Cancer Biomarkers - Volume 5, issue 1

Authors: Mohammadizadeh, Fereshteh | Ghasemibasir, Hamidreza | Rajabi, Parvin | Naimi, Azar | Eftekhari, Amin | Mesbah, Alireza

Article Type: Research Article

Abstract: Background: Down-regulation of the epithelial cell-cell adhesion molecule E-cadherin is frequently associated with tumor formation and progression in breast cancer. The aim of this study is the assessment of relationship between E-cadherin expression and routine prognostic biomarkers as well as grading and lymph node status in breast invasive ductal carcinomas. The associations between co-expression of E-cadherin and other biomarkers on one hand and grading, proliferating index and lymph node status on the other have also been evaluated. Objective: To evaluate the correlation of E-cadherin expression and routine immunohistochemistry panel in breast invasive ductal carcinoma. Methods: 108 …formalin-fixed and paraffin-embedded breast cancer specimens (of invasive ductal carcinoma “NOS” type) from the pathology archive of Alzahra hospital(Isfahan, Iran) which had been studied for expression of routine molecular biomarkers were selected. E-cadherin expression was detected by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of cells showing E-cadherin staining. Results: No association was found between E-cadherin alteration and ER, PR, p53, Ki67 and HER2/neu status of breast cancer. However, E-cadherin alteration showed a significant difference between grading and also lymph node groups. There was no association between co-expression of E-cadherin/ER, E-cadherin/PR, E-cadherin/Her-2neu, E-cadherin/p53 and Her-2neu/p53 on one hand and Ki67 status and tumor grade on the other. Co-expressions of E-cadherin/Her-2neu and E-cadherin/p53 showed significant difference in lymph node groups. Conclusion: We found that E-cadherin alteration in breast cancer has an association with other important prognostic factors. Evaluation of E-cadherin status can help, independently or in addition to conventional biological prognostic markers, to identify prognosis of breast cancer. Show more

Keywords: Breast cancer, E-cadherin, immunohistochemistry

DOI: 10.3233/CBM-2009-0551

Citation: Cancer Biomarkers, vol. 5, no. 1, pp. 1-8, 2009

Authors: Man, Yan-Gao | Schwartz, Arnold | Levine, Paul H. | Teal, Christine | Berg, Patricia E.

Article Type: Research Article

Abstract: Our previous studies revealed that beta protein 1 (BP1) was barely detectable in normal human breasts, but was seen in 21%, 46%, and 81% of hyperplastic, in situ, and invasive breast lesions, respectively. Our current study attempted to assess BP1 expression in inflammatory breast cancer (IBC), a very aggressive subtype of breast cancers characterized by extensive lympho-vascular invasion and involvement of dermal lymphatics. Paraffin-embedded tissue sections from 45 cases of IBC (nine with paired metastatic lymph nodes) and different controls were assayed immunohistochemically for BP1 expression. Positive BP1 immunoreactivities were present in all IBC cases. Strikingly, all cancer cells metastasized …to lymph nodes and cells within lymphatic channels were uniformly and strongly immunoreactive to BP1. The percentage of BP1 positive cells and the intensity of BP1 immunostaining in IBC cases were significantly greater than those in non-IBC cases. Our findings suggest that BP1 may possess properties of onco-proteins that promote tumor progression, invasion, and metastasis, representing a putative signature marker for IBC and tumor aggressiveness. Show more

Keywords: BP1, homeobox gene, inflammatory breast cancer, tumor invasion, metastasis

DOI: 10.3233/CBM-2009-0563

Citation: Cancer Biomarkers, vol. 5, no. 1, pp. 9-17, 2009

Authors: Haghpanah, Vahid | Khalooghi, Keinoosh | Adabi, Khadijeh | Amiri, Parvin | Tavangar, Seyed Mohammad | Amirzargar, Ali | Ghaffari, Hamidollah | Yazdani, Nasrin | Nikbin, Behrooz | Larijani, Bagher | Amoli, Mahsa M.

Article Type: Research Article

Abstract: Objective: Papillary thyroid carcinoma (PTC) is the most frequent types of thyroid malignancies. Several genes may be involved in susceptibility of thyroid cancer including Human Leukocyte Antigens (HLA). The association of thyroid carcinoma with HLA alleles has been previously studied in other populations and certain HLA alleles were shown to be either predisposing or protective. The aim of this study was to determine the association between HLA-C allele frequencies and papillary thyroid carcinoma in an Iranian population. Design: HLA-Cw allele frequencies were determined in patients with papillary thyroid carcinoma (N = 54) and non-related healthy controls (N = …91) using PCR-SSP. Main Outcome: We found that HLACw*4 and HLACw*15 allele frequencies were significantly higher in our patients compared to the controls [P = 10 − 4 , OR; 12.5, 95% CI 2.6–116.9) and [P = 10 − 4 , OR; 24.7, 95% CI (3.6–1058) respectively]. Coclusions: Our results revealed certain HLA-C alleles are predisposing factors in papillary thyroid carcinoma in Iranian population. This confirms the previous findings for association between HLA-C alleles and differentiated carcinomas in other populations. Show more

Keywords: Genetics, HLA, papillary carcinoma, thyroid, epidemiology

DOI: 10.3233/CBM-2009-0564

Citation: Cancer Biomarkers, vol. 5, no. 1, pp. 19-22, 2009

Authors: Ben-Izhak, Ofer | Laster, Zvi | Akrish, Sharon | Muska, Egon | Gan, Shlomit | Nagler, Rafael M.

Article Type: Research Article

Abstract: Salivary malignancies are rare, heterogeneous, unpredictable in their clinical behavior and seldom studied. This study focused on examining the expression of mutated p53, the most prevalent mutated gene related to human cancer, in a rather large cohort of salivary malignancies (n = 70) and for a prolonged period (20 years). P53 was found to be a most powerful predictor for poor survival and more so when the tumor concurrently expressed TUNEL and heparanase markers, dramatically dropping the survival probability of the patients to 0! Survival probability at 6 years for patients with tumors stained negatively vs. positively for p53, TUNEL …and heparanase was 100% vs. 49% while at 18 years this probability dropped to 67% vs. 0%, respectively (p = 0.023). Significant correlation rates were found between age and poor survival, age and p53, and p53 and other co-existing malignancies. These findings support mutated p53 as a prognostic predictor and a pivotal player in salivary carcinogenesis. Significantly more extensive therapy applied to salivary p53-positive patients did not improve mortality rate, questioning the justification for such extensive therapy and emphasizing the need to understand p53, TUNEL and heparanase biological pathways and develop additional therapeutic tools for fighting salivary cancer. Show more

Keywords: p53, prognosis, malignancies, cancer, salivary glands

DOI: 10.3233/CBM-2009-0567

Citation: Cancer Biomarkers, vol. 5, no. 1, pp. 23-31, 2009

Authors: Suman, G. | Jamil, Kaiser | Suseela, K. | Vamsy, M. CH.

Article Type: Research Article

Abstract: Human Cytochrome P450 3A4 is a major P450 enzyme in the liver and gastrointestinal tract. It plays an important role in the metabolism of a wide variety of drugs, some endogenous steroids, and harmful environmental contaminants. To investigate the interindividual variation in CYP3A4 levels we have carried out a study on the genetic polymorphism of 100 breast cancer subjects using fine needle aspiration cytology (FNAC) sampling procedure. DNA was extracted from all the samples and PCR was carried out for detecting the CYP3A4 gene polymorphisms. We selected exon-7 and 10 which are present on the 5’-flanking coding region of the …gene using the respective primers for PCR followed by direct automated sequencing method for detecting the mutations. These mutations were compared to the wild type sequence structures obtained from GenBank database (accession no. AF209389). We found two novel point mutations which are heterozygous mutant alleles. The two variant alleles were Ile222Arg and Phe175Val occurring in coding region of exon-7. Ile222Arg mutation was found in 3 malignant cases whereas Phe175Val mutation was found in 4 malignant cases. This is the first report of these two novel point mutations in CYP3A4 gene. These mutations in the gene in respective patients were found to relate to drug response in invasive ductal carcinomas of breast cancer. Show more

Keywords: Cytochrome P450, genetic polymorphism, PCR, point mutations, sequencing

DOI: 10.3233/CBM-2009-0569

Citation: Cancer Biomarkers, vol. 5, no. 1, pp. 33-40, 2009

Authors: Jensen, L.B. | Bartlett, J.M.S. | Witton, C.J. | Kirkegaard, T. | Brown, S. | Müller, S. | Campbell, F. | Cooke, T.G. | Nielsen, K.V.

Article Type: Research Article

Abstract: Uncontrolled growth of cancer cells can be related to dysfunctional cell cycle control, including entry into S-phase, initiating cell division. Cyclin CCND3 and CCNE1 along with CDK2 and CDK6 regulate this checkpoint, and genetic changes, detectable by fluorescence in situ hybridization, are hypothesized to increase the aggressiveness of breast cancer, thereby influencing patient survival. Genomic change was investigated in 106 primary breast cancer samples, where the combined gene copy number changes in one of these four cell cycle regulatory factors was observed in 22% of the 98 tumors of successful analysis, distributed with 15 deletions and 7 amplifications. A trend …towards decreased survival was observed with the aberrations, suggesting a prognostic potential of this set of markers, which was supported by an association with tumor grade. For validation of the new set of FISH probes for the G1/S-phase cell cycle factors, two additional markers, frequently amplified in breast cancers, were included in this study: The G1/S phase control gene CCND1 and the proliferation marker MYC. Both markers were amplified in 14% and deleted in 5% of the cases. This is the first report of genomic deletions of MYC in breast cancer. Show more

Keywords: Amplification, breast cancer, CCND1, CCND3, CCNE1, CDK2, CDK6, deletion, fluorescence in situ hybridization, MYC

DOI: 10.3233/CBM-2009-0570

Citation: Cancer Biomarkers, vol. 5, no. 1, pp. 41-49, 2009

Authors: Ma, Wanlong | Kantarjian, Hagop | Zhang, Xi | Jilani, Iman | Sheikholeslami, Mohammad R. | Donahue, Amber C. | Ravandi, Farhad | Estey, Elihu | O'Brien, Susan | Keating, Michael | Giles, Francis J. | Albitar, Maher

Article Type: Research Article

Abstract: Roughly one-third of acute myeloid leukemia (AML) patients exhibit mutations in the nucleophosmin (NPM1) gene, and multiple studies have linked these mutations with a more favorable clinical outcome. We developed an assay for the detection of NPM1 mutations in peripheral blood plasma, and compared the results with clinical outcomes from a single institution. Analyzing plasma from previously untreated AML patients revealed NPM1 insertion mutations in 24 of 98 (24%) patients, with greater sensitivity than existing peripheral blood cell-based tests which showed positivity in only 22 of the 24 patients. Plasma testing allowed the detection of a novel 4 bp deletion …in NPM1 in one patient. Analysis of clinical data corroborated previous data linking NPM1 mutations with better clinical outcome. These data underline the significance of NPM1 in the biology and clinical behavior of AML, and demonstrate the reliability and efficacy of plasma-based testing for NPM1 mutations. Show more

Keywords: Acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), NPM1, mutation, plasma, survival, outcome

DOI: 10.3233/CBM-2009-0583

Citation: Cancer Biomarkers, vol. 5, no. 1, pp. 51-58, 2009