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Comparative Study
. 2015 Aug;112(2):188-94.
doi: 10.1002/jso.23993. Epub 2015 Aug 7.

Alteration in PI3K/mTOR, MAPK pathways and Her2 expression/amplification is more frequent in uterine serous carcinoma than ovarian serous carcinoma

Haider Mahdi  1 , Joanne Xiu  2 , Sandeep K Reddy  2 , Robert DeBernardo  1
Affiliations
Comparative Study

Alteration in PI3K/mTOR, MAPK pathways and Her2 expression/amplification is more frequent in uterine serous carcinoma than ovarian serous carcinoma

Haider Mahdi et al. J Surg Oncol. 2015 Aug.

Abstract

Objectives: To compare the molecular profile of a large cohort of uterine papillary serous carcinoma (UPSC) and ovarian serous carcinoma (EOC-S).

Methods: 628 UPSC and 5335 EOC-S tumors were evaluated using a commercial multiplatform profiling service (CARIS Life Sciences, Phoenix, AZ). Specific testing performed included a combination of gene sequencing (Sanger, next generation sequencing), protein expression (IHC) and gene amplification (CISH or FISH).

Results: TP53 was the most commonly mutated gene in both UPSC and EOC-S (76% vs. 69%, P = 0.03). UPSC were more likely to have mutation in PIK3CA (29% vs. 2%, P < 0.001), FBXW7 (12% vs. 1%, P < 0.001), KRAS (9% vs. 5%, P < 0.001) PTEN (7% vs. 1%, P < 0.001), and CTNNB1 (2% vs. 0%, P < 0.001) compared to EOC-S. On the other hand, EOC-S were more likely to harbor mutation in BRCA1 (20% vs. 9% P = 0.17) and BRCA2 (18% vs. 6% P = 0.09). HER2 gene amplification (17% vs. 4%, P < 0.001) and Her2/neu expression (10% vs. 2%, P < 0.001) were more frequent in UPSC than EOC-S, respectively.

Conclusion: UPSC have a distinct mutation profile indicating higher activity of PI3K/AKT/mTOR, and MAPK pathways and Her2 expression/amplification but a trend toward lower frequency of alteration in homologous recombination pathway compared to EOC-S. Targeted PI3K/AKT/mTOR inhibitors should be evaluated in UPSC.

Keywords: BRCA; CARIS; HER2/neu; PI3K/AKT/mTOR; molecular profile; serous ovarian carcinoma; uterine papillary serous carcinoma.

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