IMMUNOHISTOCHEMICAL EXPRESSION OF THE PROMISING THERAPEUTIC TARGET (HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2/NEU) IN IRAQI PATIENTS WITH MEDULLOBLASTOMA
DOI:
https://doi.org/10.22159/ajpcr.2018.v11i12.28373Keywords:
Medulloblastoma, Human epidermal growth factor receptor 2NEU, ImmunohistochemistryAbstract
Objectives: With the advent of ongoing novel modalities toward the treatment of human epidermal growth factor receptor 2 (HER2)/NEU - positive malignancies, the serious side effects of chemoradiotherapy have been minimized. Hence, this study was conducted to identify the patterns of immunohistochemical expression of the promising therapeutic target (HER2/NEU) among Iraqi patients with medulloblastoma in an attempt to provide basic histological information's that would help in future clinical researches.
Materials and Methods: In this retrospective study, 42 formalin - fixed paraffin - embedded tissue blocks represent cases of surgically removed medulloblastomas were retrieved from the archived materials in a specialized surgical hospital at Bagdad. The histological diagnosis had been revised, and all cases were stained by the immunohistochemical technique with HER2/NEU antibody and assessed independently by three pathologists.
Results: Out of 42 cases, only two which represent 4.76% showed positive results manifested by a strong membranous staining when immunohistochemically evaluated using the same scoring system established for HER2/NEU in breast cancer. 14 cases (33.3%) showed incomplete membranous and five cases (11.9%) showed only cytoplasmic reaction patterns.
Conclusion: The rate of expression of HER2/NEU in medulloblastoma among Iraqi patients is very low and found only in aggressive anaplastic histological type when immunohistochemically evaluated using the same scoring system established for HER2/NEU in breast cancer. However, a good number of negative cases showed cytoplasmic and incomplete membranous staining patterns highlighting the importance of establishing medulloblastoma - specific HER2/NEU scoring criteria and testing methods to discover the unique feature of expression of this therapeutic target in medulloblastoma.
Â
Downloads
References
Roussel MF, Hatten ME. Cerebellum development and medulloblastoma. Curr Top Dev Biol 2011;94:235-82.
Kumar V, Kumar V, McGuire T, Coulter DW, Sharp JG, Mahato RI, et al. Challenges and recent advances in medulloblastoma therapy. Trends Pharmacol Sci 2017;38:1061-84.
Gilbertson RJ. Medulloblastoma: Signalling a change in treatment. Lancet Oncol 2004;5:209-18.
Northcott PA, Jones DT, Kool M, Robinson GW, Gilbertson RJ, Cho YJ, et al. Medulloblastomics: The end of the beginning. Nat Rev Cancer 2012;12:818-34.
Kijima N, Kanemura Y. Molecular classification of medulloblastoma. Neurol Med Chir (Tokyo) 2016;56:687-97.
Massimino M, Antonelli M, Gandola L, Miceli R, Pollo B, Biassoni V, et al. Histological variants of medulloblastoma are the most powerful clinical prognostic indicators. Pediatr Blood Cancer 2013;60:210-6.
Kool M, Korshunov A, Remke M, Jones DT, Schlanstein M, Northcott PA, et al. Molecular subgroups of medulloblastoma: An international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, group 3, and group 4 medulloblastomas. Acta Neuropathol 2012;123:473-84.
Silva Rd, Marie SK, Uno M, Matushita H, Wakamatsu A, Rosemberg S, et al. CTNNB1, AXIN1 and APC expression analysis of different medulloblastoma variants. Clinics (Sao Paulo) 2013;68:167-72.
Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, et al. Molecular subgroups of medulloblastoma: The current consensus. Acta Neuropathol 2012;123:465-72.
Vinod K, Virender K, Timothy M, Donald W, Coulter JG, Ram IM. challenges and recent advances in medulloblastoma. Ther Trends Pharm Sci 2013;8:1061-84.
Buza N, Roque DM, Santin AD. HER2/neu in endometrial cancer: A Promising therapeutic target with diagnostic challenges. Arch Pathol Lab Med 2014;138:343-50.
Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: Planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 2014;32:3744-52.
Gilbertson RJ, Pearson AD, Perry RH, Jaros E, Kelly PJ. Prognostic significance of the c-erbB-2 oncogene product in childhood medulloblastoma. Br J Cancer 1995;71:473-7.
Gilbertson RJ. ERBB2 in pediatric cancer: Innocent until proven guilty. Oncologist 2005;10:508-17.
Holla SN, Nayak V, Bairy KL, Tripathy A, Holla S. Her-2 gene, receptors and drug target: A systematic review. Int J Pharm Pharm Sci 2016;8:4-9.
Ahmed N, Ratnayake M, Savoldo B, Perlaky L, Dotti G, Wels WS, et al. Regression of experimental medulloblastoma following transfer of HER2-specific T cells. Cancer Res 2007;67:5957-64.
Gupta M, Dahiya J, Marwaha RK, Dureja H. Therapies in cancer treatment: AN overview. Int J Pharm Pharm Sci 2015;4:1-9.
Mates M, Fletcher GG, Freedman OC, Eisen A, Gandhi S, Trudeau ME, et al. Systemic targeted therapy for her2-positive early female breast cancer: A systematic review of the evidence for the 2014 cancer care ontario systemic therapy guideline. Curr Oncol 2015;22:S114-22.
Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2016;17:367-77.
Kumar LP, Deepa SF, Moinca I, Suresh P, Naidu KV. Medulloblastoma: A common pediatric tumor: Prognostic factors and predictors of outcome. Asian J Neurosurg 2015;10:50.
Curran EK, Sainani KL, Le GM, Propp JM, Fisher PG. Gender affects survival for medulloblastoma only in older children and adults: A study from the surveillance epidemiology and end results registry. Pediatr Blood Cancer 2009;52:60-4.
Herms JW, Behnke J, Bergmann M, Christen HJ, Kolb R, Wilkening M, et al. Potential prognostic value of C-erbB-2 expression in medulloblastomas in very young children. J Pediatr Hematol Oncol 1997;19:510-5.
Nam DH, Wang KC, Kim YM, Chi JG, Kim SK, Cho BK. The effect of chromosome 17q presence, proliferative and apoptotic indices, expression of C-erbB-2, bcl-2 and p53 proteins on the prognosis of medulloblastoma. J Korean Med Sci 2000;15:452-6.
Meurer RT, Martins DT, Hilbig A, Ribeiro Mde C, Roehe AV, Barbosa-Coutinho LM, et al. Immunohistochemical expression of markers ki-67, neun, synaptophysin, p53 and HER2 in medulloblastoma and its correlation with clinicopathological parameters. Arq Neuropsiquiatr 2008;66:385-90.
Hofmann M, Stoss O, Shi D, Büttner R, van de Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: Results from a validation study. Histopathology 2008;52:797-805.
Perez EA, Press MF, Dueck AC, Jenkins RB, Kim C, Chen B, et al. Immunohistochemistry and fluorescence in situ hybridization assessment of HER2 in clinical trials of adjuvant therapy for breast cancer (NCCTG N9831, BCIRG 006, and BCIRG 005). Breast Cancer Res Treat 2013;138:99-108.
Cottu PH, Asselah J, Lae M, Pierga JY, Diéras V, Mignot L, et al. Intratumoral heterogeneity of HER2/neu expression and its consequences for the management of advanced breast cancer. Ann Oncol 2008;19:595-7.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
