Cancer Res Treat.  2019 Oct;51(4):1518-1526. 10.4143/crt.2019.008.

Loss of LKB1 Protein Expression Correlates with Increased Risk of Recurrence and Death in Patients with Resected, Stage II or III Colon Cancer

• Sfakianaki M
• Papadaki C
• Tzardi M
• Trypaki M
• Alam S
• Lagoudaki
• Messaritakis I
• Zoras O
• Mavroudis
• Georgoulias V
• Souglakos

• KMID: 2460600
• DOI: http://doi.org/10.4143/crt.2019.008

Abstract

PURPOSE
The purpose of this study was to investigate the prognostic significance of liver kinase b1 (LKB1) loss in patients with operable colon cancer (CC).
MATERIALS AND METHODS
Two hundred sixty-two specimens from consecutive patients with stage III or high-risk stage II CC, who underwent surgical resection with curative intent and received adjuvant chemotherapy with fluoropyrimidine and oxaliplatin, were analyzed for LKB1 protein expression loss, by immunohistochemistry as well as for KRAS exon 2 and BRAF(V600E) mutations by Sanger sequencing and TS, ERCC1, MYC, and NEDD9 mRNA expression by real-time quantitative reverse transcription polymerase chain reaction.
RESULTS
LKB1 expression loss was observed in 117 patients (44.7%) patients and correlated with right-sided located primaries (p=0.032), and pericolic lymph nodes involvement (p=0.003), BRAF(V600E) mutations (p=0.024), and TS mRNA expression (p=0.041). Patients with LKB1 expression loss experienced significantly lower disease-free survival (DFS) (hazard ratio [HR], 1.287; 95% confidence interval [CI], 1.093 to 1.654; p=0.021) and overall survival (OS) (HR, 1.541; 95% CI, 1.197 to 1.932; p=0.002), compared to patients with LKB1 expressing expressing tumors. Multivariate analysis revealed LKB1 expression loss as independent prognostic factor for both decreased DFS (HR, 1.217; 95% CI, 1.074 to 1.812; p=0.034) and decreased OS (HR, 1.467; 95% CI, 1.226 to 2.122; p=0.019).
CONCLUSION
Loss of tumoral LKB1 protein expression, constitutes an adverse prognostic factor in patients with operable CC.

Keyword

LKB1; KRAS; BRAF; MSI; Prognosis; Stage II-III

MeSH Terms

Chemotherapy, Adjuvant
Colon*
Colonic Neoplasms*
Disease-Free Survival
Exons
Humans
Immunohistochemistry
Liver
Lymph Nodes
Multivariate Analysis
Phosphotransferases
Polymerase Chain Reaction
Prognosis
Recurrence*
Reverse Transcription
RNA, Messenger
Phosphotransferases
RNA, Messenger

Figure

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  Fig. 1. Disease-free survival according to LKB1 protein expression loss by immunohistochemistry. DFS, disease-free survival; HR, hazard ratio; CI, confidence interval.

• 

  Fig. 2. Overall survival according to LKB1 protein expression loss by immunohistochemistry. HR, hazard ratio; CI, confidence interval.

Reference

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