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

Cancer Research and Treatment 2019년 51권 4호 p.1518 ~ 1526
 ( Sfakianaki Maria ) - University of Crete School of Medicine Laboratory of Translational Oncology

 ( Papadaki Chara ) - University of Crete School of Medicine Laboratory of Translational Oncology
 ( Tzardi Maria ) - University General Hospital of Heraklion Department of Pathology
 ( Trypaki Maria ) - University of Crete School of Medicine Laboratory of Translational Oncology
 ( Alam Sardar ) - University of Crete School of Medicine Laboratory of Translational Oncology
 ( Lagoudaki Eleni D. ) - University of Crete School of Medicine Laboratory of Translational Oncology
 ( Messaritakis Ippokratis ) - University of Crete School of Medicine Laboratory of Translational Oncology
 ( Zoras Odysseas ) - University General Hospital of Heraklion Department of Surgical Oncology
 ( Mavroudis Dimitris ) - University General Hospital of Heraklion Department of Medical Oncology
 ( Georgoulias Vassilis ) - University of Crete School of Medicine
 ( Souglakos John ) - University of Crete School of Medicine Laboratory of Translational Oncology

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 BRAFV600E 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), BRAFV600E 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.

키워드

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