PURPOSE: Loss of AT-rich DNA-interacting domain 1A (ARID1A) has been identified as a driving mutation of ovarian clear cell carcinoma (O-CCC), a triple-negative ovarian cancer that is intermediary between serous and endometrioid subtypes, in regards to molecular and clinical behaviors. However, about half of O-CCCs still express BAF250a, the protein encoded by ARID1A. Herein, we aimed to identify signatures of ARID1A-positive O-CCC in comparison with its ARID1A-negative counterpart. MATERIALS AND METHODS: Seventy cases of O-CCC were included in this study. Histologic grades and patterns of primary tumor, molecular marker immunohistochemistry profiles, and clinical outcomes were analyzed. RESULTS: Forty-eight (69%) O-CCCs did not express BAF250a, which were designated as "ARID1A-negative." The other 22 (31%) O-CCCs were designated as "ARID1A-positive." ARID1A-positive tumors were more likely to be histologically of high grades (41% vs. 10%, p=0.003), ERβ-positive (45% vs. 17%, p=0.011), and less likely to be HNF1β-positive (77% vs. 96%, p=0.016) and E-cadherin-positive (59% vs. 83%, p=0.028) than ARID1A-negative tumors. Patient age, parity, tumor stage were not significantly different in between the two groups. Cancer-specific survival was not significantly different either. CONCLUSION: We classified O-CCCs according to ARID1A expression status. ARID1A-positive O-CCCs exhibited distinct immunohistochemical features from ARID1A-negative tumors, suggesting a different underlying molecular event during carcinogenesis.
Adenocarcinoma, Clear Cell/*metabolism/mortality/pathology ; Adult ; Aged ; Biomarkers, Tumor/metabolism ; Cadherins/metabolism ; Estrogen Receptor beta/metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Mutation ; Neoplasm Proteins/*metabolism ; Nuclear Proteins/*metabolism ; Ovarian Neoplasms/*metabolism/mortality/pathology ; Transcription Factors/*metabolism

Lung cancer rarely occurs in young patients. Recent studies have demonstrated that epidemiologic data are closely correlated to some molecular characteristics. We investigated the clinicopathologic characteristics of lung adenocarcinoma in young patients and evaluated immunohistochemically detected epidermal growth factor receptor (EGFR) mutation status and anaplastic lymphoma kinase (ALK) positivity. Among lung adenocarcinoma patients, 31 cases were of the < or = 40 yr-old group and 261 cases of > 50 yr-old group. Young patients were more likely to be females (67.7% vs 40.2%), and nonsmokers (58.1% vs 45.2%) and more often had high TNM stage (stage IV was 80.6% vs 52.1%) and had a high rate of distant metastasis (51.6% vs 28.0%) compared with older patients. The signet ring cell feature was more common (25.8% vs 11.5%) and lepidic growth pattern was rarely present (3.2% vs 16.5%) in the adenocarcinoma of young patients. There was no significant survival difference between the two age groups. The rate of EGFR mutation status and ALK positivity did not show a statistical difference between two groups. In conclusion, lung adenocarcinoma of young patients demonstrates distinct pathologic features with frequent presence of a signet ring cell feature and rare occurrence of lepidic growth pattern. Further investigation for other genetic abnormalities would be needed.
Adenocarcinoma/metabolism/mortality/*pathology ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung Neoplasms/metabolism/mortality/*pathology ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptor, Epidermal Growth Factor/metabolism ; Smoking

The most appropriate time to introduce androgen deprivation therapy for prostate cancer remains controversial. Our aim was to evaluate the effects of early versus delayed surgical castration on prostate cancer progression and survival in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. TRAMP mice were randomly divided into three groups: the early castration group (on which castration was performed at the age of 4 weeks), the delayed castration group (on which castration was performed when abdominal tumours could be palpated), and the sham-castrated group. Mice were monitored daily throughout their lives until cancer-related death or the development of an obviously moribund appearance, at which time the individual mouse was killed. Androgen receptor expression in prostate tumours was also evaluated. The results shows that the average lifespan in early castration, delayed castration and sham-castrated groups were 54.1 weeks, 59.9 weeks and 39.1 weeks, respectively. Both early castration and delayed castration conferred a statistically significant survival advantage when compared with the sham-castrated group (P<0.001). However, the difference in lifespan between the early castration group and the delayed castration group was not statistically significant (P=0.85). The increase in lifespan in the TRAMP mice that received either early or delayed castration correlated with lower G/B value (genitourinary tract weight/body weight) at death than the sham-castrated mice. In conclusion, early and delayed castrations in TRAMP mice prolonged survival to a similar extent. This finding may provide a guide for clinical practice in prostate cancer therapy.
Adenocarcinoma ; mortality ; pathology ; surgery ; Animals ; Body Weight ; Disease Models, Animal ; Kaplan-Meier Estimate ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Orchiectomy ; Organ Size ; Prostate ; metabolism ; pathology ; surgery ; Prostatic Neoplasms ; mortality ; pathology ; surgery ; Receptors, Androgen ; metabolism ; Time Factors ; Transgenes ; genetics

Small pancreatic cancers (longest diameter < or =2 cm) have been regarded as preliminary to early pancreatic cancer, which was thought to be highly curable. During our experience since 1989, we evaluated 542 cases of pancreatic cancer. Among them we found 74 cases of tumors < or =2 cm in diameter, small pancreatic cancer (TS1 pancreatic cancer). Well-differentiated adenocarcinomas (18.9%) and absence of symptoms (8.1%) were more frequent in patients with TS1 than in those with larger pancreatic tumors. Only 16 of the 74 patients (21.6%) with small pancreatic cancers had T1 tumors. According to the International Union Against Cancer (UICC) staging, only 11 patients (14.9%) were stage IA: their 5-yr survival rate was 23.3% and their median survival was 30.0 months. Among these 11 patients, 3 had tumors <1 cm; their median survival time was 30.0 months and their 5-yr survival rate was 50.0%. These findings may indicate that 'small' pancreatic cancer is not equivalent to 'early' pancreatic cancer.
Adenocarcinoma/pathology ; Adenocarcinoma, Mucinous/pathology ; Adenocarcinoma, Papillary/pathology ; Adult ; Aged ; CA-19-9 Antigen/metabolism ; Carcinoembryonic Antigen/metabolism ; Carcinoma/pathology ; Carcinoma, Adenosquamous/pathology ; Carcinoma, Pancreatic Ductal/pathology ; Female ; Humans ; Korea/epidemiology ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatic Neoplasms/immunology/mortality/*pathology ; Prognosis ; Survival Rate ; Tumor Burden

Hypoxia-inducible factor-1 alpha (HIF-1α) plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1α in lung cancer. The relationship between HIF-1α and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. PubMed and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF-1α expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1α in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer (NSCLC) patients had higher HIF-1α expression than small cell lung cancer (SCLC) patients. Moreover, lymph node metastasized tissues had higher HIF-1α expression than non-lymph node metastasized tissues. A high level HIF-1α expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1α expression in tumor tissues had lower overall survival rate than patients with negative HIF-1α expression. It was suggested that HIF-1α expression may be a prognostic biomarker and a potential therapeutic target for lung cancer.
Adenocarcinoma ; diagnosis ; genetics ; mortality ; pathology ; Biomarkers, Tumor ; genetics ; metabolism ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; genetics ; mortality ; pathology ; Carcinoma, Squamous Cell ; diagnosis ; genetics ; mortality ; pathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Lung Neoplasms ; diagnosis ; genetics ; mortality ; pathology ; Lymphatic Metastasis ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Prognosis ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Survival Analysis ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

OBJECTIVETo explore the relationship between DNA mismatch repair (MMR) and clinicopathologic features and prognosis in patients with stages II and III colon cancers.

METHODSThe clinical and pathological data of 440 patients with stage II/III colon cancer after radical resection were retrospectively reviewed and analyzed. Immunohistochemical staining was used to assess the expression of MMR proteins (MLH1, MSH2, MSH6 and PMS2), and the correlation between DNA MMR and clinicopathological features and prognosis of colon cancers was analyzed.

RESULTSOf the 440 tumor samples tested for DNA mismatch repair status, 90 (20.5%) demonstrated defective DNA mismatch repair and 350 (79.5%) had proficient DNA mismatch repair. Defective DNA mismatch repair (dMMR) was associated with young patients (≤ 60), proximal colon cancer, stage II, poorly differentiated adenocarcinoma and mucinous adenocarcinoma (P<0.05 for all). Among the 440 patients, 126 (28.6%) cases had recurrence or metastasis and 93 (21.1%) died during the median follow-up of 61.0 months. The five-year disease-free survival (DFS) rate was 82.2% among the patients with tumor exhibiting dMMR, significantly higher than that in patients with tumors exhibiting pMMR (68.9%, P=0.02). The univariate and mutlivariate analyses showed that the MMR status is an independent factor affecting 5-year disease-free survival and overall survival (OS) in colon cancer patients (P<0.05 for both).

CONCLUSIONSDefective DNA mismatch repair (dMMR) is associated with patients with proximal colon cancer, stage II and poorly defferentiated adenocarcinoma and mucinous adenocarcinoma. The prognosis for patients with dMMR is better than those with pMMR. dMMR may be a useful biomarker for the prognosis of colon cancer.

Adaptor Proteins, Signal Transducing ; metabolism ; Adenocarcinoma ; genetics ; metabolism ; mortality ; pathology ; Adenocarcinoma, Mucinous ; genetics ; metabolism ; mortality ; pathology ; Adenosine Triphosphatases ; metabolism ; Age Factors ; Analysis of Variance ; Colonic Neoplasms ; genetics ; metabolism ; mortality ; pathology ; DNA Mismatch Repair ; DNA Repair Enzymes ; metabolism ; DNA-Binding Proteins ; metabolism ; Disease-Free Survival ; Humans ; Mismatch Repair Endonuclease PMS2 ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; metabolism ; Neoplasm Recurrence, Local ; Nuclear Proteins ; metabolism ; Prognosis ; Retrospective Studies ; Survival Rate

BACKGROUND/AIMS: Oxidative stress results in protein oxidation and is implicated in carcinogenesis. Sulfiredoxin (Srx) is responsible for the enzymatic reversal of inactivated peroxiredoxin (Prx). Nuclear factor E2-related factor 2 (Nrf2) binds to antioxidant responsive elements and upregulates the expression of Srx and Prx during oxidative stress. We aimed to elucidate the biological functions and potential roles of Srx in lung cancer. METHODS: To study the roles of Srx and Prx III in lung cancer, we compared the protein levels of Nrf2, Prxs, thioredoxin, and Srx in 40 surgically resected human lung cancer tissues using immunoblot and immunohistochemical analyses. Transforming growth factor-beta1, tumor necrosis factor-alpha, and camptothecin treatment were used to examine Prx III inactivation in Mv1Lu mink lung epithelial cells and A549 lung cancer cells. RESULTS: Prx I and Prx III proteins were markedly overexpressed in lung cancer tissues. A significant increase in the oxidized form of a cysteine sulfhydryl at the catalytic site of Prxs was found in carcinogenic lung tissue compared to normal lung tissue. Densitometric analyses of immunoblot data revealed significant Srx expression, which was higher in squamous cell carcinoma tissue (60%, 12/20) than in adenocarcinoma (20%, 4/20). Also, Nrf2 was present in the nuclear compartment of cancer cells. CONCLUSIONS: Srx and Prx III proteins were markedly overexpressed in human squamous cell carcinoma, suggesting that these proteins may play a protective role against oxidative injury and compensate for the high rate of mitochondrial metabolism in lung cancer.
Adenocarcinoma/*enzymology/genetics/mortality/pathology ; Animals ; Antineoplastic Agents, Phytogenic/pharmacology ; Blotting, Western ; Camptothecin/pharmacology ; Carcinoma, Squamous Cell/*enzymology/genetics/mortality/pathology ; Cell Line, Tumor ; Humans ; Immunohistochemistry ; Lung Neoplasms/*enzymology/genetics/mortality/pathology ; Mink ; NF-E2-Related Factor 2/*metabolism ; Oxidoreductases Acting on Sulfur Group Donors/genetics/*metabolism ; Peroxiredoxin III/*metabolism ; Peroxiredoxins/metabolism ; Prognosis ; RNA Interference ; Reactive Oxygen Species/metabolism ; Transfection ; Transforming Growth Factor beta1/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Up-Regulation

Adenocarcinoma ; blood supply ; metabolism ; mortality ; secondary ; Adult ; Aged ; Female ; Humans ; Lymphatic Metastasis ; Male ; Microcirculation ; Middle Aged ; Neovascularization, Pathologic ; metabolism ; pathology ; Prognosis ; RNA, Messenger ; biosynthesis ; genetics ; Receptors, Cell Surface ; biosynthesis ; genetics ; Receptors, Urokinase Plasminogen Activator ; Stomach Neoplasms ; blood supply ; metabolism ; mortality ; pathology ; Survival Rate ; Vascular Endothelial Growth Factor A ; metabolism