Correlation between the incidence of PIK3CA mutations in breast cancer and histopathological characteristics of the tumor

Czech version

Authors: A. Mendelová ^1,2; E. Jezková ^1,2; P. Zubor ¹; V. Holubeková ²; Z. Lasabová ²; L. Plank ³; J. Danko ¹
Authors‘ workplace: Gynekologicko-pôrodnícka klinika JLF UK a UNM, Jesseniova lekárska fakulta, Martin, Univerzita Komenského, Bratislava, Slovenská republika, prednosta prof. MUDr. J. Danko, CSc. ¹; Ústav molekulovej biológie JLF UK a UNM, Jesseniova lekárska fakulta, Martin, Univerzita Komenského, Bratislava, Slovenská republika, prednosta doc. RNDr. Z. Lasabová, PhD. ²; Ústav patologickej anatómie JLF UK a UNM, Jesseniova lekárska fakulta, Martin, Univerzita Komenského, Bratislava, Slovenská republika, prednosta prof. MUDr. L. Plank, CSc. ³
Published in: Ceska Gynekol 2014; 79(4): 283-288

Overview

Objective:
To determine the presence of mutations in exon 9 (encoding the helical domain) and exon 20 (encoding the kinase domain) of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene in DNA obtained from paraffin embedded tissue from patients with carcinoma of the mammary gland and to correlate results with clinicopathological characteristics of cancer.

Design:
Prospective clinical study.

Setting:
Department of Molecular Biology, Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Commenius University, Martin, Slovak Republic.

Methods:
In set of 95 tissue samples from patients with breast cancer, mutations in exon 9 and 20 were analysed by sequencing. We also observed the associations between mutations and histopathological characteristics of tumor.

Results:
Overall, mutations were present in 25.3% (24/95) of PIK3CA gene, of this 14.7% (14/95) of mutations were located in exon 9 and 10.5% (10/95) of mutations were in exon 20. We detected three “hotspot” mutations, two were located in exon 9 (E542K, E545K) and the third mutation was found in exon 20 (H1047R). Mutations in exon 9 showed significant correlation with lower grade(p = 0.0074) and pN status without metastases(p = 0.0415). Mutations in exon 20 were associated with higher age of patient (p = 0.0249). The E545K mutation correlated with lower grade (p = 0.0013) and pN status (p = 0.0232) particularly; the H1047R mutation was significantly more frequent in lobular type of breast cancer (p = 0.0354).

Conclusion:
The PI3K signaling pathway plays a critical oncogenic role in the development of human breast cancer and the prevalence of its deregulation advocates its potential as a feasible therapeutic target. In our study we demonstrate a significant correlation between the presence of PIK3CA mutations and some clinicopathological characteristics of tumour. We have shown that the mutations in exon 9 of PIK3CA were associated with favourable prognostic factors.

Keywords:
“hotspot” mutation, PIK3CA, PI3K pathway, breast cancer

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