PMID- 26384210 OWN - NLM STAT- MEDLINE DCOM- 20160421 LR - 20181202 IS - 1465-542X (Electronic) IS - 1465-5411 (Print) IS - 1465-5411 (Linking) VI - 17 DP - 2015 Sep 17 TI - ALK alteration is a frequent event in aggressive breast cancers. PG - 127 LID - 10.1186/s13058-015-0610-3 [doi] LID - 127 AB - INTRODUCTION: Breast cancer is the most common female malignancy worldwide and, despite improvements in treatment modalities, there are increased chances of recurrence and metastasis in a substantial number of cases and it remains one of the major causes of mortality among female cancer patients. Anaplastic lymphoma kinase (ALK) gene has been found to be altered in several solid and hematologic tumors. We aimed to comprehensively study the prevalence of ALK expression, and changes in copy number and translocation in a large cohort of breast cancer cases in a Middle Eastern population. METHODS: ALK protein expression was investigated by immunohistochemistry and numerical and structural variations of the ALK gene were analyzed by fluorescence in situ hybridization (FISH) in a tissue microarray format in a cohort of more than 1000 Middle Eastern breast cancers. The data were correlated with clinicopathologic parameters and other important molecular biomarkers. RESULTS: Immunohistochemical analysis showed ALK overexpression in 36.0 % of the breast cancer patients and gene amplification was present in 13.3 % of cases, seen by FISH analyses. ALK overexpression was significantly associated with ALK gene amplification (p = 0.0031). ALK-overexpressing tumors showed significant association with high-grade tumors (p = 0.0039), ductal histologic subtype (p = 0.0076), triple-negative phenotype (p = 0.0034), and high Ki-67 (p = 0.0001) and p-AKT (p <0.0001). CONCLUSIONS: Immunohistochemical analysis showed ALK is overexpressed in a substantial proportion of breast cancers and possibly plays a significant role in the aggressive behavior of this cancer. Gene amplification is hypothesized to be a possible cause for a significant proportion of this overexpression. Based on these findings, a potential role for an ALK inhibitor, as a therapeutic agent targeting aggressive subtypes of breast cancer, merits further investigation. FAU - Siraj, Abdul K AU - Siraj AK AD - Department of Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Makkah Al Mukarramah Branch Road, Riyadh, 12713, Saudi Arabia. asiraj@kfshrc.edu.sa. FAU - Beg, Shaham AU - Beg S AD - Department of Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Makkah Al Mukarramah Branch Road, Riyadh, 12713, Saudi Arabia. bshaham@kfshrc.edu.sa. FAU - Jehan, Zeenath AU - Jehan Z AD - Department of Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Makkah Al Mukarramah Branch Road, Riyadh, 12713, Saudi Arabia. zjehan@kfshrc.edu.sa. FAU - Prabhakaran, Sarita AU - Prabhakaran S AD - Department of Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Makkah Al Mukarramah Branch Road, Riyadh, 12713, Saudi Arabia. sprabakaran@kfshrc.edu.sa. FAU - Ahmed, Maqbool AU - Ahmed M AD - Department of Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Makkah Al Mukarramah Branch Road, Riyadh, 12713, Saudi Arabia. amaqbool@kfshrc.edu.sa. FAU - R Hussain, Azhar AU - R Hussain A AD - Department of Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Makkah Al Mukarramah Branch Road, Riyadh, 12713, Saudi Arabia. arajabali@kfshrc.edu.sa. FAU - Al-Dayel, Fouad AU - Al-Dayel F AD - Department of Pathology, King Faisal Specialist Hospital and Research Center, Makkah Al Mukarramah Branch Road, Riyadh, 12713, Saudi Arabia. dayelf@kfshrc.edu.sa. FAU - Tulbah, Asma AU - Tulbah A AD - Department of Pathology, King Faisal Specialist Hospital and Research Center, Makkah Al Mukarramah Branch Road, Riyadh, 12713, Saudi Arabia. tulbah@kfshrc.edu.sa. FAU - Ajarim, Dahish AU - Ajarim D AD - Oncology Center, King Faisal Specialist Hospital and Research Center, Makkah Al Mukarramah Branch Road, Riyadh, 12713, Saudi Arabia. ajarim@kfshrc.edu.sa. FAU - Al-Kuraya, Khawla S AU - Al-Kuraya KS AD - Department of Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Makkah Al Mukarramah Branch Road, Riyadh, 12713, Saudi Arabia. kkuraya@kfshrc.edu.sa. AD - Department of Pathology, Al-Faisal University, Al Zahrawi Street, Riyadh, 11533, Saudi Arabia. kkuraya@kfshrc.edu.sa. LA - eng PT - Journal Article DEP - 20150917 PL - England TA - Breast Cancer Res JT - Breast cancer research : BCR JID - 100927353 RN - 0 (Biomarkers, Tumor) RN - 0 (Ki-67 Antigen) RN - EC 2.7.10.1 (ALK protein, human) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Adult MH - Anaplastic Lymphoma Kinase MH - Biomarkers, Tumor/genetics MH - Breast Neoplasms/*genetics MH - Cell Line, Tumor MH - Female MH - Gene Dosage/genetics MH - Humans MH - Immunohistochemistry/methods MH - In Situ Hybridization, Fluorescence/methods MH - Ki-67 Antigen/genetics MH - Middle Aged MH - Mutation/*genetics MH - Neoplasm Recurrence, Local/genetics MH - Receptor Protein-Tyrosine Kinases/*genetics PMC - PMC4588266 EDAT- 2015/09/19 06:00 MHDA- 2016/04/22 06:00 PMCR- 2015/09/17 CRDT- 2015/09/19 06:00 PHST- 2015/03/02 00:00 [received] PHST- 2015/07/07 00:00 [accepted] PHST- 2015/09/19 06:00 [entrez] PHST- 2015/09/19 06:00 [pubmed] PHST- 2016/04/22 06:00 [medline] PHST- 2015/09/17 00:00 [pmc-release] AID - 10.1186/s13058-015-0610-3 [pii] AID - 610 [pii] AID - 10.1186/s13058-015-0610-3 [doi] PST - epublish SO - Breast Cancer Res. 2015 Sep 17;17:127. doi: 10.1186/s13058-015-0610-3.