BACKGROUND Alterations in the phosphatase and tensin homolog (PTEN) are correlated with tumor progression.
Downregulation of PTEN is related to drug resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the prognostic significance of PTEN in patients with NSCLC and its correlation with EGFR. METHODS Two hundred eighty eight surgically resected NSCLC samples, including 168 adenocarcinomas (ADCs), 99 squamous cell carcinomas (SCCs) and 21 other NSCLCs were analyzed for the PTEN. The results were correlated with other clinicopathological variables including EGFR amplification and mutation. RESULTS Loss of PTEN was detected in 42.4% of NSCLCs, specifically 28.6% of ADCs, 66.7% of SCCs, and 38.1% of others. Loss of PTEN was significantly associated with SCC, smoking, male gender, and higher stage. In a multivariate analysis, loss of PTEN was significantly associated with short progression-free survival (p=0.037). No association between PTEN and EGFR was observed. CONCLUSIONS These results suggest that loss of PTEN results in shorter progression-free survival in patients with NSCLC, and loss of PTEN is more associated with SCC, smoking, male gender, and higher T stage by the 7th tumor, node and metastasis staging system but not EGFR status.
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BACKGROUND The weight, shape and consistency of the heart, and the thickness of the ventricular wall are used as parameters for evaluating postmortem heart and diagnosing cardiomyopathy at autopsy. METHODS The weight and volume of the ventricles and the thickness of the left ventricular wall of 58 hearts were measured and analyzed. RESULTS In the group of dilated hearts, the ventricular weight, ventricular volume, ventricular volume/ventricular weight, and left ventricular volume/right ventricular volume increased, whereas ventricular wall thickness decreased. In the group of hypertrophied hearts, the ventricular weight, ventricular volume, and thickness of the ventricular wall increased but ventricular volume/ventricular weight and left ventricular volume/right ventricular volume did not change significantly. In the group of undetermined hearts, it was later found that four of the cases should have been included in the dilated heart group and another two cases in the hypertrophied heart group. CONCLUSIONS In addition to conventional methods, the measuring ventricular volume is useful for evaluating a postmortem heart and may suggest postmortem differential diagnoses of dilated or hypertrophied forms of secondary cardiomyopathies.
BACKGROUND Human papillomavirus (HPV) plays an important role in the development of cervical carcinoma. Although there is a general agreement that high levels of HPV are related to cervical cancer, the prevalence and distribution of HPV genotypes seems to vary by geographical region. This study was designed to investigate the prevalence of HPV genotypes in Gangwon Province, Korea. METHODS In total, 342 samples were examined by Pap smear and HPV-ID(R) reverse blot hybridization assay (REBA) (M&D, Wonju, Korea). RESULTS Overall HPV positivity was 80.9% and 64.4% in women with abnormal and normal cytology by REBA, respectively. The five most common HPV types were: HPV 16, 53, 58, 56, and 33 in samples with abnormal cytology, and HPV 16, 53, 58, 70, and 18 in samples with normal cytology. CONCLUSIONS The REBA can provide useful data regarding prevalence of HPV genotypes. Gangwon Province showed high prevalence of HPV infection in women. The most common HPV type in Gangwon Province was HPV16, and HPV 53, 58, 56, 70 were frequently present.
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BACKGROUND MicroRNA (miRNA) is a class of noncoding protein RNA as a promising biomarker for various diseases. In this study, the expression of let-7b, miR-30c, and miR-200c was studied in breast cancer tissues to evaluate the potential relationship with known clinicopathological parameters. METHODS Quantitative real-time polymerase chain reaction was performed to determine the expression level of three miRNAs in 37 pairs of noncancerous normal and cancer tissues and an additional 38 cancer tissues from patients with invasive ductal carcinoma. RESULTS miR-200c expression was higher in cancer tissues compared to noncancerous normal tissues, and its ratio was correlated with patient age at surgery, type of surgery, and Ki-67 expression. The expression level of let-7b in cancer tissues was inversely correlated with lymph node metastasis, histological grade, and Ki-67 expression but positively correlated with estrogen and progesterone receptor expression. miR-200c expression level was positively correlated with Her-2 expression. The miR-30c expression level in breast cancer was not correlated with any parameters. CONCLUSIONS miR-200c and let-7b could be used as biomarkers in patients with breast cancer, but its pathological mechanism should be determined.
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BACKGROUND Malignant tumor cells may evoke the innate and adaptive immune systems. Various immune cells are involved in this immune reaction, and tumor infiltrating lymphocytes, macrophages, natural killer (NK) cells are associated with patient prognosis for solid tumors. METHODS Seventy-eight patients who were diagnosed with diffuse large B cell lymphoma (DLBCL) between 2001 and 2009 were selected. CD57+ NK cells, CD68+ tumor associated macrophages (TAMs), and CD4+ and CD8+ T cells were evaluated in tissue sections using immunohistochemical staining and compared with clinical parameters including age, gender, performance status, clinical stage, serum lactic dehydrogenase level, number of extranodal sites, international prognostic index score, chemotherapy response, and survival. RESULTS Patients with high numbers of CD57+ NK cells had a significantly higher overall survival rate than patients with low numbers of CD57+ NK cells. However, no significant difference was observed between the number of CD57+ NK cells and other prognostic parameters. The number of CD68+ TAMs and CD4+ or CD8+ T cells was not significantly correlated with prognostic factors in patients with DLBCL. CONCLUSIONS An evaluation of tumor infiltrating CD57+ NK cells is recommended as a prognostic indicator in patients with DLBCL.
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BACKGROUND Recent reports have indicated that renal cell carcinoma (RCC) with rhabdoid features follows an aggressive clinical course. We investigated the prognostic significance and nature of the rhabdoid component. METHODS We retrospectively analyzed the incidence and clinicopathologic characteristics of RCC with rhabdoid features in 174 radical nephrectomy cases. The specimens were examined histologically and immunohistochemically. RESULTS Twelve of the 174 RCC cases (6.9%) showed rhabdoid features. Histologically, all the tumors with rhabdoid features were of the clear cell type. The presence of rhabdoid features was significantly associated with higher Fuhrman's nuclear grade and higher pathologic tumor stage at presentation. Among the 12 patients who showed the rhabdoid component, nine (75%) developed metastasis and seven (58.3%) died of disease-related causes. The presence of rhabdoid features was independently associated with metastasis and disease-related mortality. The rhabdoid cells were positive for vimentin; variably positive for pan-cytokeratin, epithelial membrane antigen, and CD10; and negative for cytokeratin 7, smooth muscle actin, desmin, E-cadherin, and c-Kit. No case showed loss of integrase interactor-1; one was p53 positive, and five were insulin-like growth factor mRNA binding protein 3 positive. The Ki-67 labeling index was 1-25% (mean, 5.5%). CONCLUSIONS The rhabdoid component is an independent prognostic factor for metastasis of RCC; therefore, identification of this component is critical.
BACKGROUND Recent studies have demonstrated that insulin-like growth factor II mRNA-binding protein 3 (IMP3) is expressed in malignant tumors of various organs but not in normal tissue. We investigated IMP3 expression in various benign lesions, premalignant lesions and carcinomas of the stomach. METHODS IMP3 immunohistochemical staining was performed on 24 benign gastric lesions, 24 gastric adenomas, and 322 gastric carcinomas. RESULTS IMP3 was not expressed in benign gastric lesions including adenomas with low-grade dysplasia, but was expressed in 17% of adenomas with high-grade dysplasia, and in 44% of carcinomas. As the carcinomas were in the advanced stage, they expressed IMP3 more frequently and strongly.
Patients with IMP3-positive tumors had poorer survival than those with negative tumors. CONCLUSIONS IMP3 expression in gastric carcinoma may be related to tumor invasion and metastasis, and is an independent risk factor for poor prognosis.
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BACKGROUND One of the histone acetyltransferases (HATs) family of proteins, human MOF (hMOF, MYST1), is involved in histone H4 acetylation, particularly at lysine 16 (H4K16Ac), an epigenetic mark of active genes. Dysregulation of the epigenetic mark influences cellular biology and possibly leads to oncogenesis. We examined the involvement of hMOF and H4K16Ac in primary non-small cell lung cancer (NSCLC). METHODS Reverse transcription polymerase chain reaction using fresh-frozen lung cancer tissues and lung cancer cell lines and immunohistochemistry for hMOF and H4K16Ac via tissue microarray of 551 formalin-fixed paraffin-embedded NSCLC tissue blocks were conducted. RESULTS hMOF mRNA was frequently overexpressed in lung cancer tissues, compared with normal lung tissues (10/20, 50%). NSCLC tissues were positive for hMOF in 37.6% (184/489) and H4K16Ac in 24.7% (122/493) of cases. hMOF protein expression was tightly correlated with the H4K16Ac level in tumors (p<0.001). Knockdown of hMOF mRNA with siRNA led to a significant inhibition of growth in the Calu-6 cell line. CONCLUSIONS hMOF was frequently expressed in NSCLC and was correlated with H4K16Ac. To our knowledge, this is the first study that has focused on the expression status of HATs and hMOF in NSCLC. Our results clearly suggest a potential oncogenic role of the gene and support its utility as a potential therapeutic target.
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Stabilization of MOF (KAT8) by USP10 promotes esophageal squamous cell carcinoma proliferation and metastasis through epigenetic activation of ANXA2/Wnt signaling Peichao Li, Lingxiao Yang, Sun Young Park, Fanrong Liu, Alex H. Li, Yilin Zhu, Huacong Sui, Fengyuan Gao, Lingbing Li, Lan Ye, Yongxin Zou, Zhongxian Tian, Yunpeng Zhao, Max Costa, Hong Sun, Xiaogang Zhao Oncogene.2024; 43(12): 899. CrossRef
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Histone Acetyltransferase MOF Orchestrates Outcomes at the Crossroad of Oncogenesis, DNA Damage Response, Proliferation, and Stem Cell Development Mayank Singh, Albino Bacolla, Shilpi Chaudhary, Clayton R. Hunt, Shruti Pandita, Ravi Chauhan, Ashna Gupta, John A. Tainer, Tej K. Pandita Molecular and Cellular Biology.2020;[Epub] CrossRef
The Functional Analysis of Histone Acetyltransferase MOF in Tumorigenesis Jiaming Su, Fei Wang, Yong Cai, Jingji Jin International Journal of Molecular Sciences.2016; 17(1): 99. CrossRef
Expression of hMOF, but not HDAC4, is responsible for the global histone H4K16 acetylation in gastric carcinoma LIN ZHU, JIAXING YANG, LINHONG ZHAO, XUE YU, LINGYAO WANG, FEI WANG, YONG CAI, JINGJI JIN International Journal of Oncology.2015; 46(6): 2535. CrossRef
Arsenic Trioxide Reduces Global Histone H4 Acetylation at Lysine 16 through Direct Binding to Histone Acetyltransferase hMOF in Human Cells Da Liu, Donglu Wu, Linhong Zhao, Yang Yang, Jian Ding, Liguo Dong, Lianghai Hu, Fei Wang, Xiaoming Zhao, Yong Cai, Jingji Jin, Tim Thomas PLOS ONE.2015; 10(10): e0141014. CrossRef
The histone acetyltransferase hMOF suppresses hepatocellular carcinoma growth Jin Zhang, Hui Liu, Hao Pan, Yuan Yang, Gang Huang, Yun Yang, Wei-Ping Zhou, Ze-Ya Pan Biochemical and Biophysical Research Communications.2014; 452(3): 575. CrossRef
Regulation and function of histone acetyltransferase MOF Yang Yang, Xiaofei Han, Jingyun Guan, Xiangzhi Li Frontiers of Medicine.2014; 8(1): 79. CrossRef
The histone acetylranseferase hMOF acetylates Nrf2 and regulates anti‐drug responses in human non‐small cell lung cancer Zhiwei Chen, Xiangyun Ye, Naiwang Tang, Shengping Shen, Ziming Li, Xiaomin Niu, Shun Lu, Ling Xu British Journal of Pharmacology.2014; 171(13): 3196. CrossRef
Correlation of low expression of hMOF with clinicopathological features of colorectal carcinoma, gastric cancer and renal cell carcinoma LINGLING CAO, LIN ZHU, JIAXING YANG, JIAMING SU, JINSONG NI, YUJUN DU, DA LIU, YANFANG WANG, FEI WANG, JINGJI JIN, YONG CAI International Journal of Oncology.2014; 44(4): 1207. CrossRef
Coactivator MYST1 Regulates Nuclear Factor-κB and Androgen Receptor Functions During Proliferation of Prostate Cancer Cells Anbalagan Jaganathan, Pratima Chaurasia, Guang-Qian Xiao, Marc Philizaire, Xiang Lv, Shen Yao, Kerry L. Burnstein, De-Pei Liu, Alice C. Levine, Shiraz Mujtaba Molecular Endocrinology.2014; 28(6): 872. CrossRef
A potential diagnostic marker for ovarian cancer: Involvement of the histone acetyltransferase, human males absent on the first NING LIU, RUI ZHANG, XIAOMING ZHAO, JIAMING SU, XIAOLEI BIAN, JINSONG NI, YING YUE, YONG CAI, JINGJI JIN Oncology Letters.2013; 6(2): 393. CrossRef
Epigenetic change in kidney tumor: downregulation of histone acetyltransferase MYST1 in human renal cell carcinoma Yong Wang, Rui Zhang, Donglu Wu, Zhihua Lu, Wentao Sun, Yong Cai, Chunxi Wang, Jingji Jin Journal of Experimental & Clinical Cancer Research.2013;[Epub] CrossRef
BACKGROUND The expression of the inhibitor of apoptosis proteins (IAPs) family has not been fully investigated in colorectal carcinomas. This study investigated IAP expression in colorectal carcinomas and assessed their prognostic significance. METHODS Livin, XIAP, and SMAC/DIABLO expression was assessed by immunohistochemistry in 159 colorectal carcinomas. Correlations between protein expression and clinicopathological features were evaluated. The survival data analysis was estimated according to the Kaplan-Meier method. RESULTS Increased expression of IAPs in cancer tissues compared to surrounding nonneoplastic counterparts was observed in 67 cases (42.1%) for Livin, 50 cases (31.4%) for XIAP, and 68 cases (42.8%) for SMAC. A significant correlation was found between Livin expression and tumor differentiation, and SMAC expression and tumor location. The recurrence-free and overall survival of patients with low Livin expression were inferior to those of patients with high Livin expression (p=0.054 and 0.095, respectively).
High XIAP expression was significantly associated with shorter progression-free survival (p= 0.041). CONCLUSIONS Our study demonstrated that altered expression of IAP family members, including Livin, XIAP, and SMAC, is frequent in colorectal carcinoma. This result suggests that high Livin expression and low XIAP expression may be a favorable prognostic implication related to patient survival.
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BACKGROUND Nodal marginal zone lymphoma (NMZL) is a rare B-cell neoplasm consisting of heterogeneous cellular components and residual B-cell follicles. Because of such histological features, it is difficult to diagnose NMZL by fine needle aspiration (FNA) cytology. We reviewed FNA cytology of NMZL to identify a cytological clue to avoid misdiagnosing NMZL. METHODS Histological, cytological, and clinical findings of seven cases of NMZL were reviewed. RESULTS Most cases showed nodular aggregates of lymphohistiocytes derived from the germinal center irrespective of histological pattern. The cellular components were heterogeneous and composed of mature small lymphocytes, intermediate and large lymphocytes, immunoblasts, tingible body macrophages, and follicular dendritic cells. Intermediate-sized neoplastic cells with a pale nucleus were observed but difficult to identify because of admixed non-neoplastic cells, which outnumbered neoplastic cells. Except for one case with a high proportion of intermediate-sized cells, the other six cases were initially diagnosed as reactive hyperplasia. A flow cytometric analysis was performed in two cases and failed to demonstrate a monoclonal B-cell population. CONCLUSIONS The FNA showing a reactive hyperplasia-like smear pattern should be carefully observed by experienced cytopathologists to identify intermediate-sized neoplastic cells. Clinical information including the size of the lymph nodes is important to avoid a misdiagnosis.
Carcinosarcoma of the salivary glands is a rare malignant tumor showing both malignant epithelial and mesenchymal components. Herein, we present a carcinosarcoma of the parotid gland in a 67-year-old man consisting of osteosarcoma and adenocarcinoma components with fine needle aspiration cytological findings. The tumor was composed predominantly of osteosarcoma and small areas of adenocarcinomatous components and a hyalinized nodule reminiscent of pleomorphic adenoma. The tumor showed infiltrative growth features with perineural, lymphatic, and vascular invasion. Despite postoperative adjuvant radiation therapy, multiple metastatic lesions occurred in the both lungs 5 months after surgery. As salivary gland carcinosarcoma has been known to demonstrate highly aggressive behavior, an accurate pathological diagnosis is prerequisite for appropriate treatment.
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We report an extraordinary case of diffuse large B-cell lymphoma arising in a cystic necrotic mass in a 35-year-old man who presented with a soft tissue mass at the site of previous surgery. A benign mass was surgically removed 17 years ago, after which a cystic lesion gradually developed at the same site. The resected mass appeared as a thick-walled cyst filled with brown necrotic and hemorrhagic material. On microscopic examination, the cyst wall was primarily necrotic tissue with some aggregates of large atypical lymphoid cells. These atypical cells were diffusely positive for CD20 and showed a high proliferation index, Epstein-Barr virus positivity, and clonal rearrangement of the immunoglobulin gene. His present condition was diagnosed as Epstein-Barr virus-associated diffuse large B-cell lymphoma arising from chronic inflammation. It is important to be aware of the clinical manifestations and histological features of this rare disease in light of diagnosis and treatment.
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Neuroblastoma is a malignant tumor of primordial neural crest origin. It usually develops along the sympathetic nervous system, such as the adrenal glands or paramedian sympathetic chain and metastasizes to the liver most frequently. However, a primary hepatic neuroblastoma has not been reported yet. Here, we report a case of 29-year-old woman who presented with a solitary hepatic mass. Grossly, the mass was large, creamy, rubbery firm, and showed focal hemorrhage and central cavitation. Microscopically, the tumor cells were arranged in small nests of spindle to ovoid cells with abundant neuropil. The neuroblastic nature of the tumor was confirmed by immunohistochemistry and electron microscopy. No extrahepatic mass was found, despite a thorough systemic survey such as chest and abdominopelvic computed tomography (CT) scans and a whole body positron emission tomography-CT study. To the best of our knowledge, this is the first report of a bona fide primary hepatic neuroblastoma.
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A hyalinizing trabecular adenoma (HTA) is a rare benign thyroid tumor of follicular epithelial cell origin with a trabecular-alveolar growth pattern and marked intratrabecular hyalinization. The cytological and histological features of HTA are very similar to those of papillary and medullary carcinomas of the thyroid.
Therefore, an accurate diagnosis of HTA is important to avoid unnecessary and potentially harmful management of patients. However, the results of BRAF gene mutation analysis shown by many studies are distinctly different between HTAs and papillary thyroid carcinomas. Herein, we describe a rare case of HTA of the thyroid in a 49-year-old female and consider its characteristic cytological features and BRAF gene mutation analysis results with a brief review of the literature.
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Liver penetration is one of the most serious complications of peptic ulcer diseases but is rarely encountered. A 57-year-old man was admitted to our hospital for further evaluation of a gastric malignancy. One month before admission, he was diagnosed with an adenocarcinoma by endoscopic biopsy at other hospital. A subtotal gastrectomy was performed to confirm malignancy and relieve the epigastric pain. Histologically, single glands were located between the ulcer base and attached liver tissue and stained positively for cytokeratin 19. The pathologic diagnosis was a gastric ulcer and bile ductular proliferation in the liver and gastric wall. Here, this report is the first Korean case of liver penetration of a gastric ulcer.