Journal of Pathology and Translational Medicine

Original Articles

Prognostic role of ALK-1 and h-TERT expression in glioblastoma multiforme: correlation with ALK gene alterations: Dalia Elsers, Doaa F. Temerik, Alia M. Attia, A. Hadia, Marwa T. Hussien; J Pathol Transl Med. 2021;55(3):212-224. Published online May 11, 2021; DOI: https://doi.org/10.4132/jptm.2021.03.15

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Background
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is expressed in the developing central and peripheral nervous systems during embryogenesis. Human telomerase reverse transcriptase (h-TERT) protein resumption is the main process of preservation of telomeres that maintains DNA integrity. The present study aims to evaluate the prognostic role of ALK-1 and h-TERT protein expression and their correlation with ALK gene alterations in glioblastoma multiforme (GBM).
Methods
The current study is a retrospective study on a cohort of patients with GBM (n = 53) that attempted to detect ALK gene alterations using fluorescence in situ hybridization. ALK-1 and h-TERT proteins were evaluated using immunohistochemistry.
Results
Score 3 ALK-1 expression was significantly associated with male sex, tumor multiplicity, Ki labeling index (Ki LI), and type of therapeutic modality. Score 3 h-TERT expression exhibited a significant association with Ki LI. ALK gene amplifications (ALK-A) were significantly associated with increased Ki LI and therapeutic modalities. Score 3 ALK-1 protein expression, score 3 h-TERT protein expression, and ALK-A were associated with poor overall survival (OS) and progression-free survival (PFS). Multivariate analysis for OS revealed that ALK gene alterations were an independent prognostic factor for OS and PFS.
Conclusions
High protein expression of both ALK-1 and h-TERT, as well as ALK-A had a poor impact on the prognosis of GBM. Further studies are needed to establish the underlying mechanisms.

Citations

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Association of human telomerase reverse transcriptase promoter mutation with unfavorable prognosis in glioma: A systematic review and meta-analysis
Rongxuan Hua, Qiuxuan Li, Han Gao, Boya Wang, Chengwei He, Ying Wang, Sitian Zhang, Lei Gao, Hongwei Shang, Wen Wang, Jingdong Xu
Journal of Research in Medical Sciences.2023; 28(1): 47. CrossRef
Immunohistochemical surrogates for molecular alterations for the classification and grading of gliomas
Viharkumar Patel, Sanda Alexandrescu
Seminars in Diagnostic Pathology.2022; 39(1): 78. CrossRef
Meme Kanseri Hastalarında hTERT Gen Ekspresyonunun Klinikopatolojik Önemi
Ebubekir DİRİCAN, Burak KANKAYA, Zeynep TATAR
Sağlık Bilimlerinde Değer.2022; 12(1): 22. CrossRef
Prognostic and predictive markers in glioblastoma and ALK overexpression
Jang-Hee Kim
Journal of Pathology and Translational Medicine.2021; 55(3): 236. CrossRef

Angiogenensis and Overexpression of p53 Gene Produc in Brain Tumor.: Jeong Yun Shim, Ho Guen Kim, Tai Seung Kim; Korean J Pathol. 1997;31(1):23-33.

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Abstract PDF: Angiogenesis depends on the net balance between positive and negative angiogenic factors. Tumor cells are angiogenic resulting from increased production of positive factors and decreased production of negative factors. Among these, vascular endothelial growth factor and glioma- derived angiogenesis inhibiting factor are related to glioblastoma multiforme. The p53 gene is more frequently mutated than any other known oncogene or tumor suppressor gene in human tumors including glioblastoma multiforme. Angiogenesis is reported to be controlled by p53 regulation in recent studies. To examine the effect of p53 overexpression on angiogenesis in glioblastoma multiforme, we performed immunohistochemical staining in 51 cases of glioblastoma multiforme, using monoclonal antibodies to p53 protein and factor VIII. 20 cases of low grade astrocytoma were used as control. p53 overexpression was present in 15(75%) of 20 cases of low grade astrocytoma and the mean vessel count was 37.7+/-9.9 at x200 field and 17.5+/-5.8 at x400 field. p53 overexpression was present in 35(68%) of 51 cases of glioblastoma multiforme and the mean vessel count was 91.9 45.8 at x200 field and 40.7 19.1 at x400 field. Mean vessel count in low grade astrocytoma with p53 overexpression was 39.4 10.2 at x200 field and 18.9 5.7 at x400 field, while in cases without p53 overexpression it was 32.4+/-7.6 at x200 field and 13.2 3.5 at x400 field. Mean vessel count in glioblastoma multiforme with p53 overexpression was 94.5+/-51.8 at x200 field and 42.1+/-16.8 at x400 field, while in cases without p53 overexpression it was 86.1+/-29.5 at x200 field and 37.1+/-16.8 at x400 field. The mean survival time was 12.4 months in the 39 cases of glioblastoma multiforme in which follow-up studies were possible. Significant prognostic factors were age, p53 overexpression and adjuvant therapy. These results show that p53 gene mutation is one of the many contributing factors to angiogenesis in glioblastoma multiforme. In addition, other oncogenes and tumor suppressor genes, as well as growth factors may be involved. Age, p53 overexpression and adjuvant therapy proved to be significant prognostic factors, while microvessel density was not.

Overexpression of Mutant p53 in Human Anaplastic Astrocytoma and Glioblastoma Multiforme.: Sang Sook Lee, Kam Rae Cho, Cheoul Hee Yun, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang, Eun Ik Sohn; Korean J Pathol. 1994;28(4):376-380.

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Abstract PDF: A total of 30 cases of cerebral gliomas, including 6 cases of low grade astrocytomas, 6 anaplasticastrocytoomas and l8 glioblastomas multiforme, was examined immunohistochemically to demonstrate the overexpression of mutant forms of p53 protein and to evaluate their relationships with histological subtypes. A p53 monoclonal antibody was applied to the routine formalin fixed, paraffin-embedded tissues for this study using microwave-assisted avidin-biotin method. Overexpression of p53 protein was identified in 4 out of 6 anaplastic astrocytomas (66.7%) and in l3 out of l8 glioblastomas multiforme (72.2%). No immunohistochemical positivity of p53 was found in adjacent normal brain tissue, gliosis and 6 cases of astrocytoma. These results suggest that overexpression of mutant p53 may be an important step in the development and progression of malignant astrocytoma, especially of the aggressive subtypes of glioma, including glioblastoma multiforme.

Histologic Grading of Astrocytic Neoplasms in Conjunction with Evaluation of Proliferative Activity Using Ag-NORs Count PCNA Expression, and Flow CYtometric DNA Analysis.: Mee Yon Cho, Soon Hee Jung, Tal Seung Kim, Yong Pyo Han; Korean J Pathol. 1994;28(1):49-55.

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Abstract PDF: Although the histologic grade of astrocytic neoplasms of the brain have been used as a prognostic factor, the lack of an objective criteria is possible to create the disagreement of classification. We evaluated 25 cases of astrocytic neoplasms of brain to document the usefulness of prolifera-tive potential of tumor as a prognostic indicator and the correlation with histologic grade by Nils Ringertz. The Ringertz's classification was relatively simple in an application among the variable systems and easy to define the differentiate from grade to grade. The examined cases were com-prised of 7 astrocytomas, 9 anaplastic astrocytomas and 9 glioblastoma multif6rmes. The prolife-rative potential of tumors were measured by Ag-NORs count, PCNA labeling index and flow cytometric analysis. The mean numbers of Ag-NORs per cell and PCNA labeling index were sig-nificantly differ among each histologic grade. In addition, abnormal DNA content and high prolif-erative index were frequently identified in anaplastic astrocytoma and glioblastoma multiforme. Therefore, the Ag-NORs counts, PCNA labeling index, DNA index and proliferative index were well correlated with the histologic grade.

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