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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Cancer Association
2019
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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. |
format | Online Article Text |
id | pubmed-6790836 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Korean Cancer Association |
record_format | MEDLINE/PubMed |
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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