Proto-oncogene Pokemon in thyroid cancer: a potential promoter of tumorigenesis in papillary thyroid carcinoma

Background@#Pokemon is an oncogenic transcription regulator that plays a critical role in cellular differentiation. Although it has been found to be overexpressed in several types of cancer involving different organs, its role in thyroid gland has yet to be reported. The objective of this study was to evaluate the expression of Pokemon in papillary thyroid carcinoma (PTC) based on clinicopathological parameters. @*Methods@#Tissue microarray samples derived from patients with PTC or benign thyroid disease were used to evaluate Pokemon expression based on immunohistochemical analysis. Correlations of its expression with various clinicopathological parameters were then analyzed. @*Results@#Pokemon expression was observed in 22.0% of thyroid follicular cells from the normal group, 44.0% from the group with benign thyroid diseases, and 92.1% from the group with PTC (p < .001). The intensity of Pokemon expression was markedly higher in the PTC group. Pokemon expression level and PTC tumor size showed an inverse correlation. T1a tumors showed strong expression levels of Pokemon. However, larger tumors showed weak expression (p = .006). @*Conclusions@#Pokemon expression is associated with tumorigenesis of PTC, with expression showing an inverse correlation with PTC tumor size. This might be related to the negative regulation of aerobic glycolysis by Pokemon.

Proto-oncogene Pokemon in thyroid cancer: a potential promoter of tumorigenesis in papillary thyroid carcinoma

Background@#Pokemon is an oncogenic transcription regulator that plays a critical role in cellular differentiation. Although it has been found to be overexpressed in several types of cancer involving different organs, its role in thyroid gland has yet to be reported. The objective of this study was to evaluate the expression of Pokemon in papillary thyroid carcinoma (PTC) based on clinicopathological parameters. @*Methods@#Tissue microarray samples derived from patients with PTC or benign thyroid disease were used to evaluate Pokemon expression based on immunohistochemical analysis. Correlations of its expression with various clinicopathological parameters were then analyzed. @*Results@#Pokemon expression was observed in 22.0% of thyroid follicular cells from the normal group, 44.0% from the group with benign thyroid diseases, and 92.1% from the group with PTC (p < .001). The intensity of Pokemon expression was markedly higher in the PTC group. Pokemon expression level and PTC tumor size showed an inverse correlation. T1a tumors showed strong expression levels of Pokemon. However, larger tumors showed weak expression (p = .006). @*Conclusions@#Pokemon expression is associated with tumorigenesis of PTC, with expression showing an inverse correlation with PTC tumor size. This might be related to the negative regulation of aerobic glycolysis by Pokemon.

Prognostic Significance of the Expression of Claudin-1 in Head and Neck Squamous Cell Carcinoma / 대한이비인후과학회지

Background and Objectives@#Claudin-1 (CLDN-1) is the major component of tight junctions and functions in controlling cell to cell adhesion. Certain claudins were expressed aberrantly and proved to have prognostic significance in various human cancers. However, its clinical significance has been poorly understood in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to investigate the relationship between CLDN-1 expression and clinicopathologic parameters in HNSCC.Subjects and Method The surgical specimens of primary HNSCCs from a consecutive cohort of 91 patients were retrospectively collected. Immunohistochemical staining for CLDN-1 was performed blindly by two pathologists. CLDN-1 staining intensity was scored semi-quantitatively on a scale of 0 to 3 (0: negative; 1: weak; 2: moderate; 3: strong). For the statistical analysis, the expression levels were classified as low (negative and weak) and high (moderate and strong). Next, the association between CLDN-1 expression and clinicopathological features & clinical outcomes was analyzed. @*Results@#The increased CLDN-1 expression was significantly associated with lymphatic invasion (p=0.019). The expression level of CLDN-1 was not associated with pathological T stage, lymph node metastasis or recurrence. Kaplan-Meier analysis found that 3-year overall survival (OS) rate was 53% in patients with high level CLDN-1 expression and 74% in patients with low level CLDN-1 expression. It also found that 5-year OS rate was 49% in patients with high level CLDN-1 expression and 68% in patients with low level CLDN-1 expression. A significantly poor OS rate was recorded in patients with high level of CLDN-1 expression compared to patients with low level CLDN-1 expression (p=0.022). @*Conclusion@#CLDN-1 may serve as useful prognostic marker in patients with HNSCCs.

Kallikrein 5 overexpression is associated with poor prognosis in uterine cervical cancer / 부인종양

Objective@#Kallikrein 5 (KLK5), which is frequently observed in normal cervico-vaginal fluid, is known to be related to prognosis in several solid tumors. We investigated the prognostic significance of KLK5 in uterine cervical cancer using tumor tissue microarray and immunohistochemistry staining. @*Methods@#We analyzed samples of 165 patients with uterine cervical cancer who received definitive radiation therapy between 2004 and 2012. We divided patients into two groups stratified by their KLK5 activity by immunohistochemistry staining: negative/weak (0–1+) (n=120 patients) and moderate/strong (2–3+) group (n=45 patients). Patient and tumor characteristics, patterns of failure, and survival outcomes were compared. Univariable and multivariable analyses were performed to identify prognostic factors. @*Results@#Patients with KLK5 2–3+ were younger (median: 52 vs. 60 years) and had frequent paraaortic lymph node involvement (40.0% vs. 18.3%) than those with KLK5 0–1+. With a median follow-up of 60.8 (interquartile range, 47.5–77.9) months, patients with KLK5 2–3+ had inferior 5-year locoregional recurrence-free survival and distant metastasis-free survival of 61.7% (vs. 77.5% in KLK5 0–1+ group) and 59.4% (vs. 72.8% in the KLK5 0–1+ group), respectively (all p<0.05). KLK5 2–3+ expression retained its significance after adjusting for other well-known prognostic factors of tumor size and stage in multivariable analysis. @*Conclusions@#KLK5 overexpression is associated with the aggressiveness of cervical cancer and may underlie the diminished response to conventional treatments. Therefore, KLK5 could be a reliable prognostic factor in cervical cancer.

Kallikrein 5 overexpression is associated with poor prognosis in uterine cervical cancer / 부인종양

Objective@#Kallikrein 5 (KLK5), which is frequently observed in normal cervico-vaginal fluid, is known to be related to prognosis in several solid tumors. We investigated the prognostic significance of KLK5 in uterine cervical cancer using tumor tissue microarray and immunohistochemistry staining. @*Methods@#We analyzed samples of 165 patients with uterine cervical cancer who received definitive radiation therapy between 2004 and 2012. We divided patients into two groups stratified by their KLK5 activity by immunohistochemistry staining: negative/weak (0–1+) (n=120 patients) and moderate/strong (2–3+) group (n=45 patients). Patient and tumor characteristics, patterns of failure, and survival outcomes were compared. Univariable and multivariable analyses were performed to identify prognostic factors. @*Results@#Patients with KLK5 2–3+ were younger (median: 52 vs. 60 years) and had frequent paraaortic lymph node involvement (40.0% vs. 18.3%) than those with KLK5 0–1+. With a median follow-up of 60.8 (interquartile range, 47.5–77.9) months, patients with KLK5 2–3+ had inferior 5-year locoregional recurrence-free survival and distant metastasis-free survival of 61.7% (vs. 77.5% in KLK5 0–1+ group) and 59.4% (vs. 72.8% in the KLK5 0–1+ group), respectively (all p<0.05). KLK5 2–3+ expression retained its significance after adjusting for other well-known prognostic factors of tumor size and stage in multivariable analysis. @*Conclusions@#KLK5 overexpression is associated with the aggressiveness of cervical cancer and may underlie the diminished response to conventional treatments. Therefore, KLK5 could be a reliable prognostic factor in cervical cancer.

Synchronous Presentation of Ductal Carcinoma In Situ of the Breast with Follicular Lymphoma

A synchronous incidence of breast cancer and follicular lymphoma (FL) is uncommon. The association between these two conditions could be explained by the antigenic stimulation of the adjacent carcinoma and common genetic background. This study aimed to review the literature, and discuss the etiology and management of synchronous breast cancer and FL. Herein, we presented a case of synchronous ductal carcinoma in situ (DCIS) of the breast and FL involving multiple lymph nodes, including those in both axilla. A 49-year-old woman presented with palpable lumps in both axilla. She underwent lumpectomy, radiotherapy, and hormonal therapy for DCIS, while adjuvant chemotherapy was recommended for the lymphoma. Diagnosis was based on histopathologic analysis, such as excision or biopsy.

Predictors for the Transition from Ductal Carcinoma In Situ to Invasive Breast Cancer in Korean Patients

PURPOSE: To identify predictive factors of upstaging from diagnosed ductal carcinoma in situ (DCIS) to invasive cancer after surgical excision. METHODS: One hundred seventy-four patients diagnosed with DCIS based on biopsies between January 2009 and December 2014 were evaluated. Patients' clinicopathological variables were assessed to identify predictive factors of invasive carcinoma from final pathology. RESULTS: One hundred seventy-four cases of DCIS were included. Of these, 42 were upstaged to invasive carcinoma on the final excision. Preoperative features such as age 40 years or younger at diagnosis, presence of a palpable mass, ultrasonography (USG)-guided core needle biopsy, tumor size ≥20 mm on USG, high grade DCIS, cribriform DCIS, comedo necrosis, presence of intraluminal calcification, estrogen receptor negativity, progesterone receptor negativity and triple-negative subtype were significantly associated with the risk of invasive carcinoma. Multivariate analysis showed that a tumor size ≥20 mm on USG and triple negative subtype were independently associated with upstaging. CONCLUSION: Tumor size ≥20 mm on USG and triple-negative subtype were independently associated with the upstaging of DCIS to invasive cancer.

High Expression of Urokinase-Type Plasminogen Activator Is Associated with Lymph Node Metastasis of Invasive Ductal Carcinoma of the Breast / 한국유방암학회지

PURPOSE: In the present study, we evaluated the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) by performing immunohistochemical staining to determine whether they were reliable prognostic markers in patients with breast cancer. METHODS: Demographic and clinicopathological parameters of 214 patients with invasive ductal carcinoma (IDC) and 80 patients with ductal carcinoma in situ (DCIS) who were diagnosed and treated from 2006 to 2010 were analyzed. Tissue microarray was constructed and immunohistochemical staining was performed for each specimen. RESULTS: Univariate analyses showed that age at diagnosis, history of hormone replacement therapy, radiation therapy, skin and chest wall invasion, Paget disease, lymphovascular invasion, estrogen receptor positivity, and triple-negative subtype were significantly associated with patient prognosis (p<0.005). Patients with DCIS showed higher PAI-1 expression than patients with IDC (82.5% and 36.2%, respectively; p=0.012). Lymph node metastasis was more frequent in patients with high uPA levels than in patients with low uPA levels (p=0.001). CONCLUSION: Our results suggested that PAI-1 was involved in tumor progression in the early stages of breast cancer, such as DCIS. In addition, our results suggested that high uPA levels were associated with the lymph node metastasis of IDC.

Traumatic Bowel Perforation and Inguinal Hernia Masking a Mesenteric Calcifying Fibrous Tumor

No abstract available.

Aspergillus Tracheobronchitis and Influenza A Co-infection in a Patient with AIDS and Neutropenia

Aspergillus tracheobronchitis (AT), an unusual form of invasive pulmonary aspergillosis (IPA), is characterized by pseudomembrane formation, ulcer or obstruction that is predominantly confined to tracheobronchial tree. Hematologic malignancies, neutropenia, solid organ transplantation, chronic corticosteroid therapy and acquired immunodeficiency syndrome (AIDS) are known to be major predisposing conditions. However, since the introduction of highly active antiretroviral therapy, there is only one reported case of AT in AIDS patient. After pandemic of influenza A/H1N1 2009, there are several reports of IPA in patient with influenza and most of them received corticosteroid or immunosuppressive therapy before the development of IPA. We present a 45 year-old AIDS patient with influenza A infection who developed pseudomembranous AT without corticosteroid use or immunosuppressive therapy.

Associations between the Expression of Mucins (MUC1, MUC2, MUC5AC, and MUC6) and Clinicopathologic Parameters of Human Breast Ductal Carcinomas / 한국유방암학회지

PURPOSE: Mucins are members of the glycoprotein family expressed in benign and malignant epithelial cells. The aim of this study is to evaluate the relationships between the expression of mucins in breast ductal carcinoma and clinicopathologic parameters. METHODS: We constructed tumor microarrays based on 240 cases of invasive ductal carcinoma and 40 cases of ductal carcinoma in situ (DCIS) using formalin fixed, paraffin embedded tissues. We examined the expressions of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemistry. RESULTS: MUC1 demonstrated cytoplasmic, membranous, apical, and combinative expressions. Other mucins demonstrated cytoplasmic expression. In invasive ductal carcinoma, MUC1, MUC2, MUC5AC, and MUC6 were expressed in 93.6%, 6.2%, 4.8%, and 12.4% of cases, respectively; these rates were slightly, but not significantly, higher than observed in cases of DCIS. MUC1 expression was associated with estrogen receptor (ER) expression and negative MUC1 expression was associated with triple negativity. MUC6 expression was correlated with higher histologic grade, lymphatic invasion, lymph node metastasis, and HER2 positivity. No associations with any other clinicopathologic parameters were observed. CONCLUSION: Most invasive ductal carcinomas of the breast express MUC1, and this expression is associated with ER expression. MUC6 expression is correlated with some clinicopathologic parameters that are indicators of poor prognosis. To evaluate the role of MUC6 as a potential biomarker, further studies are warranted.

Extranodal Follicular Dendritic Cell Sarcoma with Rapid Growth in Parapharynx: A Case Report

Follicular dendritic cell sarcoma (FDCS) is a rare malignancy arising from the antigen-presenting cells in the lymph node and extranodal tissue. We describe a 31-year-old male patient who presented with a swelling of the left parapharynx. The radiologic findings showed a 4.7x4.5x1.9 cm-sized, ill-defined mass in the left parapharyngeal space. A fine-needle aspiration cytology was performed and it showed scattered, irregular, cohesive clusters of tumor cells with a spindle-to-ovoid shape with irregular contours in a background of lymphocytes. Based on these findings, a diagnosis of spindle cell neoplasm was made. The surgically resected tumor was composed of elongated, ovoid or polygonal cells showing positive immunohistochemistry for CD21, CD23, and CD35. Postoperatively, the residual tumor was observed to undergo a rapidly growth. There is an overlap in the cytologic and histologic findings between FDCS of the parapharynx and other tumors. Pathologists should therefore be aware of its characteristics not only to provide an accurate diagnosis but also to recommend the appropriate clinical management.

Extranodal Follicular Dendritic Cell Sarcoma with Rapid Growth in Parapharynx: A Case Report

Follicular dendritic cell sarcoma (FDCS) is a rare malignancy arising from the antigen-presenting cells in the lymph node and extranodal tissue. We describe a 31-year-old male patient who presented with a swelling of the left parapharynx. The radiologic findings showed a 4.7x4.5x1.9 cm-sized, ill-defined mass in the left parapharyngeal space. A fine-needle aspiration cytology was performed and it showed scattered, irregular, cohesive clusters of tumor cells with a spindle-to-ovoid shape with irregular contours in a background of lymphocytes. Based on these findings, a diagnosis of spindle cell neoplasm was made. The surgically resected tumor was composed of elongated, ovoid or polygonal cells showing positive immunohistochemistry for CD21, CD23, and CD35. Postoperatively, the residual tumor was observed to undergo a rapidly growth. There is an overlap in the cytologic and histologic findings between FDCS of the parapharynx and other tumors. Pathologists should therefore be aware of its characteristics not only to provide an accurate diagnosis but also to recommend the appropriate clinical management.

The Global Histone Modification Patterns of Osteosarcoma

BACKGROUND: Epigenetic alteration may affect a patient's prognosis by altering the development and progression of the tumor. Some recent reports have identified a correlation between histone modification and patient outcome. However, no studies have been conducted on global histone modification in osteosarcomas. METHODS: We investigated histone modification in 54 cases of osteosarcoma by performing immunohistochemical staining. The immunohistochemical expression of four histone modification markers, acetylated H4 lysine 12 (H4K12Ac), acetylated H3 lysine 18, trimethylated H3 lysine 27, and dimethylated H3 lysine 4 were evaluated. RESULTS: High H4K12Ac expression was correlated with patient age (p=0.011). However, the other histone modification markers showed no correlation with any of the clinicopathological data such as survival, tumor grade, tumor site, metastasis, age, or gender. CONCLUSIONS: Our study showed that all four histone modification markers are expressed in osteosarcoma (median expression rate, 40 to 60%). However, we did not find a correlation with the clinicopathological factors except for age. Further study to evaluate the reason for the association between H4K12Ac and patient age is needed.

Expression of Cyclooxygenase-2 and Embryonic Lethal Abnormal Vision-Like Protein HuR in Gallbladder Carcinoma

BACKGROUND: Cyclooxygenase-2 (COX-2) is an enzyme that promotes proliferation of tumor cells. HuR is a member of the family of embryonic lethal abnormal vision-like proteins. Recent studies show that cytoplasmic HuR stabilizes the mRNA of COX-2 and regulates the expression of COX-2. Moreover, cytoplasmic HuR expression is associated with a poorer prognosis for patients with some cancers. The aim of this study was to investigate the expression patterns of and the relationship between COX-2 and HuR in gallbladder carcinoma. METHODS: We analyzed COX-2 and HuR expression by immunohistochemical staining of 108 gallbladder carcinomas. RESULTS: COX-2 expression and nuclear and cytoplasmic HuR expression were seen in, respectively, 61 (56.5%), 77 (71.3%), and 4 (3.7%) cases. COX-2 and nuclear HuR were simultaneously expressed in 44 of the 108 samples without any quantitative association between the levels of each. COX-2 expression correlated with tumor stage, differentiation (based on histology), lymph node metastasis, perineural invasion, and survival. Nuclear and cytological expression of HuR did not correlate with any clinical parameters. CONCLUSIONS: COX-2 expression but not HuR may play an important role in the prognosis of patients with gallbladder carcinoma.

Correlation Between Cyclooxygenase-2 Expression and HuR Cytoplasmic Translocation of Breast Cancer

BACKGROUND: Embryonic lethal abnormal vision (ELAV)-like protein HuR is known to stabilize mRNA through binding AU-rich elements in the 3'-untranslated region. Recent studies show that HuR expression is associated with the expression of several genes including cyclooxygenase-2 (COX-2). HuR exists predominantly in the nucleus, but cytoplasmic translocation of HuR is thought to be more important for its activity. COX-2 is a well-known enzyme that promotes tumor growth. METHODS: To evaluate the correlation of HuR and COX-2 expression, we analyzed expression of HuR and COX-2 in 91 cases of breast cancer using immunohistochemistry. RESULTS: Nuclear and cytoplasmic expression of HuR was seen in 76 (83.5%) and 19 (20.9%) of 91 cases respectively. COX-2 immunoreactivity was seen in 54 (59.4%) cases. Cytoplasmic HuR expression showed significant correlation with COX-2 expression (p=0.001). Nuclear HuR showed no correlation with COX-2 expression or other clinicopathological parameters. COX-2 expression is significantly associated with tumor grade (p=0.028). COX-2 (p=0.092) and cytoplasmic (p=0.569) and nuclear HuR (p=0.247) expression showed no correlation with survival. CONCLUSIONS: These results suggest that cytoplasmic HuR expression is associated with COX-2 expression in breast cancer and cytoplasmic location of HuR might contribute to the stabilization of COX-2 mRNA.

Diagnostic Value of Urine Cytology in 236 cases; a Comparison of Liquid-Based Preparation and Conventional Cytospin Method / 대한세포병리학회지

Urine cytology is an important screening tool for urinary tract neoplasms. Liquid-based preparation methods, such as ThinPrep(R), have been introduced for non-gynecological samples. We aimed to assess the diagnostic accuracy of liquid-based preparations in urine cytology by comparing the results of the conventional Cytospin preparation method for the same samples. A total of 236 cases subject to urine cytology were enrolled in this study from January 2005 to December 2005. All cases were subjected to cystoscopy and if a malignancy was suspected, a biopsy was performed. Urine cytology slides were made using the ThinPrep(R) preparation method and the conventional Cytospin and/or direct smear method from the individual samples. The results of urine cytology were compared with the final cystoscopic or histological diagnoses. We analyzed the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of both cytology preparation methods. A total of 236 slides made using the liquid based method were satisfactory for slide quality, whereas 5 slides (2.1%) prepared by conventional methods were unsatisfactory because of air-drying, a thick smear, or a bloody or inflammatory background. The ThinPrep(R) method showed 53.1% sensitivity, 92.6% specificity, a 92.6% positive predictive value, a 94.1% negative predictive value and 85.6% accuracy, while the conventional method showed 51% sensitivity, 98.4% specificity, a 92.6% positive predictive value, a 98.4% negative predictive value and 88.6% accuracy. Although the diagnostic values were equivalent between the use of the two methods, the quality of the cytology slides and the time consumed during the microscopic examination for a diagnosis were superior for the ThinPrep(R) method than for the conventional method. In conclusion, our limited studies have shown that the use of the liquid based preparation method is beneficial to improve the quality of slides and reduce the duration for a microscopic examination, but did not show better sensitivity, accuracy and predictive values.