摘要
<strong>Objective</strong><span style="font-family:Verdana;"><strong>:</strong></span><span style="font-family:""> <i><span style="font-family:Verdana;">PIK</span></i><span><span style="font-family:Verdana;">3</span><i><span style="font-family:Verdana;">CA</span></i></span><span style="font-family:Verdana;"> is the most common pathway affected by mutations in breast cancer. </span><i><span style="font-family:Verdana;">PIK</span></i><span><span style="font-family:Verdana;">3</span><i><span style="font-family:Verdana;">CA</span></i></span><span style="font-family:Verdana;">/PTEN pathway is under intense investigation as a possible target for molecular therapy. Dysregulation </span><i><span style="font-family:Verdana;">PIK</span></i><span><span style="font-family:Verdana;">3</span><i><span style="font-family:Verdana;">CA</span></i></span><span style="font-family:Verdana;">/PTEN pathway is a substantial mechanism for the development of resistance to anti-HER2 therapy. Therefore, we aimed to study the </span><i><span style="font-family:Verdana;">PIK</span></i><span><span style="font-family:Verdana;">3</span><i><span style="font-family:Verdana;">CA</span></i></span><span style="font-family:Verdana;">/PTEN in breast cancer patients in </span><span style="font-family:Verdana;">Saudi</span><span style="font-family:Verdana;"> population. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> We applied PTEN immunohistochemistry on 98 patients. Then, we applied next-generation sequencing to determine the genetic variations associated with the development of breast cancer and their correlations with clinicopathological variables. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">PTEN expression was significantly correlated with lymph node metastasis (LNM), tumor stage, lymphovascular invasion (LVI) </span><span style="font-family:Verdana;">and</span> <span style="font-family:Verdana;">triple negative</span><span style="font-family:Verdana;"> breast cancer (TNBC). The prevalence of the </span><i><span style="font-family:Verdana;">PIK</span></i><span><span style="font-family:Verdana;">3</span><i><span style="font-family:Verdana;">CA</span></i></span><span style="font-family:Verdana;"> mutation was 33.3% of cases and it was significantly associated with LNM, tumor stage, and with PTEN expression. </span><i><span style="font-family:Verdana;">c-MET</span> </i><span style="font-family:Verdana;">mutation was identified in 41.7% of cases and it was associated with tumor stage and with TNBC, while </span><i><span style="font-family:Verdana;">c-KIT </span></i><span style="font-family:Verdana;">mutation</span><i> </i><span style="font-family:Verdana;">was detected in 20.8% of cases, and it was significantly associated with TNBC only. Patients with positive PTEN expression had a significantly better overall survival (OS);on the contrary, patients with </span><i><span style="font-family:Verdana;">PIK</span></i><span><span style="font-family:Verdana;">3</span><i><span style="font-family:Verdana;">CA</span></i></span><span style="font-family:Verdana;"> and</span><i><span style="font-family:Verdana;"> c-MET </span></i><span style="font-family:Verdana;">had a significantly worse OS. </span><b><span><span style="font-family:Verdana;">Conclusion:</span><i> </i></span></b><span style="font-family:Verdana;">Our study confirms the importance of </span><i><span style="font-family:Verdana;">PIK3CA/PTEN</span></i><span style="font-family:Verdana;"> pathway in breast cancer patients. A high frequency of </span><i><span style="font-family:Verdana;">PIK</span></i><span><span style="font-family:Verdana;">3</span><i><span style="font-family:Verdana;">CA</span></i></span><span style="font-family:Verdana;"> and </span><i><span style="font-family:Verdana;">c-MET</span></i><span style="font-family:Verdana;"> mutations w</span></span><span style="font-family:Verdana;">as</span><span style="font-family:Verdana;"> detected and w</span><span style="font-family:Verdana;">as</span><span style="font-family:""><span style="font-family:Verdana;"> associated with </span><span style="font-family:Verdana;">poor</span><span style="font-family:Verdana;"> prognosis. Both </span><i><span style="font-family:Verdana;">c-MET </span></i><span style="font-family:Verdana;">and </span><i><span style="font-family:Verdana;">c-KIT</span></i><span style="font-family:Verdana;"> genes have significant roles in developing TNBC. These findings should be expanded to a larger group study to improve the clinical outcomes and individualizing treatment.</span></span>
<strong>Objective</strong><span style="font-family:Verdana;"><strong>:</strong></span><span style="font-family:""> <i><span style="font-family:Verdana;">PIK</span></i><span><span style="font-family:Verdana;">3</span><i><span style="font-family:Verdana;">CA</span></i></span><span style="font-family:Verdana;"> is the most common pathway affected by mutations in breast cancer. </span><i><span style="font-family:Verdana;">PIK</span></i><span><span style="font-family:Verdana;">3</span><i><span style="font-family:Verdana;">CA</span></i></span><span style="font-family:Verdana;">/PTEN pathway is under intense investigation as a possible target for molecular therapy. Dysregulation </span><i><span style="font-family:Verdana;">PIK</span></i><span><span style="font-family:Verdana;">3</span><i><span style="font-family:Verdana;">CA</span></i></span><span style="font-family:Verdana;">/PTEN pathway is a substantial mechanism for the development of resistance to anti-HER2 therapy. Therefore, we aimed to study the </span><i><span style="font-family:Verdana;">PIK</span></i><span><span style="font-family:Verdana;">3</span><i><span style="font-family:Verdana;">CA</span></i></span><span style="font-family:Verdana;">/PTEN in breast cancer patients in </span><span style="font-family:Verdana;">Saudi</span><span style="font-family:Verdana;"> population. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> We applied PTEN immunohistochemistry on 98 patients. Then, we applied next-generation sequencing to determine the genetic variations associated with the development of breast cancer and their correlations with clinicopathological variables. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">PTEN expression was significantly correlated with lymph node metastasis (LNM), tumor stage, lymphovascular invasion (LVI) </span><span style="font-family:Verdana;">and</span> <span style="font-family:Verdana;">triple negative</span><span style="font-family:Verdana;"> breast cancer (TNBC). The prevalence of the </span><i><span style="font-family:Verdana;">PIK</span></i><span><span style="font-family:Verdana;">3</span><i><span style="font-family:Verdana;">CA</span></i></span><span style="font-family:Verdana;"> mutation was 33.3% of cases and it was significantly associated with LNM, tumor stage, and with PTEN expression. </span><i><span style="font-family:Verdana;">c-MET</span> </i><span style="font-family:Verdana;">mutation was identified in 41.7% of cases and it was associated with tumor stage and with TNBC, while </span><i><span style="font-family:Verdana;">c-KIT </span></i><span style="font-family:Verdana;">mutation</span><i> </i><span style="font-family:Verdana;">was detected in 20.8% of cases, and it was significantly associated with TNBC only. Patients with positive PTEN expression had a significantly better overall survival (OS);on the contrary, patients with </span><i><span style="font-family:Verdana;">PIK</span></i><span><span style="font-family:Verdana;">3</span><i><span style="font-family:Verdana;">CA</span></i></span><span style="font-family:Verdana;"> and</span><i><span style="font-family:Verdana;"> c-MET </span></i><span style="font-family:Verdana;">had a significantly worse OS. </span><b><span><span style="font-family:Verdana;">Conclusion:</span><i> </i></span></b><span style="font-family:Verdana;">Our study confirms the importance of </span><i><span style="font-family:Verdana;">PIK3CA/PTEN</span></i><span style="font-family:Verdana;"> pathway in breast cancer patients. A high frequency of </span><i><span style="font-family:Verdana;">PIK</span></i><span><span style="font-family:Verdana;">3</span><i><span style="font-family:Verdana;">CA</span></i></span><span style="font-family:Verdana;"> and </span><i><span style="font-family:Verdana;">c-MET</span></i><span style="font-family:Verdana;"> mutations w</span></span><span style="font-family:Verdana;">as</span><span style="font-family:Verdana;"> detected and w</span><span style="font-family:Verdana;">as</span><span style="font-family:""><span style="font-family:Verdana;"> associated with </span><span style="font-family:Verdana;">poor</span><span style="font-family:Verdana;"> prognosis. Both </span><i><span style="font-family:Verdana;">c-MET </span></i><span style="font-family:Verdana;">and </span><i><span style="font-family:Verdana;">c-KIT</span></i><span style="font-family:Verdana;"> genes have significant roles in developing TNBC. These findings should be expanded to a larger group study to improve the clinical outcomes and individualizing treatment.</span></span>
作者
Rami Nassir
Ghada Esheba
Hanan M. Abd Elmoneim
Ahlam S. Altowairqi
Ghassan Nouman
Rami Nassir;Ghada Esheba;Hanan M. Abd Elmoneim;Ahlam S. Altowairqi;Ghassan Nouman(Department of Pathology, School of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia;Department of Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt;Department of Pathology, Faculty of Medicine, Minia University, Minia, Egypt;Faculty of Nursing, Umm Al-Qura University, Makkah, Saudi Arabia)
