Alteration in PI3K/mTOR, MAPK pathways and Her2 expression/amplification is more frequent in uterine serous carcinoma than ovarian serous carcinoma. Issue 2 (7th August 2015)

• Record Type: Journal Article
• Authors: Mahdi, Haider; Xiu, Joanne; Reddy, Sandeep K.; DeBernardo, Robert
• Is Part Of: Journal of surgical oncology. Volume 112:Issue 2(2015:Aug. 01)
• Page Start: 188
• Page End: 194
• Publication Date: 2015-08-07
• Subjects: Cancer -- Surgery -- Periodicals; Neoplasms -- Periodicals; 616
• DOI: 10.1002/jso.23993
• Languages: English
• ISSNs: 0022-4790

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="jso23993-sec-0001" sec-type="section"> <title>Objectives</title> <p>To compare the molecular profile of a large cohort of uterine papillary serous carcinoma (UPSC) and ovarian serous carcinoma (EOC‐S).</p> </sec> <sec id="jso23993-sec-0002" sec-type="section"> <title>Methods</title> <p>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).</p> </sec> <sec id="jso23993-sec-0003" sec-type="section"> <title>Results</title> <p>TP53 was the most commonly mutated gene in both UPSC and EOC‐S (76% vs. 69%, <italic>P</italic> = 0.03). UPSC were more likely to have mutation in PIK3CA (29% vs. 2%, <italic>P</italic> < 0.001), FBXW7 (12% vs. 1%, <italic>P</italic> < 0.001), KRAS (9% vs. 5%, <italic>P</italic> < 0.001) PTEN (7% vs. 1%, <italic>P</italic> < 0.001), and CTNNB1 (2% vs. 0%, <italic>P</italic> < 0.001) compared to EOC‐S. On the other hand, EOC‐S were more likely to harbor mutation in BRCA1 (20% vs. 9% <italic>P</italic> = 0.17) and BRCA2 (18% vs. 6% <italic>P</italic> = 0.09). HER2 gene amplification (17% vs. 4%, <italic>P</italic> < 0.001) and Her2/neu expression (10% vs. 2%, <italic>P</italic> < 0.001) were more frequent in UPSC than EOC‐S, respectively.</p> </sec> <sec id="jso23993-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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. <italic>J. Surg. Oncol. 2015 111:188–194</italic>. © 2015 Wiley Periodicals, Inc.</p> </sec> </abstract>