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Middle East Journal of Cancer - Volume:7 Issue: 1, Jan 2016

Middle East Journal of Cancer
Volume:7 Issue: 1, Jan 2016

  • تاریخ انتشار: 1394/11/15
  • تعداد عناوین: 8
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  • Nasrollah Erfani, Mohammad Javad Fattahi, Mohammad Hossein Dabbaghmanesh, Mohammad Mehrazmay, Ahmad Monabati, Akbar Rasekhi Kazerouni, Sassan Hafizi, Abbas Ghaderi Pages 1-7
    Background
    The phosphatidylinositol 3-kinase/Akt signaling pathway is recognized as a key driver of cancer cell survival and proliferation, and is often contingent upon an impairment of expression/function of the PTEN tumor suppressor, a negative regulator of this pathway. In addition, the cytoskeletal signaling protein Tensin 2 has also been implicated as a negative regulator of this pathway. However, the PI3K pathway remains to be fully characterized in clinical thyroid carcinomas. The aim of this study is to determine the expression of components of the PI3K pathway in neoplastic and normal tissue sections obtained from patients with thyroid carcinoma.
    Methods
    Tissues from 58 cases with thyroid carcinoma underwent immunohistochemistry for activated Akt (phosphorylated Akt, pAkt), Tensin 2 and PTEN.
    Results
    A total of 100% of thyroid cancerous tissues were positive for pAkt staining compared to 67.9% of normal tissues. In contrast, 46.8% of cancer tissues were positive for Tensin 2 compared to 61.7% of normal tissues. For PTEN, 82.8% of cancerous tissues and 67.2% of normal tissues stained positive for this protein. There were no associations between the expression levels of the molecules with the patients’ clinicopathological characteristics.
    Conclusion
    We have found evidence for an enhanced activation of the PI3K/Akt signaling pathway in clinical thyroid carcinoma tissues. This can be coupled with concomitant downregulation of Tensin 2. Further work is required to determine the relative significance of PTEN expression versus its activity in thyroid carcinoma in order to determine its role in the observed increased Akt activity.
    Keywords: PI3 kinase signaling pathway, pAkt, PTEN
  • Samia A. Ebeid, Nadia A. Abd El Moneim, Taha I. Hewala, Mahmoud A. Hemida, Gehan Shehata, Nafissa El, Taher Pages 9-20
    Background
    This study intends to determine the diagnostic and prognostic roles of hypermethylation of serum RASSF1A and protocadherin-10 promoters in females with breast cancer.
    Methods
    This study enrolled 80 breast cancer patients and 80 apparently normal healthy controls. The promoter methylation status of serum RASSF1A and PCDH10 genes was investigated using methylation specific PCR.
    Results
    We detected no hypermethylation of the two genes in serum DNA of normal healthy controls (100% specificity). Of the 80 patients, 50 (62.5% sensitivity) displayed hypermethylated RASSF1A, whereas 34 (42.5% sensitivity) showed hypermethylated PCDH10 and 64 (80% sensitivity) were hypermethylated in at least one of these two genes. A significant association existed between hypermethylated RASSF1A and axillary lymph node involvement. There was a significant association between hypermethylated PCDH10 and axillary lymph node involvement, tumor size and pathological grade. Hypermethylated RASSF1A and PCDH10 combination was significantly associated with axillary lymph node involvement and Her-2 expression. Patients with methylated RASSF1A or PCDH10 had significantly shorter survival rates compared to those with unmethylated RASSF1A or PCDH10.
    Conclusion
    Methylated RASSF1A is superior to methylated PCDH10 for diagnosis of breast cancer patients. Addition of methylated PCDH10 to methylated RASSF1A significantly improves the diagnostic accuracy of RASSF1A. The present study suggests that hypermethylated RASSF1A and PCDH10 may be independent prognostic indicators for disease-free survival in breast cancer patients.
    Keywords: Breast cancer, Hypermethylation, RASSF1A, PCDH10
  • Alia M. Attia, Abeer E. Ibrahim, Hussein Fakhry Pages 21-29
    Background
    We conducted a retrospective analysis to evaluate the impact of omission of supraclavicular radiotherapy on supraclavicular failure rate and treatment outcomes in N1 breast cancer patients with evaluation of prognostic factors that affected supraclavicular recurrence free survival.
    Methods
    This study analyzed the medical records of 109 patients with N1 breast cancer. All patients underwent surgery and received adjuvant chemotherapy without supraclavicular radiotherapy. Supraclavicular recurrence free survival, distant metastasis free survival, disease free survival, and overall survival were estimated using the Kaplan-Meier method and compared using log-rank analysis.
    Results
    After a median follow up period of 58 months, treatment failed in 31 patients (28.4%); patterns of failure consisted of locoregional (n=21, 19.3%), isolated supraclavicular (n=7, 6.4%), and distant metastasis (n=14, 12.8%). Survival rates at 5 years were as follows: supraclavicular recurrence free survival (84.9%), distant metastasis free survival (87.6%), and overall survival (86.4%). Univariate analysis revealed that the type of chemotherapeutic regimen was the only significant prognostic factor affected supraclavicular recurrence free survival; patients who received the cyclophosphamide, methotrexate, 5-fluorouracil chemotherapy regimen experienced lower supraclavicular recurrence free survival than those who received doxorubicin based and taxane based chemotherapy. Development of supraclavicular recurrence significantly lowered the 5-year overall survival (57.1%) and distant metastasis free survival (50%) rates compared to patients without supraclavicular recurrence who had an overall survival rate of 88.5% (P<0.0001) and distant metastasis free survival rate of 90% (P<0.0001).
    Conclusion
    Patients with N1 breast cancer had an overall supraclavicular recurrence of 6.4% which denoted that additional supraclavicular radiotherapy was unnecessary and could be given in N1 patients after surgery and an adjuvant CMF regimen. A prospective randomized trial would be needed to clarify the impact of supraclavicular radiotherapy on treatment outcome.
    Keywords: Breast cancer, N1 disease, Prognostic factors, Supraclavicular recurrence
  • Mehrdad Hashemi, Mehdi Pooladi, Solmaz Khaghani Razi Abad, Abolfazl Movafagh, Maliheh Entezari Pages 31-40
    Background
    Gliomas are the most frequently observed primary brain tumors. These tumors comprise a variety of different histological tumor types and malignancy grades. Oligodendrogliomas typically contain a rich network of branching capillaries. Approximately 50%-80% of oligodendrogliomas demonstrate a combined loss of chromosomes 1p and 19q. Oligodendrogliomas differ from neurocytomas in that they show a diffusely infiltrating pattern of spread that precludes surgical cure.
    Methods
    We evaluated extracted proteins from tumors and normal brain tissues for protein purity by the Bradford test and spectrophotometry. We separated proteins by two-dimensional gel electrophoresis. The spots were analyzed and compared using statistical data and MALDI-TOF/TOF. Protein clustering analyses were performed on the list of proteins deemed significantly altered in oligodendroglioma tumor tissues.
    Results
    On each analytical two-dimensional gel, we observed an average of 1328 spots. A total of 157 exhibited up-regulation of expression levels, whereas the remaining 276 spots had decreased expression in astrocytoma tumors relative to normal tissue. The results demonstrated that functional clustering and principal component analysis had considerable merit in aiding the interpretation of proteomic data.
    Conclusion
    Clustering methodology is a powerful data mining approach for initial exploration of proteomic data. The clustering results depend on parameters such as data preprocessing, between-profile similarity measurement and the dendrogram construction procedure.
    Keywords: Cluster, 2D, DIGE, Glioma, Proteomics, Oligodendroglioma
  • Nasrin Fouladi, Firouz Amani, Fariba Sadeghi Movahed, Hossein Ali, Mohammadi, Farhad Pourfarzi, Farhad Parvizi Pages 41-45
    Background
    This study examined perceived cognitive function in patients with breast cancer and determined the main predictors of changes in cognitive function following treatment.
    Methods
    The analytical cross-sectional study was performed in this study. 96 women receiving adjuvant treatment after surgery and who had already received adjuvant treatment were included in the study. The convenience sample was selected from the list of patients in Cancer Registry Center, private clinics and the Oncology Ward of Imam Khomeini Hospital in Ardabil, Iran. We used the Attentional Function Index to measure perceived cognitive function. SPSS version 16.0 was used to analyze the data. We used the t-test and analysis of variance to compare the differences in the Attentional Function Index scores to demographic and medical characteristics.
    Results
    The mean Attentional Function Index score was 59.53±1.69. There was a statistically significant difference between the scores in terms of current non-surgical treatment (P<0.000). Regarding the time elapsed after disease diagnosis, the difference between the Attentional Function Index scores was statistically significant (P<0.00).
    Conclusion
    Chemotherapy and hormone therapy can act as risk factors for cognitive impairment in patients with breast cancer.
    Keywords: Breast cancer, Attentional Function Index, Cognitive impairment, Perceived
  • Shahram Paydar, Saeedeh Pourahmad, Mohsen Azad, Shahram Bolandparvaz, Reza Taheri, Zahra Ghahramani, Ali Zamani, Marjan Jeddi, Fariba Karimi, Mohammad Hossein Dabbaghmanesh, Mesbah Shams, Hamid Reza Abbasi Pages 47-52
    Background
    Clinically frank thyroid nodules are common and believed to be present in 4% to 10% of the adult population in the United States. In the current literature, fine needle aspiration biopsies are considered to be the milestone of a model which helps the physician decide whether a certain thyroid nodule needs a surgical approach or not. A considerable fact is that sensitivity and specificity of the fine needle aspiration varies significantly as it remains highly dependent on the operator as well as the cytologist’s skills. Practically, in the above group of patients, thyroid lobectomy/isthmusectomy becomes mandatory for attaining a definitive diagnosis where the majority (70%-80%) have a benign surgical pathology. The scattered nature of clinically gathered data and analysis of their relevant variables need a compliant statistical method. The artificial neural network is a branch of artificial intelligence. We have hypothesized that conduction of an artificial neural network applied to certain clinical attributes could develop a malignancy risk assessment tool to help physicians interpret the fine needle aspiration biopsy results of thyroid nodules in a context composed of patient’s clinical variables, known as malignancy related risk factors.
    Methods
    We designed and trained an artificial neural network on a prospectively formed cohort gathered over a four year period (2007-2011). The study population comprised 345 subjects who underwent thyroid resection at Nemazee and Rajaee hospitals, tertiary care centers of Shiraz University of Medical Sciences, and Rajaee Hospital as a level I trauma center in Shiraz, Iran after having undergone thyroid fine needle aspiration. Histopathological results of the fine needle aspirations and surgical specimens were analyzed and compared by experienced, board-certified pathologists who lacked knowledge of the fine needle aspiration results for thyroid malignancy.
    Results
    We compared the preoperative fine needle aspiration and surgical histopathology results. The results matched in 63.5% of subjects. On the other hand, fine needle aspiration biopsy results falsely predicted malignant thyroid nodules in 16% of cases (false-negative). In 20.5% of subjects, fine needle aspiration was falsely positive for thyroid malignancy. The Resilient back Propagation (RP) training algorithm lead to acceptable accuracy in prediction for the designed artificial neural network (64.66%) by the cross- validation method. Under the cross-validation method, a back propagation algorithm that used the resilient back propagation protocol - the accuracy in prediction for the trained artificial neural network was 64.66%.
    Conclusion
    An extensive bio-statistically validated artificial neural network of certain clinical, paraclinical and individual given inputs (predictors) has the capability to stratify the malignancy risk of a thyroid nodule in order to individualize patient care. This risk assessment model (tool) can virtually minimize unnecessary diagnostic thyroid surgeries as well as FNA misleading.
    Keywords: Malignancy, Risk prediction model, Thyroid nodules, Artificial neural network
  • Heba G. El, Sheredy, Rabie Ramadan, Yasser Hamed Pages 53-62
    Background
    Breast cancer is the most frequent malignant tumor in women worldwide. In recent years, defined reconstruction principles along with numerous surgical techniques with volume replacement have been published. Autologous breast reconstruction is more natural but leaves donor site morbidity. It provides the opportunity to restore the breast mound without the need for scars. This study aims to evaluate the complications of radiotherapy after immediate breast reconstruction with implants in breast cancer patients who submitted to skin sparing mastectomy and nipple sparing mastectomy by taking into consideration the risk factors and management at our institution.
    Methods
    The current study prospectively included patients with invasive breast cancer admitted between January and June 2012 who were scheduled for skin sparing mastectomy or nipple sparing mastectomy and axillary dissection followed by immediate breast reconstruction with implant. Patients received adjuvant chemotherapy followed by conventional fractionated radiation. Complications were classified as either minor or major. The minor complications included capsular contracture (Baker 1-2), seroma, minor skin infection and skin dehiscence without exposure of the implant. Major complications included capsular contracture (Baker 3-4), severe infection and major wound dehiscence with implant exposure. Capsular contracture was scored according to the modified Baker classification.
    Results
    The study included 38 patients. Of these, 28 had skin sparing mastectomy while 10 underwent nipple sparing mastectomy. The overall complication rate was 71%. We observed minor complications in 18 patients while 9 patients had major complications. Complications occurred with a median time of 13 months following radiotherapy completion. All minor complications were managed conservatively whereas all major complications required repeat surgery. No loco-regional recurrences occurred during the follow up period.
    Conclusion
    We determined that age >40 years, smoking, diabetes, dose to prosthesis ≥45 Gy, and prosthetic volume exposed to the radiation dose of >75% were risk factors for the development of post-radiation complications in an immediately reconstructed breast with implant after skin sparing mastectomy and nipple sparing mastectomy. Adequate selection of patients to exclude those who have significant risk to develop complications will lower the complication rate, improve surgical techniques, allow better quality of implants, and limit tissue damage after radiotherapy.
    Keywords: Immediate reconstruction, Breast cancer, Adjuvant radiotherapy, Complications
  • Mahdi Shahriari, Gholamreza Fathpour, Fazl Saleh Pages 63-66
    Acute leukemias represent approximately 30% of malignant diseases in patients under the age of 15 years. Leukemic infiltration of the central nervous system and testis are common events, particularly as sites of relapse in the third year after diagnosis. Management of acute lymphoblastic leukemia is based on long-term chemotherapy, leading to a cure rate of approximately 80% of children and adolescents. Despite this elevated cure rate, approximately 20% have disease relapse. Bone marrow is the most frequent site of relapse followed by the central nervous system. Nevertheless, relapse can occur in any tissue or organ. Recurrence in the mucocutaneous area is extremely uncommon and rare in childhood acute lymphoblastic leukemia. To our knowledge, a few case reports (mostly in adolescents or adults) have been published regarding relapse in the mucosal area (oral cavity) and skin. Most patients had concomitant bone marrow relapse. In this paper we report a case of recurrence of T-cell acute lymphoblastic leukemia in the hard palate, lip and skin of a child without bone marrow relapse.
    Keywords: Leukemid, Leukemia cutis, Mucocutaneous involvement, T cell leukemia