node metastasis, the mean (SD) number of positive nodes, and the mean (SD) lymph node density were 81%, 5.47 (9.27), and 0.15 (0.22) in the invasive group, respectively, and 50%, 1.33 (1.72), and 0.04 (0.04) in the noninvasive group, respectively (P=.04, P=.02, and P=.01, respectively). Five-year locoregional recurrence was significantly correlated with invasion of the pharyngeal constrictor muscle (P=.05) and with multiple lymph node metastasis (⩾5 nodes) (P=.04) in the univariate analyses. No factor was correlated with 5-year locoregional recurrence in the multivariate analysis. Five-year diseasespecific survival was significantly correlated with multiple lymph node metastasis (⩾5 nodes) in the univariate analyses (P=.009). Five-year disease-specific survival was not significantly correlated with any clinicopathological factor in the multivariate analysis. Conclusion: Higher risk for multiple lymph node metastasis and 5-year locoregional recurrence seems to be predicted in patients with extratonsillar invasion of the pharyngeal constrictor muscle, even in early squamous cell carcinoma of the tonsil. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) is known to cause of oropharyngeal squamous cell carcinoma (SqCC). HPV positive SqCCs overexpress p16 and are associated with better survival. Several markers of cell cycles and apoptosis have been reported as a prognostic value. We examined the prognostic value of HPV status, p16, cyclin D1, and Bcl-2 in patients with tonsillar SqCC. Methods: Tissue microarrays were constructed in 56 cases of tonsillar SqCC for which we performed an immunohistochemistry and an in situ hybridization (ISH) of the HPV. Results: Of the 56 cases, 31 (55.3%) were positive for p16 and 20 (35.7%) were positive for HPV ISH. The expressions of p16, cyclin D1, and Bcl-2 were not correlated with the clinicopathologic variables including smoking status, differentiation and pT- and pN-stages. The HPV ISH positive group showed a better overall survival than the HPV negative group (p=0.04), and the p16 positive group showed a better disease free survival (DFS) than the negative group (p=0.016). Cox regression analysis showed that only p16 positivity was an independent prognostic factor for DFS (p=0.03; hazard ratio, 10.1). Conclusions: Our results indicate that both p16 expression and HPV status are useful indicators for risk stratification in patients with tonsillar SqCC. [ABSTRACT FROM AUTHOR]

A male infant presented with bilateral scrotal masses 7 months after removal of an immature gastric teratoma. After surgical excision, histology showed gliomatosis peritonei. We report an unusual presentation of gliomatosis peritonei arising from a rare lesion of immature gastric teratoma. [ABSTRACT FROM AUTHOR]

Background: Oncoprotein HCCR-1 functions as a negative regulator of the p53 and contributes breast tumorigenesis. The serum HCCR-1 assay is useful in diagnosing breast cancer and mice transgenic for HCCR developed breast cancers. But it is unknown how HCCR-1 contributes to human breast tumorigenesis. Methods: Oncogene HCCR-1 expression levels were determined in normal breast tissues, breast cancer tissues and cancer cell lines. We examined whether HCCR-1 protein expression in breast cancer is related to different biological characteristics, including ER, PR, p53 genotype, and HER2 status in 104 primary breast cancer tissues using immunohistochemical analyses. Results: HCCR-1 was upregulated in breast cancer cells and tissues compared with normal breast tissues. In this study, overexpression of HCCR-1 was well correlated with known breast cancer prognostic markers including the presence of steroid receptors (ER and PR), p53 mutation and high HER2 overexpression. HCCR-1 was not detected in the ER-negative, PR-negative, p53 negative and low HER2 breast cancer tissues. These data indicate that the level of HCCR-1 in breast cancer tissues is relatively well correlated with known breast cancer factors, including the HER2 overexpression, p53 mutation, and ER/PR status. Conclusion: Determination of HCCR-1 levels as options for HER2 testing is promising although it needs further evaluation. [ABSTRACT FROM AUTHOR]

Cutaneous bronchogenic anomalies are very rare, and we report a child who presented with mucoid discharge from a small opening on her epigastrium that was present since birth. Diagnosis and treatment of congenital bronchogenic anomalies are important because surgical excision is needed to prevent the potential risk of infection and malignant degeneration. To the best to our knowledge, this is the first report of a congenital bronchogenic sinus of the abdominal wall. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid microcarcinoma (PTMC) detection has been increasing explosively with the recent improvement and application of new diagnostic tools. However, the associations between clinical, histopathological, and molecular findings are often not fully evaluated in reaching a decision for the treatment of PTMC. Objective: To retrospectively evaluate the patients diagnosed with PTMC in terms of the clinical and histopathological features and the immunohistochemical findings of specific molecular markers, and thereby provide an association with the disease prognosis for the Korean patients. Design: We have reviewed the clinical records of patients who underwent surgery for thyroid cancer (during January 2000 to August 2006 interval) at St. Mary''s Hospital, Seoul, Korea. The clinical and histopathological characteristics of 217 PTMCs were evaluated cross-sectionally after surgery, and immunohistochemical staining of p53, epidermal growth factor receptor (EGFR), Ki-67, and cyclooxygenase-2 (COX-2) for 87 isolated specimens was performed. Main outcome: The proportions of extrathyroid extension, lymphatic invasion, and lymph node metastasis cited were 31.9, 19.2, and 17.8, respectively. However, distant metastasis was not noted. Fifty-three (27.1) patients had multiplicity, and 39 patients (20.0) had bilateral disease. A primary tumor larger than 5 mm was significantly associated with extrathyroid extension, lymphatic invasion, and lymph node metastasis. The absence of EGFR expression shown by immunohistochemical analysis was closely correlated with extrathyroid extension and lymph node metastasis, while the absence of COX-2 expression was associated with multiplicity and bilaterality. Conclusion: Many patients with PTMC had clinical and histopathological poor prognostic factors. The expression of molecular markers, such as EGFR and COX-2, may have a role in the prognosis of PTMC. When considering all of the prognostic factors, a more tailored management approach appears to be necessary for patients with PTMC. [ABSTRACT FROM AUTHOR]

Objective:We analyzed the sonographic characteristics of thyroid nodules and assessed the diagnostic value of ultrasonography in order to distinguish between benign and malignant lesions in terms of the management of thyroid nodules. Design:We retrospectively analyzed the sonographic features of thyroid nodules in 580 patients who had been examined with fine-needle aspiration cytology or who underwent surgery for a thyroid nodule. The sonographic features that suggested malignancy include microcalcifications, an irregular or microlobulated margin, marked hypoechogenicity, and a shape that was taller than it was wide. The presence of one or more of these features indicated classification as category 3 (malignant). The absence of all of these features indicated classification as category 2 (benign). Presence of an anechogenic cystic nodule was classified as category 1 (benign). Main outcome:Of 124 lesions classified as category 3, 60 of the lesions were malignant. Of 418 lesions classified as category 1 or 2, 409 were benign. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy based on the sonographic classification method were 87.0, 86.5, 48.4, 97.8, and 86.5, respectively. Conclusions:Our results identified this sonographic classification as a useful tool in the differentiation of malignant nodules from benign nodules. In view of the high negative predictive value of sonographic classification, a more aggressive approach is recommended only for category 3 nodules. [ABSTRACT FROM AUTHOR]

Transgenic mice containing novel oncogene HCCR-2 were generated to analyse the phenotype and to characterize the role of HCCR-2 in cellular events. Mice transgenic for HCCR-2 developed breast cancers and metastasis. The level of p53 in HCCR-2 transgenic mice was elevated in most tissues including breast, brain, heart, lung, liver, stomach, kidney, spleen, and lymph node. We examined whether stabilized p53 is functional in HCCR-2 transgenic mice. Defective induction of p53 responsive genes including p21WAF1, MDM2, and bax indicates that stabilized p53 in HCCR-2 transgenic mice exists in an inactive form. These results suggest that HCCR-2 represents an oncoprotein that is related to breast cancer development and regulation of the p53 tumor suppressor.Oncogene (2004) 23, 1950-1953. doi:10.1038/sj.onc.1207356 Published online 22 December 2003 [ABSTRACT FROM AUTHOR]

The article presents the case of a 53-year-old man with esophageal squamous cell carcinoma in situ overlying leiomyoma mimicking invasive cancer. The patient underwent subtotal esophagectomy and a nodular lesion was identified. Squamous cell carcinomas and leiomyomas are common epithelial and mesenchymal tumors of the esophagus.

A letter to the editor is presented in response to the article "Prospective validation of an immunohistochemical panel (glypican 3, heat shock protein 70 and glutamine synthetase) in liver biopsies for diagnosis of very early hepatocellular carcinoma," by S. Tremosini in a 2012 issue of the journal.