Related Experiment Video
Updated: Jun 25, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Molecular alterations of EGFR and PIK3CA in uterine serous carcinoma
Monica Prasad Hayes1, Wayne Douglas, Lora Hedrick Ellenson
1Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, USA. monica.prasad@mssm.edu
Objectives:
Uterine serous carcinoma (USC) is an aggressive endometrial cancer associated with poor prognosis despite comprehensive surgical staging and adjuvant chemotherapy and radiation therapy. Biologic targets have yet to be fully explored in this disease and research on such targets could lead to clinical trials utilizing a new class of therapeutics. This study sought to evaluate primary USC tumors for molecular alterations in epidermal growth factor receptor (EGFR) and the recently characterized oncogene PIK3CA, which encodes the catalytic p110-alpha subunit of phosphatidylinositol 3-kinase (PI3K) and thus activates the AKT-mTOR oncogenic pathway.
Methods:
Paraffin-embedded archival tissue of 45 primary USC tumors was utilized in this study. Immunohistochemical analysis of EGFR was performed and cases given a score of 0 to 12 calculated as the product of staining intensity (0 to 3+) and the percentage of positively stained cells (0-4), with 1=1-25%, 2=26-50%, 3=51-75%, and 4=76-100%. For mutational analysis, neoplastic tissue was microdissected and DNA was extracted with phenol-chloroform. Exons 18 through 21 of EGFR and exons 9 and 20 of PIK3CA, the most commonly mutated exons of these genes, were amplified and directly sequenced.
Results:
When EGFR was evaluated, moderate or strong EGFR membranous staining was observed in 25/45 (56%) USC cases. Thus, a mutational analysis was performed on 35 cases, including all cases with moderate and strong EGFR staining. No mutations were identified in EGFR. In contrast, PIK3CA mutations were confirmed in 5/34 (15%) of USC cases. Four cases were mutated in exon 20 and one case was mutated in exon 9.
Conclusions:
Since optimal treatment of uterine serous carcinoma remains unknown, novel therapeutic approaches need to be actively pursued. In the current study of primary USC tumors, oncogenic mutations of the PIK3CA gene were seen in 15% of USC cases. This represents the first report of this gene mutation in USC. In addition, EGFR stained positively in the majority of cases, suggesting a possible target protein. These findings warrant further investigation and suggest a potential role for therapeutic agents targeting the PI3K-AKT-mTOR pathway, such as rapamycin, as well as possible targets of EGFR in the treatment of uterine serous carcinoma.
Insights
Overt PIK3CA gene mutations were found in 15% of uterine serous carcinoma (USC) cases, suggesting a potential therapeutic target. Epidermal growth factor receptor (EGFR) was also identified as a possible target in this aggressive cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Uterine serous carcinoma (USC) is an aggressive endometrial cancer with a poor prognosis.
- Current treatments including surgery, chemotherapy, and radiation therapy have limited efficacy.
- Novel therapeutic targets are needed for improved patient outcomes.
Purpose of the Study:
- To investigate molecular alterations in epidermal growth factor receptor (EGFR) and PIK3CA in primary USC tumors.
- To identify potential therapeutic targets for USC treatment.
Main Methods:
- Archival tissue from 45 primary USC tumors was analyzed.
- Immunohistochemical analysis was performed for EGFR expression.
- Exons 18-21 of EGFR and exons 9 and 20 of PIK3CA were sequenced for mutations.
Main Results:
- EGFR membranous staining was observed in 56% of USC cases.
- No mutations were detected in the analyzed EGFR exons.
- PIK3CA mutations were identified in 15% of USC cases (5/34), with mutations in exon 20 (4 cases) and exon 9 (1 case).
Conclusions:
- PIK3CA mutations represent a potential therapeutic target in 15% of USC cases.
- EGFR overexpression suggests it may also be a target for novel therapies.
- These findings support further investigation into targeting the PI3K-AKT-mTOR pathway and EGFR in USC treatment.
