crossing96/oncoscreening huggingface dataset:
Status of involved lymph nodes and direction of metastatic lymphatic flow between submucosal and t2-4 thoracic squamous cell esophageal cancers.	BACKGROUND: Three-field lymph node dissection for thoracic esophageal cancer is associated with high morbidity and reduced quality of life after surgery. Consequently, minimized lymphadenectomy would be desirable, if appropriate. In the present study, we retrospectively analyzed the status of involved nodes and the direction of metastatic lymphatic flow from tumors into involved nodes to determine whether submucosal squamous cell esophageal cancers are potential candidates for minimized lymphadenectomy. METHODS: We enrolled 199 patients who received esophagectomy with extensive lymph node dissection between 1989 and 2005 and retrospectively analyzed their prognoses, distribution of solitary metastatic lymph nodes, and the direction of metastatic lymphatic flow from the tumor, taking into consideration tumor location and depth. RESULTS: Of these patients with submucosal cancers, 83% had 1 or 2 involved nodes, and their esophageal cancer-specific 5-year survival rate was 66%. Solitary lymph node metastasis did not occur in neck lymph nodes in lower thoracic submucosal esophageal cancers, and the direction of metastatic lymphatic flow from the tumor was almost always in one direction. By contrast, T2-4 cancers with 2-4 involved nodes had bidirectional metastatic lymphatic flow from the tumor. CONCLUSIONS: There was a difference in the status of lymph node metastasis and the direction of metastatic lymphatic flow from tumors into involved nodes between submucosal and T2-4 thoracic squamous cell esophageal cancers. This analysis may be useful for developing an approach to minimized lymphadenectomy for thoracic esophageal cancers.	esophagus
Overexpression of PLK1 is associated with poor survival by inhibiting apoptosis via enhancement of survivin level in esophageal squamous cell carcinoma.	PLK1 is essential for the maintenance of genomic stability during mitosis. In our study, we found that overexpression of PLK1 was an independent prognostic factor (RR=4.253, p=0.020) and significantly correlated with survivin, an antiapoptotic protein, in esophageal squamous cell carcinoma (ESCC). Reverse transcription-polymerase chain reaction and fluorescence in situ hybridization (FISH) revealed upregulation of PLK1 mRNA and amplification of PLK1 gene, respectively. Depletion of PLK1 activated the intrinsic apoptotic pathway, which was substantiated by loss of mitochondrial membrane potential, reduction of Mcl-1 and Bcl-2 as well as activation of caspase-9. Coimmunoprecipitation and confocal microscopy displayed that PLK1 was associated with survivin and PLK1 depletion led to downregulation of survivin. Cotransfection of survivin constructs could partially reverse PLK1-depletion-induced apoptosis. These data suggest that PLK1 might be a useful prognostic marker and a potential therapeutic target for ESCC. Survivin is probably involved in antiapoptotic function of PLK1.	esophagus
Interferon-inducible guanylate binding protein (GBP)-2: a novel p53-regulated tumor marker in esophageal squamous cell carcinomas.	TP53 mutations are common in esophageal squamous cell carcinomas (SCC). To identify biological markers of possible relevance in esophageal SCC, we (i) searched for genes expressed in a p53-dependent manner in TE-1, an esophageal SCC cell line expressing the temperature-sensitive TP53 mutant V272M, and (ii) investigated the expression of one of those genes, the interferon-inducible Guanylate Binding Protein 2 (GBP-2), in esophageal SCC tissues. Clontech Human Cancer 1.2 arrays containing 1,176 human cancer gene-related sequences were used to identify differentially expressed genes in TE-1 cells at permissive (32 degrees C) and nonpermissive (37 degrees C) temperatures. The expression of GBP-2 and IRF-1, its main transcriptional regulator, was analyzed by immunohistochemistry in a retrospective series of 41 esophageal SCC cases with a clear transition zone from noncancer, apparently normal epithelium to invasive cancer. The expression of the GBP-2 gene is consistently increased in TE-1 at 32 degrees C in a p53-dependent manner, as confirmed by inhibition of p53 expression by RNA interference. Increase in GBP-2 is accompanied by an increase in protein levels of IRF-1, the main transcriptional regulator of GBP-2, and in the formation of complexes between p53 and IRF-1. GBP-2 expression is significantly higher in esophageal SCC than in adjacent normal epithelium (p<0.01), in which GBP-2 staining is limited to the basal layer. Our results suggest that p53 up-regulates GBP-2 by cooperating with IRF-1. The association of GBP-2 expression with proliferative squamous cells suggests that GBP-2 may represent a marker of interest in esophageal SCC.	esophagus
Clinical and molecular characteristics of squamous cell carcinomas from Fanconi anemia patients.	Fanconi anemia is a recessively inherited disease that is characterized by congenital abnormalities, bone marrow failure, and a predisposition to develop cancer, particularly squamous cell carcinomas (SCCs) in the head and neck and anogenital regions. Previous studies of Fanconi anemia SCCs, mainly from US patients, revealed the presence of high-risk human papillomavirus (HPV) DNA in 21 (84%) of 25 tumors analyzed. We examined a panel of 21 SCCs mainly from European Fanconi anemia patients (n = 19 FA patients; 16 head and neck squamous cell carcinomas [HNSCCs], 2 esophageal SCCs, and 3 anogenital SCCs) for their clinical and molecular characteristics, including patterns of allelic loss, TP53 mutations, and the presence of HPV DNA by GP5+/6+ polymerase chain reaction. HPV DNA was detected in only two (10%) of 21 tumors (both anogenital SCCs) but in none of the 16 HNSCCs. Of the 18 tumors analyzed, 10 contained a TP53 mutation. The patterns of allelic loss were comparable to those generally found in sporadic SCCs. Our data show that HPV does not play a major role in squamous cell carcinogenesis in this cohort of Fanconi anemia patients and that the Fanconi anemia SCCs are genetically similar to sporadic SCCs despite having a different etiology.	esophagus
Hamster exhibits major differences in organ-specific metabolism of the esophageal carcinogen N-nitrosodiethylamine.	Nitrosamines are carcinogens that require metabolic activation by CYP enzymes in order to exert their carcinogenic effect. Species differences exist in their esophageal carcinogenic potency, with the rat being the most sensitive and the Syrian hamster a resistant species. In the latter, the liver is the main target organ. This difference does not apply to directly acting N-nitroso compounds, suggesting that tissue-specific metabolic activation is involved in hamster esophageal resistance to nitrosamines. We have previously shown that Cytochrome P450 2A3 (CYP2A3) is responsible for N-nitrosodiethylamine activation in the rat esophagus. In order to find a mechanistic explanation for the resistance of hamster esophagus for nitrosamines, we have compared the metabolism of NDEA between esophagus and liver of the hamster. Hamster esophagus is capable of activating NDEA (K(m)=1.02+/-0.44microM and V(max)=1.96+/-0.26nmol acetaldehyde/min/mg microsomal protein). However, the hamster liver showed a 40-fold higher catalytic efficiency (V(max)/K(m)) towards NDEA metabolism compared with its esophagus. Hamster esophagus expresses CYP2A8, CYP2A9 and CYP2A16, but not CYP2E1. An antibody against human CYP2A6 was able to inhibit NDEA metabolism in hamster esophageal, but not liver microsomes. Our results suggest that in the hamster esophagus, but not in the liver, most of the NDEA is metabolized by CYP2A enzymes, but with a rather poor efficiency when compared to the liver. This is in accordance with previous results showing that for the hamster, the main target organ of NDEA is the liver.	esophagus
Cigarette smoking, body mass index, gastro-esophageal reflux disease, and non-steroidal anti-inflammatory drug use and risk of subtypes of esophageal and gastric cancers by P53 overexpression.	A number of risk factors for esophageal and gastric cancers have emerged, yet little is known whether risk factors map to molecular tumor markers such as overexpression of the tumor suppressor TP53. Using a US multicenter, population-based case-control study (170 cases of esophageal adenocarcinomas, 147 gastric cardia adenocarcinomas, 220 non-cardia gastric adenocarcinomas, and 112 esophageal squamous cell carcinomas), we examined whether the risk associated with cigarette smoking, body mass index (BMI), gastroesophageal reflux disease (GERD), and non-steroidal anti-inflammatory drug (NSAID) use varied by P53 overexpression. We defined P53 overexpression through immunohistochemistry of paraffin-embedded tumor tissues, using cutpoints based on percent of cells positive. Polytomous logistic regression was used to assess differences between each case group (defined by tumor subtype and P53 expression) and the control group by risk factors. The proportion of cases overexpressing P53 by tumor subtype was 72% for esophageal adenocarcinoma, 69% for gastric cardia adenocarcinoma, 52% for non-cardia gastric adenocarcinoma, and 67% for esophageal squamous cell carcinoma. For most tumor subtypes, we found little difference in risk factors by tumor P53 overexpression. For non-cardia gastric cancer however, an association with cigarette smoking was suggested for tumors that do not overexpress P53, whereas larger BMI was related to adenocarcinomas that overexpress P53 versus no overexpression. Overall, this study did not find a clear relationship between P53 protein overexpression and the known risk factors for subtypes of esophageal and gastric cancers. Further research on these tumors is needed to identify molecular markers associated with variations in the risk factor profiles.	esophagus
Cell proliferation, cell cycle abnormalities, and cancer outcome in patients with Barrett's esophagus: a long-term prospective study.	PURPOSE: Elevated cellular proliferation and cell cycle abnormalities, which have been associated with premalignant lesions, may be caused by inactivation of tumor suppressor genes. We measured proliferative and cell cycle fractions of biopsies from a cohort of patients with Barrett's esophagus to better understand the role of proliferation in early neoplastic progression and the association between cell cycle dysregulation and tumor suppressor gene inactivation. EXPERIMENTAL DESIGN: Cell proliferative fractions (determined by Ki67/DNA multiparameter flow cytometry) and cell cycle fractions (DNA content flow cytometry) were measured in 853 diploid biopsies from 362 patients with Barrett's esophagus. The inactivation status of CDKN2A and TP53 was assessed in a subset of these biopsies in a cross-sectional study. A prospective study followed 276 of the patients without detectable aneuploidy for an average of 6.3 years with esophageal adenocarcinoma as an end point. RESULTS: Diploid S and 4N (G(2)/tetraploid) fractions were significantly higher in biopsies with TP53 mutation and loss of heterozygosity. CDKN2A inactivation was not associated with higher Ki67-positive, diploid S, G(1), or 4N fractions. High Ki67-positive and G(1)-phase fractions were not associated with the future development of esophageal adenocarcinoma (P=0.13 and P=0.15, respectively), whereas high diploid S-phase and 4N fractions were (P=0.03 and P<0.0001, respectively). CONCLUSIONS: High Ki67-positive proliferative fractions were not associated with inactivation of CDKN2A and TP53 or future development of cancer in our cohort of patients with Barrett's esophagus. Biallelic inactivation of TP53 was associated with elevated 4N fractions, which have been associated with the future development of esophageal adenocarcinoma.	esophagus
The galanin signaling cascade is a candidate pathway regulating oncogenesis in human squamous cell carcinoma.	To identify putative biomarkers in squamous cell carcinoma (SCC), a survey of parallel chromosomal alterations and gene expression studies in 10 SCC cell lines were performed using array-comparative genomic hybridization (CGH) and oligo-microarray techniques. The most frequent changes were gains of 11q13.1-13.3 and losses of 18q12.1-23 in SCC. Furthermore, the expression levels of the sets of genes at both these loci in SCC were measured using microarray analysis. By combining the array-CGH with the microarray data, 10 genes at 11q13.1-13.3 and 6 genes at 18q12.1-23 whose expression correlated with chromosomal alterations were identified. To verify the expression levels of the identified genes, we used expression analysis data derived from our earlier study of clinical specimens. In clinical samples, six genes (GAL, GSTP1, MRPL11, MRPL21, SF3B2, and YIF1A) at 11q13.1-13.3 and one gene (GALR1) at 18q23 showed a significant difference between normal and tumor samples. GAL, coding for the neuropeptide galanin, and GALR1, a galanin receptor, were identified as candidate genes of oncogenesis in SCC. The expression levels of GAL, GALR1, GALR2, and GALR3 were confirmed by real-time PCR. The expression ratio between GAL and GALR1 showed a significant negative correlation. GALR1 is a G-protein-coupled receptor that activates GTP-binding proteins to trigger signaling cascades such as the mitogen-activated protein kinase pathway, and is a well-established mitogenic pathway. This further supports the hypothesis that the genes involved in the GAL signaling cascade are candidates for regulation of oncogenesis in SCC.	esophagus
PINCH expression and its significance in esophageal squamous cell carcinoma.	Particularly interesting new cysteine-histidine rich protein (PINCH), as a newly discovered protein of LIM family members, may play a role in signal transduction of integrin and growth factor, and involved in the incidence and development of tumors. PINCH protein is overexpressed in tumor-associated stroma of several types of tumors. However, there is no study of the PINCH in esophageal cancer, therefore we investigated PINCH expression in esophageal squamous cell carcinomas and its clinicopathological significance in the patients. PINCH expression was immunohistochemically examined in 20 normal esophageal samples and 64 esophageal squamous cell carcinomas. The results showed that PINCH expression in the stroma of cancers was heterogeneous, and its positive rate (56%) was higher than that of normal esophageal mucosa (5%, p<0.0001). The stronger staining was observed at the invasive edge of tumor when compared to the inner area of tumor. The rate of positive PINCH (90%) in the cases with lymph node metastasis was higher than that (41%) in the cases without metastasis (p<0.0001). PINCH expression was not correlated with patients' gender, age, tumor location, size and differentiation (p>0.05). The results suggest that PINCH protein may be a marker of tumor associated-stroma involving tumor development, and predicting the ability of invasion and metastasis of esophageal squamous cell carcinoma.	esophagus
Prognostic significance of global histone modifications in resected squamous cell carcinoma of the esophagus.	Patterns of global histone modifications have been recently suggested as outcome predictors in cancer patients. To date, there has been no report on the prognostic significance of global histone modifications in esophageal squamous cell carcinoma. We investigated the role of global histone modification as outcome predictor in patients undergoing esophagectomy for esophageal squamous cell carcinoma. A retrospective clinicopathologic analysis was undertaken of 97 patients with esophageal squamous cell carcinoma who recovered from esophagectomy. Immunohistochemical expression of five histone modification markers, acetylated histone 3 lysine 18 (H3K18Ac), acetylated histone 4 lysine 12 (H4K12Ac), dimethylated histone 4 arginine 3 (H4R3diMe), dimethylated histone 3 lysine 4 (H3 K4diMe), and trimethylated histone 3 lysine 27 (H3K27triMe) was assessed in paraffin-embedded tumor samples. Results were analyzed in relation to patients' clinicopathologic parameters. There was a positive relationship between tumor differentiation and H3K18Ac (P<0.001), H4R3diMe (P=0.003), and H3K27triMe (P<0.001). Expression of H3K27triMe correlated positively with nodal (N) status (P=0.012) and stage (P=0.025). Univariate analysis showed that better survival in patients with low expression of H3K18Ac (P=0.038) and H3K27triMe (P=0.003). Multivariate analysis showed that nodal status, metastasis status (M), and expression of H3K27triMe predicted survival independently (P<0.001, P=0.016, and 0.048, respectively). Low expression of H3K18Ac and H3K27triMe correlated with better prognosis of patients with esophageal squamous cell carcinoma, especially for those of early stages. We hypothesize that expression of H3K27triMe may be considered as a significant survival predictor for patients with esophageal squamous cell carcinoma.	esophagus
Minimally invasive esophagectomy for cancer.	Since 1992, various combinations of thoracoscopy (VATS), laparoscopy or hand-assisted thoracolaparoscopy have been used for 'minimally invasive' cancer esophagectomy (MIE). Despite widespread current use, indications and potential benefits of the many technical approaches remain controversial. A systematic literature search was conducted until June 2007. Out of 128 publications, 46 original series (1932 patients) met the inclusion criteria and were analyzed for surgical and oncological outcome. No prospective controlled study has compared any MIE technique to another or to open surgery. Most publications are retrospective series of highly selected patients, mostly excluding high-risk patients and locally advanced (T3) tumors. Altogether, the overall conversion rate was 5.9%, mortality 2.9% and morbidity 46%, many papers reporting only major complications. Overall, rates for pulmonary complications were 22%, leakage 8.8% and vocal cord palsy 7.1%. Fifteen tracheo-bronchial injuries or fistulas (1% of all VATS cases) were reported. Laparoscopy and VATS were combined in 11 series (609 patients, 4.7% conversions, 2.4% mortality). VATS combined with (mini)-laparotomy was reported in 14 papers (743 patients, 6.3% conversions, 2.4% mortality). Laparoscopy combined with right thoracotomy was reported in four papers (147 patients, 5.4% conversions, 2% mortality). Laparoscopic transhiatal resections were reported in 17 papers (433 patients, 7% conversions, 4.6% mortality). Overall morbidity rates for these four approaches were 43%, 47.6%, 51.6% and 46%, respectively. Data on oncological outcome are scarce. Lymph node retrieval (median of all series: 14 nodes, range 5-62) was mostly inferior to open surgery standards and follow-up too short to draw definitive conclusions regarding long-term survival. Based on the available literature, the morbidity and mortality of MIE is substantial and not inferior to radical open esophagectomy in experienced centers. Many different operative techniques for MIE have been reported without obvious superiority for any of them. The term 'minimally invasive' is not supported by hitherto reported results. Selection bias and huge variability in extent of resection and lymphadenectomy impair comparisons of different MIE techniques. Oncological outcome of MIE remains largely unknown by lack of good quality data and selection bias. MIE remains an investigational and still evolving treatment for invasive cancer.	esophagus
Primary oesophageal Ki (CD30)-positive ALK+ anaplastic large cell lymphoma of T-cell phenotype.	Primary oesophageal lymphoma is a very rare entity, with fewer than 30 reported cases worldwide. It represents an important cause of dysphagia. Most of the oesophageal lymphomas are diffuse large B-cell type, with only one reported case of anaplastic large cell lymphoma (ALCL) of T-cell phenotype. Primary oesophageal lymphomas that are not associated with an immunocompromised state tend to affect elderly patients. We describe the first case of primary oesophageal Ki (CD30)-positive ALK+ALCL of T-cell phenotype in a 34-year-old immunocompetent woman, who presented with a two-year history of dysphagia. She was treated with chemotherapy and endoscopic oesophageal dilations and stenting, resulting in complete remission of the lymphoma and resolution of the dysphagia. She then underwent autologous peripheral blood haematopoietic stem cell transplantation and remained disease-free two years after the diagnosis.	esophagus
Expression analysis of Barrett's esophagus-associated high-grade dysplasia in laser capture microdissected archival tissue.	PURPOSE: Identifying genes differentially expressed in nondysplastic BE (NDBE) from those expressed in high-grade dysplasia (HGD) should be of value in improving our understanding of this transition and may yield new diagnostic and/or prognostic markers. The aim of this study was to determine the differential transcriptome of HGD compared with NDBE through gene microarray analysis of epithelial cells microdissected from archival tissue specimens. EXPERIMENTAL DESIGN: Laser capture microdissection was used to isolate epithelial cells from adjacent inflammatory and stromal cells. Epithelial mRNA was extracted from areas of NDBE and HGD in matched biopsies from 11 patients. mRNA was reverse transcribed and applied on Affymetrix cDNA microarray chips customized for formalin-exposed tissue. For a subset of these genes, differential gene expression was confirmed by real-time PCR and immunohistochemistry. RESULTS: There were 131 genes overexpressed by at least 2.5-fold in HGD versus NDBE and 16 genes that were underexpressed by at least 2.5-fold. Among the overexpressed genes are several previously shown to be increased in the neoplastic progression of BE, as well as novel genes such as lipocalin-2, S100A9, matrix metallopeptidase 12, secernin 1, and topoisomerase IIalpha. Genes decreased in dysplastic epithelium include MUC5AC, trefoil factor 1 (TFF1), meprin A, and CD13. Real-time PCR validated the changes in expression in 24 of 28 selected genes. Immunohistochemistry confirmed increased protein expression for topoisomerase IIalpha, S100A9, and lipocalin-2 and decreased expression of TFF1 across the spectrum of BE-associated dysplasia from NDBE through adenocarcinoma. CONCLUSIONS: This is the first study to identify epithelial genes differentially expressed in HGD versus NDBE in matched patient samples. The genes identified include several previously implicated in the pathogenesis of BE-associated dysplasia and new candidates for further investigation.	esophagus