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. 2016 Apr;7(2):158-65.
doi: 10.3978/j.issn.2078-6891.2015.067.

AKT expression is associated with degree of pathologic response in adenocarcinoma of the esophagus treated with neoadjuvant therapy

Nadia Saeed  1 , Ravi Shridhar  1 , Sarah Hoffe  1 , Khaldoun Almhanna  1 , Kenneth L Meredith  1
Affiliations

AKT expression is associated with degree of pathologic response in adenocarcinoma of the esophagus treated with neoadjuvant therapy

Nadia Saeed et al. J Gastrointest Oncol. 2016 Apr.

Abstract

Background: Neoadjuvant chemoradiation (NCRT) has become standard in the treatment of locally advanced esophageal adenocarcinoma (EAC) with survival correlated to degree of pathologic response. The phosphatidyl inositol 3 kinase (PI3K)/protein kinase B (AKT)/mTOR pathway plays an important role in tumorgenesis and resistance. We sought to elucidate the role of this pathway in patients with EAC who received NCRT.

Methods: After IRB approval, a prospective trial was initiated in which patients with EAC underwent endoscopic biopsies of normal and tumor tissue prior to instituting NCRT. Patients then proceeded to esophagectomy. The pre-treatment tissues underwent gene expression profiling. SAM method was used to analyze expression of AKT within normal and tumor tissue. Expression was then correlated to degree of pathologic response.

Results: One-hundred patients were consented for the study, of which 67 met final eligibility. Nineteen patient's tumors ultimately underwent gene expression profiling via microarray. The differential expression of all AKT isoforms in tumor tissue was markedly overexpressed compared to normal tissue (P=6×10(-5)). There were 3 patients designated as pNR, 6 as pPR, and 10 as pCR. Partial and non-responders had higher expressions of AKT compared to pCR with the non-responders consistently illustrated the highest expression of AKT (P=0.02). There was a significant correlation between individual isoforms of AKT-1, AKT-2, and AKT-3 and degree of pathologic response (P=0.002, 0.04, and 0.04 respectively).

Conclusions: AKT is overexpressed in patients with AC of the esophagus. Moreover, pathologic response to NCRT may be correlated with degree of AKT expression. Additional data is needed to clarify this relationship to potentially add targeted therapies to the neoadjuvant regimen.

Keywords: AKT expression; esophageal cancer; esophagectomy; neoadjuvant therapy; postoperative outcomes.

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Heat map of all AKT probesets (P=3×10−4).
Figure 2
Figure 2
(A) AKT expression in normal vs. tumor tissues for all isoforms. AKT is overexpressed in tumor tissues (mean diff. =−3.84; P=6×10−5); (B) AKT-1 expression (mean diff. =0.53; P=0.0074); (C) AKT-2 expression (mean diff. =−0.27; P=0.0025); (D) AKT-3 expression (mean diff. =1.07; P=0.0072).
Figure 3
Figure 3
(A) AKT all isoforms expression correlated to pathologic response to NCRT (mean diff. =−3.35 for pCR vs. pPR/pNR P=0.02); (B) correlation between AKT-1 expression and pathologic response to NCRT (mean diff. =0.39; P=0.002); (C) correlation between AKT-2 expression and pathologic response to NCRT (mean diff. =0.32, P=0.04); (D) correlation between AKT-3 expression and pathologic response to NCRT (mean diff. =0.58, P=0.04). NCRT, neoadjuvant chemoradiation; pCR, pathologic complete response; pPR, partial pathologic response; pNR, pathologic non-response.
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