Clinical Impact of Natural Killer Group 2D Receptor Expression and That of Its Ligand in Ovarian Carcinomas: A Retrospective Study

Purpose@#Natural killer (NK) cells are innate immune cells with antitumor activity. NKG2D is the most important activating receptor expressed on the NK cell surface; this receptor binds to the ligands MICA/B and ULBPs to activate NK cells. The current study aimed to evaluate the expression of NKG2D by NK cells, and to the evaluate expression of its ligands in ovarian carcinomas; it also examined the clinical relevance of NK receptor/ligand expression by analyzing the relationship between expression, clinicopathological parameters, and prognosis. @*Materials and Methods@#Formalin-fixed paraffin-embedded archival ovarian high-grade serous carcinoma (HGSC, n=79) tissue samples were used for tissue microarray analysis. The expressions of NK cell markers (CD56 and NKG2D) and NKG2D ligands (MICA/B, ULBP1, ULBP3, and ULBP2/5/6) in carcinoma tissues were evaluated by immunohistochemical staining, and the association between these results and clinical prognostic parameters was analyzed statistically. @*Results@#ULBP1 was highly expressed in 51 cases (64.6%), and ULBP2/5/6 was highly expressed in 56 cases (70.9%) of HGSC. High expression of ULBP1 and ULBP2/5/6 was significantly associated with lower recurrence of HGSC, whereas high expression of ULBP3 was significantly associated with higher recurrence. Multivariate Cox regression analysis revealed that high expression of ULBP1 was associated with increased overall survival and a decreased hazard ratio (0.150, p=0.044), suggesting that it is an independent predictor of better survival. @*Conclusion@#High expression of ULBP1 predicts a better prognosis for HGSC, suggesting that ULBP1 expression could be a novel prognostic indicator in this subset of carcinomas.

Clinical Impact of Somatic Variants in Homologous RecombinationRepair-Related Genes in Ovarian High-Grade Serous Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#In this study, we investigated the frequencies of mutations in DNA damage repair genesincluding BRCA1, BRCA2, homologous recombination genes and TP53 gene in ovarian highgradeserous carcinoma, alongside those of germline and somatic BRCA mutations, withthe aim of improving the identification of patients suitable for treatment with poly(ADPribose)polymerase inhibitors. @*Materials and Methods@#Tissue samples from 77 Korean patients with ovarian high-grade serous carcinoma weresubjected to next-generation sequencing. Pathogenic alterations of 38 DNA damage repairgenes and TP53 gene and their relationships with patient survival were examined. Additionally,we analyzed BRCA germline variants in blood samples from 47 of the patients forcomparison. @*Results@#BRCA1, BRCA2, and TP53 mutations were detected in 28.6%, 5.2%, and 80.5% of the 77patients, respectively. Alterations in RAD50, ATR, MSH6, MSH2, and FANCA were also identified.At least one mutation in a DNA damage repair gene was detected in 40.3% of patients(31/77). Germline and somatic BRCA mutations were found in 20 of 47 patients (42.6%),and four patients had only somatic mutations without germline mutations (8.5%, 4/47).Patients with DNA damage repair gene alterations with or without TP53mutation, exhibitedbetter disease-free survival than those with TP53 mutation alone. @*Conclusion@#DNA damage repair genes were mutated in 40.3% of patients with high-grade serous carcinoma,with somatic BRCAmutations in the absence of germline mutation in 8.5%. Somaticvariant examination, along with germline testing of DNA damage repair genes, has potentialto detect additional candidates for PARP inhibitor treatment.

Intrahepatic Cholangiocarcinoma with Ductal Plate Malformation-like Feature Associated with Bile Duct Adenoma

No abstract available.

Characteristics of the dietary intake of Korean elderly by chewing ability using data from the Korea National Health and Nutrition Examination Survey 2007-2010 / 한국영양학회지

The purpose of this study was to examine the characteristics of the dietary intake of Korean elderly according to chewing ability using data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted during 2007-2010. Among subjects aged 65 years and over, more than half, 54.3% of elderly people, were classified as the difficulty in chewing group (DC). The DC group had lower nutrients and food intakes than those of in the no difficulty in chewing group (NDC). Findings showed that subjects in the DC group consumed fewer foods, especially fruits and vegetables. In addition, the DC group had significantly lower intakes of pan-fried food, stir-fried food, braised food, and seasoned-cooked vegetables, which could not be easily cooked or chewed. On the other hand, the number of soups and stews included in the top 30 largely consumed dishes were higher in the DC group than in the NDC group. No difference in numbers of daily meal/snack intake was observed between the two groups, however, the DC group had lower numbers of side-dishes compared to the NDC group. Fewer side-dishes per meal could be related to lower intakes of nutrients in dietary quality. Findings of this study demonstrated that dietary intake was influenced by chewing ability of elderly Korean people. Therefore, study of factors affecting dietary intake such as convenient cooking methods to decrease cooking time and skills to extend preservation and storage time of foods will necessary. In addition, development of food products and new techniques of cooking considering health status, chewing, and swallowing ability is required for the elderly, followed by establishment of standards for senior-friendly food products.

A Case of Ovarian Microinvasive Mucinous Carcinoma and Co-existent Angiosarcoma

Primary ovarian angiosarcoma is very rare with only 27 cases reported so far in the medical literature. We report here on a rare case of ovarian microinvasive mucinous carcinoma that was coexistent with angiosarcoma in a 54-year-old woman. The tumor was a 26x19x10 cm-sized multilocular cystic mass with a 4x3 cm-sized solid hematoma-like nodule in the center. Microscopically, it was composed mostly of mucinous tumor of various grades from borderline to microinvasive carcinoma. The hematoma-like area turned out to be an angiosarcoma, composed of pleomorphic cells that formed slit-like spaces, spindle cells that formed short fascicles and anastomosing vascular channels with atypical endothelial cells. All these cells were positive for CD31, CD34 and factor VIII-related antigen. The patient developed peritoneal and pleural metastases, which were angiosarcoma and mucinous carcinoma, respectively. We believe this case is only the fourth example of an ovarian collision tumor of angiosarcoma and surface epithelial tumor.

Usefulness of FDG-PET/CT as a Diagnostic Tool for Routine Post Therapy Evaluation in Endometrial Cancer / 핵의학분자영상

PURPOSE: The aim of this study was to evaluate the usefulness of FDG-PET/CT as follow up imaging tool in patients with endometrial cancer after therapy. Material and Methods: One hundred one patients with endometrial cancer who underwent FDG PET/CT after the treatment of this disease were included in this study population (25-79 yr old, Mean age 50.6 yr old) and all these patients also performed various laboratory and imaging studies such as serum tumor marker, CT or MRI. The lesions having increased focal FDG uptake were classified into benign, equivocal, and malignant one according to their pattern and activity. Tumor recurrence was confirmed by histopathological results and other clinical and imaging data. RESULTS: Among the 19 patients with 30 malignant or equivocal hot uptakes, 11 of 14 patients supposed to be malignant finding in PET/CT were proved to be tumor recurrence, while one of 5 patients with equivocal lesions were recurred malignancy. Two false negative cases were turned out to be peritoneal carcinomatosis. Estimated sensitivity, specificity and accuracy of PET/CT for diagnosis of recurrence in endometrial carcinoma after treatment were 86 %, 92 % and 91%, respectively. Positive and negative predictive values in the same issue were 63% and 98%, respectively. CONCLUSION: FDG-PET/CT is useful for regular work up of endometrial carcinoma after the treatment because of its high negative predictive value as well as high sensitivity and specificity.

The Loss of E-cadherin is Associated with the Epigenetic Alteration of CDH1 in Breast Cancer and it is also Associated with an Abnormal beta-catenin Expression in Lobular Carcinoma

BACKGROUND: APC and E-cadherin are the key molecules in the Wnt/beta-catenin pathway. We attempted to define the epigenetic alteration of APC and CDH1 (the E-cadherin gene) and the expression of Wnt-related molecules in human mammary carcinomas. METHODS: Sixty-four mammary carcinomas, including 52 invasive ductal carcinomas (IDCs) and 12 invasive lobular carcinomas (ILCs), were evaluated using methylation-specific PCR and immunohistochemistry. We performed immunohistochemistry for E-cadherin, beta-catenin, APC, Wnt1, cyclin D1, ER, PR and C-erb B2. RESULTS: Hypermethylation of APC and CDH1 was observed in 38 (59%) and 28 (44%) cases, respectively. CDH1 hypermethylation in ILCs was increased compared to that in IDCs (p=0.002) and it was associated with the loss of E-cadherin (p=0.02) and beta-catenin (p=0.042). APC methylation was positively correlated with the ER expression (p=0.021). Abnormal cytoplasmic localization of beta-catenin was found in 10 cases and any expression was not detected in six cases. In ILCs, the E-cadherin or beta-catenin expression was markedly decreased compared to that in IDCs (p<0.001 in both). CONCLUSIONS: Methylation of APC or CDH1 was relatively frequent in mammary carcinomas. The loss of E-cadherin in mammary carcinoma was associated with CDH1 methylation, and abnormal beta-catenin expression was related to the loss of E-cadherin in ILC.

A Multiinstitutional Consensus Study on the Pathologic Diagnosis of Endometrial Hyperplasia and Carcinoma

BACKGROUND: The purpose of this study was to examine the reproducibility of both the diagnosis of endometrial hyperplasia (EH) or adenocarcinoma, and the histologic grading (HG) of endometrioid adenocarcinoma (EC). METHODS: Ninety-three cases of EH or adenocarcinomas were reviewed independently by 21 pathologists of the Gynecologic Pathology Study Group. A consensus diagnosis was defined as agreement among more than two thirds of the 21 pathologists. RESULTS: There was no agreement on the diagnosis in 13 cases (14.0%). According to the consensus review, six of the 11 EH cases (54.5%) were diagnosed as EH, 48 of the 57 EC cases (84.2%) were EC, and 5 of the 6 serous carcinomas (SC) (83.3%) were SC. There was no consensus for the 6 atypical EH (AEH) cases. On the HG of EC, there was no agreement in 2 cases (3.5%). According to the consensus review, 30 of the 33 G1 cases (90.9%) were G1, 11 of the 18 G2 cases (61.1%) were G2, and 4 of the 4 G3 cases (100.0%) were G3. CONCLUSIONS: The consensus study showed high agreement for both EC and SC, but there was no consensus for AEH. The reproducibility for the HG of G2 was poor. We suggest that simplification of the classification of EH and a two-tiered grading system for EC will be necessary.

A Comparison of Conventional Cytology and ThinPrep Cytology of Bronchial Washing Fluid in the Diagnosis of Lung Cancer / 결핵및호흡기질환

Background: A ThinPrep(R) Processor was developed to overcome the limitations of conventional cytology and is widely used to diagnose various cancers. This study compared the diagnostic efficacy of conventional cytology for lung cancer with that of the ThinPrep(R) cytology using the bronchial washing fluid. Methods: The bronchial washing fluid of 790 patients from Jan. 2002 to Dec. 2006, who were suspected of gaving a lung malignancy, was evaluated. Both ThinPrep(R) and conventional cytology were performed for all specimens. Result: Four hundred forty-six men and 344 women were enrolled in this study, and 197 of them were diagnosed with cancer from either a bronchoscopic biopsy or a percutaneous needle aspiration biopsy. ThinPrep(R) cytology showed a sensitivity, specificity, positive predictive value, negative predictive value and false negative error rate of 71.1%, 98.0%, 92.1%, 91.1%, 8.9%, respectively. The conventional cytology showed sensitivity, specificity, positive predictive value, nagative predictive value and false negative error rate of 57.9%, 98.0%, 90.5%, 87.5%, 12.5%, respectively. For central lesions, the sensitivity of conventional cytology and ThinPrep(R) were 70.1% and 82.8%, respectively. Conclusion: ThinPrep(R) cytology showed a higher sensitivity and lower false negative error rate than conventional cytology. This result was unaffected by the histological classification of lung cancer. Therefore, ThinPrep(R) cytology appears to be a useful method for increasing the detection rate of lung cancer in bronchial washing cytology test.

A Case of Hemophagocytic Syndrome with Terminal Ileal Ulcerations / 대한소화기학회지

Reactive hemophagocytic syndrome or hemophagocytic lymphohistiocytosis, is characterized by the proliferation of benign histiocytes showing phagocytosis of blood cells in hematopoietic organs including bone marrow, spleen, or lymph nodes, accompanied by fever, hepatosplenomegaly, hepatic dysfunction, pancytopenia, and hypertriglyceridemia. The pathogenesis of reactive hemophagocytic syndrome is unknown. It is often associated with infection, malignant neoplasm, autoimmune disease, drugs and various immunodeficiencies. The prognosis of this syndrome is poor and the causes of death are hemorrhage, infection, or multiorgan failure. We experienced a case of hemophagocytic syndrome with terminal ileal ulcers, not associated with other causes. Thus, we report this case with a review of literatures.

Application of Autologous Tumor Vaccine as an Adjuvant Immunotherapy in the Treatment of Metastatic Renal Cell Carcinoma / 대한비뇨기과학회지

About 50% of renal cell carcinoma patients initially present with a regional or distant metastatic disease. Attempts to treat metastatic renal cell carcinomas have been directed at cytokine-based immunotherapy. Response rates of interleukin-2-based immunotherapy of 5 to 29% have been reported in this disease. Immunization as a mechanism to recruit host antitumor responses is increasingly being described as a potentially effective and less toxic approach for the treatment of metastatic and high-risk primary cancers. An autologous renal cell cancer vaccine has been applied at our institution for the prevention of recurrence or metastasis in locally advanced cases for more than one year. Herein, two metastatic renal cell carcinoma cases, which failed to show a response to initial immunotherapy or chemoradiotherapy, which were successfully treated with IL-2 (Aldesleukin) and interferon-alpha as autologous cancer vaccine adjuvants is reported.

Ureteral Substitution Using Appendix in a Ureteral Defect Caused by a Retroperitoneal Paraganglioma / 대한비뇨기과학회지

Exraadrenal paragangliomas are rare tumors of a neural crest origin. Their preoperative diagnosis can be suspected from the clinical history and biochemical examination of the catecholamines or their metabolic by-products. Surgery is the mainstay of therapy, but surgical removal makes an additional problem for the repair of the ureteral defect if a paraganglioma is located near the ureter or if it encloses the ureter. The ureteral repair often poses a therapeutic dilemma, and especially when the ureteral defect is too extensive to be repaired with traditional methods. We report here on a case of successful replacement with using appendix for the repair of a long ureteral defect that was caused by a retroperitoneal paraganglioma.

Characterization of the Differentially Expressed Genes in Human Breast Cancer using Subtractive Hybridization / 한국유방암학회지

PURPOSE: Although breast cancer the most common cancer for women remains a significant health problem, it has not been systematically studied until now. In an attempt to identify novel genes implicated in breast cancer development, we performed a suppression subtraction hybridization (SSH) with human breast cancer tissues, as well as with cloned genes, that are expressed more than in normal tissue. METHODS: After the identification of a novel gene, RT-PCR was performed to determine its mRNA expression in human breast cancers. In order to learn more about the expression profile of this gene, PCR was performed using various commercially available normal or carcinoma cell lines. The novel gene was found to be strongly expressed in breast cancer tissues and other carcinoma cell lines. To determine whether this novel gene was associated with cell cycle regulation, normal WI-38 fibroblast cells were stimulated with media containing 0.1% FBS for 48hours. RESULT: From the experimental results of the SSH, a novel clone, "Clone 135" which was strongly expressed in tumor compared to matched normal tissue, has been found. The novel clone was identified as being expressed in several tumor tissues and carcinoma cell lines. The time-course expression of this novel gene in the WI-38 (8PDL) normal lung cell line indicated a significant increase for G1-phase arrest. CONCLUSION: We have used a suppression subtractive hybridization (SSH) to generate a profile of genes overexpressed in human breast cancer. We have screened novel genes, of which "Clone 135" scored as a candidate oncogene that was overexpressed in tumor compared to matched normal tissue.

Characterization of the Differentially Expressed Genes in Human Breast Cancer using Subtractive Hybridization / 한국유방암학회지

PURPOSE: Although breast cancer the most common cancer for women remains a significant health problem, it has not been systematically studied until now. In an attempt to identify novel genes implicated in breast cancer development, we performed a suppression subtraction hybridization (SSH) with human breast cancer tissues, as well as with cloned genes, that are expressed more than in normal tissue. METHODS: After the identification of a novel gene, RT-PCR was performed to determine its mRNA expression in human breast cancers. In order to learn more about the expression profile of this gene, PCR was performed using various commercially available normal or carcinoma cell lines. The novel gene was found to be strongly expressed in breast cancer tissues and other carcinoma cell lines. To determine whether this novel gene was associated with cell cycle regulation, normal WI-38 fibroblast cells were stimulated with media containing 0.1% FBS for 48hours. RESULT: From the experimental results of the SSH, a novel clone, "Clone 135" which was strongly expressed in tumor compared to matched normal tissue, has been found. The novel clone was identified as being expressed in several tumor tissues and carcinoma cell lines. The time-course expression of this novel gene in the WI-38 (8PDL) normal lung cell line indicated a significant increase for G1-phase arrest. CONCLUSION: We have used a suppression subtractive hybridization (SSH) to generate a profile of genes overexpressed in human breast cancer. We have screened novel genes, of which "Clone 135" scored as a candidate oncogene that was overexpressed in tumor compared to matched normal tissue.

Expression of Chemokine Receptors in Ovarian Cancer Tissue / 대한산부인과학회잡지

OBJECTIVE: We investigated the expression of chemokine receptors in human ovarian cancer to understand the role of chemokines in ovarian cancer development and metastasis. METHODS: Twenty-two cases of epithelial ovarian cancer were studied for expression of 13 chemokine receptors such as CXCR1-CXCR5 and CCR1-CCR8 by using semi- quantitative RT-PCR and immunohistochemistry. Moreover, we studied the relationship between the chemokine receptors expression and lymph nodes metastasis of ovarian cancers. RESULTS: As compared with normal ovarian tissues, ovarian cancer tissues showed higher mean expression levels of CCR1,3,4,5,7,8 and CXCR1,3,4. Of chemokine receptors, CCR7 revealed the significantly higher levels of expression in ovarian cancer tissues relative to normal tissues. In the cases of retroperitoneal lymph nodes metastasis, increased expression of CCR2,4 and CXCR 1,3,4 was observed although there was no statistical significance. CONCLUSION: These results suggest that there is a complex chemokine/chemokine receptor network in pathogenesis and the way of lymph node metastasis of ovarian cancer rather than a specific chemokine or chemokine receptor.