Cancer Biomarkers - Volume 8, issue 1

Authors: Elsberger, Beatrix | Lankston, Louise | Orange, Clare | Underwood, Mark A. | Edwards, Joanne

Article Type: Research Article

Abstract: Hypoxia inducible factor-1 alpha (HIF-1α) is known as an important transcription factor in endocrine tumours. It is elevated in hypoxic tumour microenvironment, increasing angiogenesis and enabling tumour cells to enter the circulation. We therefore hypothesised that patients with advanced prostate cancer disease have high tumoural HIF-1α xpression and worse disease specific survival. Aim of this study was to assess expression of HIF-1α in prostate cancer specimens taken before and after castrate resistance to address its cellular location and to examine if this is associated with clinicopathological features and clinical outcome of the particular prostate cancer cohort. 50 pairs …of hormone naive and castrate resistant prostate cancer specimens were analysed employing tissue microarray technology. Immunohistochemistry was performed using an antibody to HIF-1α. HIF-1α expression was observed in both, cytoplasm and nucleus. Cytoplasmic HIF-1α expression correlated positively with metastases at diagnosis (p=0.005), whereas nuclear HIF-1α expression correlated with metastases at relapse (p=0.041). Cytoplasmic and nuclear HIF-1α expression did not change from hormone naive to hormone castrate resistant tumours. No significant association was observed in this study between tumoural HIF-1α expression, biochemical relapse and patient survival. HIF-1α was associated with the presence of metastases at time of diagnosis and time of relapse. HIF-1α is likely to play a role in progressive prostate cancer. Show more

Keywords: Hypoxia inducible factor-1 alpha protein, prostate cancer, biochemical relapse, disease specific survival, immunohistochemistry

DOI: 10.3233/DMA-2011-0805

Citation: Cancer Biomarkers, vol. 8, no. 1, pp. 1-9, 2011

Authors: Kostrzewska-Poczekaj, Magdalena | Giefing, Maciej | Jarmuz, Malgorzata | Brauze, Damian | Pelinska, Kinga | Grenman, Reidar | Bartochowska, Anna | Szyfter, Witold | Szyfter, Krzysztof

Article Type: Research Article

Abstract: Thirteen laryngeal squamous cell carcinoma cell lines were recently studied by array comparative genomic hybridization (array-CGH) in order to identify recurrent DNA copy number alterations in the tumor genome. A highly amplified region 22q11.2 was found in two of the thirteen cell lines. Two established oncogenes CRKL and MAPK1 are localized in this region, but only CRKL was amplified in both cell lines. Therefore, to check if amplification of either CRKL or MAPK1 genes may be important in the pathogenesis of laryngeal squamous cell carcinoma, the DNA copy number and mRNA expression were measured in a cohort of 17 …LSCC cell lines by quantitative real-time PCR (qPCR). For the CRKL gene gains of the copy number were found in 3/17 cell lines, while overexpression was found in 6/17 cell lines. Gains in the copy number for the MAPK1 gene were found in 1/17 cell lines, but overexpression was not detected in any cell line. A highly significant correlation between DNA copy number and expression for CRKL gene, but not for MAPK1 gene was established using the Pearson test. Thereafter, 46 primary samples of laryngeal cancer were tested by qPCR to check for possible gains in copy number of the CRKL gene. Gains were found in 3/46 cases. These results suggest that CRKL, but not MAPK1 is the target oncogene of the rare but recurrent amplification at 22q11.2 in laryngeal squamous cell carcinoma. Show more

DOI: 10.3233/DMA-2011-0814

Citation: Cancer Biomarkers, vol. 8, no. 1, pp. 11-19, 2011

Authors: Srivastava, Priyanka | Jaiswal, Praveen K. | Singh, Vibha | Mittal, Rama D.

Article Type: Research Article

Abstract: p53 is a major orchestrator of cellular response to a broad array of stress types by regulating apoptosis, cell cycle arrest, etc. A few polymorphic sites, one at codon72 of exon4, intron3 16bpdel/ins, intron6G>A have been studied with regard to Bladder cancer (BC) risk in North Indians. Genotypes were assessed in hospital-based case-control study comprising of 200BC cases, 265healthy controls. After extraction of genomic DNA from blood, genotyping was done using PCR Restriction Fragment Length Polymorphism. Individuals with p53R72P G>C, CC genotype demonstrated marginally reduced risk of BC (p=0.053, OR=0.29, 95%CI = 0.08–1.02). In intron3 16bp-ins/del, I allele, its carrier …(D/I+I/I) were at higher risk (p = 0.012, OR = 1.52, 95%CI = 1.09-2.11; p = 0.040, OR = 1.55, 95%CI = 1.02–2.38). Haplotypes p53 intron6 G-R72P G-intron3 I (GGI) and p53 intron6 A-R72P G-intron3 D (AGD) (p < 0.001, Pc= 0.008, OR= 2.44, 95%CI =1.52–3.93; p = 0.006, Pc= 0.048, OR = 1.89, 95%CI = 1.20–2.98 respectively), were also found to be associated with increased risk. intron6G>A, intron3 16bp ins/del gene-combination (GG-I/D, GA-I/I) showed significant association with BC. In R72P G>C, GC was associated with reduced risk of recurrence (HR = 0.29, p = 0.022, 95%CI = 0.11–0.84) in patients receiving BCG treatment thus showing increased recurrence-free survival(GC/GG = 49/30months;log rank = 0.008). p53R72PG>C, intron3-16bp duplication polymorphism are potentially important, clinically relevant genetic markers contributing to BC susceptibility. Kaplan-Meier analysis of BC patients harboring the R72P GC showed significantly longer recurrence free survival with adjuvant immunotherapy. Show more

Keywords: Bacillus Calmette-Guérin, bladder cancer, haplotypes, p53, recurrence free survival

DOI: 10.3233/DMA-2011-0816

Citation: Cancer Biomarkers, vol. 8, no. 1, pp. 21-28, 2011

Authors: Pakiz, Maja | Potocnik, Uros | But, Igor | Mujezinovic, Faris

Article Type: Research Article

Abstract: Objective: The mutant genotype GG of the CYP17A1 gene polymorphism has been linked to higher levels of serum estradiol and thus might be associated with steroid-hormone dependent tumors. We decided to assess an association of CYP17A1 polymorphism with uterine leiomyomas (ULM) and multiple ULM by conducting a meta-analysis and subgroup analysis. Methods: We searched the HuGE Navigator and PubMed databases using the terms “leiomyoma” and “CYP17A1” for articles published by October 1, 2010. Our article in press was added. The selection criteria were (i) cases having ULM, (ii) controls showing no ULM from the same ethnic group, (iii) …cases and controls not overlapping. The subgroup analysis included cases having multiple ULM, predisposing black women mostly present with multiple ULM. Pooled risk ratio was calculated using χ 2 statistic. Results: Five papers fulfilled the selection criteria for meta-analysis and two papers for the subgroup analysis. The meta-analysis revealed no association of CYP17A1 polymorphism with all ULM. A high pooled risk ratio for multiple ULM was associated with the presence of mutant genotype GG (RR 3.25). Conclusion: CYP17A1 polymorphism may be associated with multiple ULM but not with all ULM. The future research might enable us to predict the course of the disease. Show more

Keywords: Uterine leiomyomas, CYP17A1 gene polymorphism, multiple uterine leiomyoma

DOI: 10.3233/DMA-2011-0817

Citation: Cancer Biomarkers, vol. 8, no. 1, pp. 29-34, 2011

Authors: Bejrananda, Tanan | Phukaoloun, Monlika | Boonpipattanapong, Teeranut | Wanitsuwan, Worawit | Kanngern, Samornmas | Sangthong, Rassamee | Sangkhathat, Surasak

Article Type: Research Article

Abstract: WT1 has been proven to be a prognostic marker and molecular target in various human cancers. In this study, we aimed to investigate the prognostic role of WT1 in colorectal cancers (CRCs). Archival tissue samples from 157 CRC cases who underwent curative surgery in our institute from February 1999 to May 2004 were subjected to WT1 expression studies using an immunohistochemistry technique. Number of positive staining per 500 tumor cells and staining intensities were analyzed against overall survival. Of 157 CRCs, 83 were colonic and 74 were rectal cancers. The mean follow-up period was 116 (range 77–145) months. Five-year and …seven-year OS rates were 60.9% and 52.8%, respectively. WT1 immunostaining was positive in 143 cases (91%). The median number of positive cells was 120 (range 0–420). Univariate analysis by Log-rank test showed that AJCC stage, tumor site (rectal cancer), number of positive cells > 120 and high staining intensity (score ++/+++) were significantly associated with poorer survival (p-value < 0.01). Five-year survival rates in cases with positive cells of > 120 cells and > 120 cells were 72.2% and 49.4%, respectively. Five-year survival in cases with staining intensity of ++ or more was 45.3%, compared with 69% in cases with intensity of less than ++. Multivariate regression analysis demonstrated that the staining intensity, high tumor stage and rectal site were independent factors indicating poorer survival. Our findings indicate that WT1 expression is a marker of poor prognosis in CRCs, independent of AJCC staging. Show more

DOI: 10.3233/DMA-2011-0822

Citation: Cancer Biomarkers, vol. 8, no. 1, pp. 35-42, 2011

Authors: Kallel, Rihab | Belguith-Maalej, Salima | Akdi, Abdelmounaim | Mnif, Mouna | Charfeddine, Ilhem | Galofré, Pere | Ghorbel, Abdelmonaim | ABID, Mohamed | Marcos, Ricard | Ayadi, Hammadi | Velázquez, Antonia | Kacem, Hassen Hadj

Article Type: Research Article

Abstract: FOXE1 polyalanine tract (poly-Ala) has been associated with thyroid dysgenesis. Recently, the SNP (rs1867277:-238G>A) within the FOXE1 5'UTR was involved in the genetic susceptibility to thyroid cancer (TC). In the aim to assess the influence of FOXE1 poly-Ala length on the genetic susceptibility to TC and autoimmune thyroid diseases (AITD), a case-control design (including 261 Tunisian AITD, 170 Spanish TC and respectively 171 and 218 matched healthy subjects) was performed. The effect of Ala length and rs1867277 alleles on FOXE1 expression was investigated by mRNA relative real time quantification on 8 papillary thyroid carcinoma (PTC) and 10 Graves' disease (GD) …genotyped thyroid biopsies. The fluorescent genotyping of poly-Ala polymorphism revealed nine alleles (from 12 to 22 repetitions). The association of poly-Ala polymorphism with AITD was rejected (Pc>0.05). However, a significant association was found with TC. In addition, the genotypic distributions revealed the predispositional effect of the 16/16 genotype (OR = 2.71; 95%CI: 1.36–5.42; p=0.001) and the protector effect of the 14/14 genotype (OR= 0.46; 95%CI: 0.29–0.72; p=0.003). The quantification studies reveal that FOXE1 transcripts were less abundant in PTC than GD samples. Moreover, FOXEI gene was 4,8 fold less expressed among PTC protected patients compared to homozygous 16/16-A/A. In conclusion, by exploring the poly-Ala polymorphism, we confirmed the involvement of FOXE1 gene in the genetic susceptibility to TC and we reported its down expression among PTC tissues. Show more

Keywords: AITD, thyroid carcinoma, Graves' disease, FOXE1, poly (Ala)

DOI: 10.3233/DMA-2011-0824

Citation: Cancer Biomarkers, vol. 8, no. 1, pp. 43-51, 2011