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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

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 surgic...

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Autores principales: Sfakianaki, Maria, Papadaki, Chara, Tzardi, Maria, Trypaki, Maria, Alam, Sardar, Lagoudaki, Eleni D., Messaritakis, Ippokratis, Zoras, Odysseas, Mavroudis, Dimitris, Georgoulias, Vassilis, Souglakos, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Cancer Association 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790836/
https://www.ncbi.nlm.nih.gov/pubmed/30913862
http://dx.doi.org/10.4143/crt.2019.008
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author Sfakianaki, Maria
Papadaki, Chara
Tzardi, Maria
Trypaki, Maria
Alam, Sardar
Lagoudaki, Eleni D.
Messaritakis, Ippokratis
Zoras, Odysseas
Mavroudis, Dimitris
Georgoulias, Vassilis
Souglakos, John
author_facet Sfakianaki, Maria
Papadaki, Chara
Tzardi, Maria
Trypaki, Maria
Alam, Sardar
Lagoudaki, Eleni D.
Messaritakis, Ippokratis
Zoras, Odysseas
Mavroudis, Dimitris
Georgoulias, Vassilis
Souglakos, John
author_sort Sfakianaki, Maria
collection PubMed
description 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.
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spelling pubmed-67908362019-10-21 Loss of LKB1 Protein Expression Correlates with Increased Risk of Recurrence and Death in Patients with Resected, Stage II or III Colon Cancer Sfakianaki, Maria Papadaki, Chara Tzardi, Maria Trypaki, Maria Alam, Sardar Lagoudaki, Eleni D. Messaritakis, Ippokratis Zoras, Odysseas Mavroudis, Dimitris Georgoulias, Vassilis Souglakos, John Cancer Res Treat Original Article 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. Korean Cancer Association 2019-10 2019-03-20 /pmc/articles/PMC6790836/ /pubmed/30913862 http://dx.doi.org/10.4143/crt.2019.008 Text en Copyright © 2019 by the Korean Cancer Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Sfakianaki, Maria
Papadaki, Chara
Tzardi, Maria
Trypaki, Maria
Alam, Sardar
Lagoudaki, Eleni D.
Messaritakis, Ippokratis
Zoras, Odysseas
Mavroudis, Dimitris
Georgoulias, Vassilis
Souglakos, John
Loss of LKB1 Protein Expression Correlates with Increased Risk of Recurrence and Death in Patients with Resected, Stage II or III Colon Cancer
title Loss of LKB1 Protein Expression Correlates with Increased Risk of Recurrence and Death in Patients with Resected, Stage II or III Colon Cancer
title_full Loss of LKB1 Protein Expression Correlates with Increased Risk of Recurrence and Death in Patients with Resected, Stage II or III Colon Cancer
title_fullStr Loss of LKB1 Protein Expression Correlates with Increased Risk of Recurrence and Death in Patients with Resected, Stage II or III Colon Cancer
title_full_unstemmed Loss of LKB1 Protein Expression Correlates with Increased Risk of Recurrence and Death in Patients with Resected, Stage II or III Colon Cancer
title_short Loss of LKB1 Protein Expression Correlates with Increased Risk of Recurrence and Death in Patients with Resected, Stage II or III Colon Cancer
title_sort loss of lkb1 protein expression correlates with increased risk of recurrence and death in patients with resected, stage ii or iii colon cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790836/
https://www.ncbi.nlm.nih.gov/pubmed/30913862
http://dx.doi.org/10.4143/crt.2019.008
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