Loss of H2Bub1 Expression is Linked to Poor Prognosis in Nodal Negative Colorectal Cancers

TY - JOUR

T1 - Loss of H2Bub1 Expression is Linked to Poor Prognosis in Nodal Negative Colorectal Cancers

AU - Melling, Nathaniel

AU - Grimm, Norbert

AU - Simon, Ronald

AU - Stahl, Phillip

AU - Bokemeyer, Carsten

AU - Terracciano, Luigi

AU - Sauter, Guido

AU - Izbicki, Jakob R

AU - Marx, Andreas H

PY - 2015/9/7

Y1 - 2015/9/7

N2 - To correlate H2Bub1 expression with outcome in colorectal cancer, H2Bub1 expression was analyzed by immunohistochemistry on a tissue microarray containing 1800 colorectal cancers. Results were compared to clinicopathological parameters.H2Bub1 IHC was seen in 1256 (79.3 %) of 1584 interpretable CRC and was considered weak in 26.2 % and strong in 53.1 % of cancers. H2Bub1 expression was completely lost in 20.7 % of the cases. Loss of H2Bub1 expression was associated with high tumor grade (p = 0.0211), high tumor stage (p = 0.0003), positive nodal status (p = 0.0139) and histological tumor type (p = 0.0202). No link was found between H2Bub1 expression and tumor localization (p = 0.1262), peritumoral lymphocytic infiltration (p = 0.2523) or vascular invasion (p = 0.5970).Loss of H2Bub1 expression in CRC was strongly associated with poor patient survival (p = 0.0006). This observation held true also in a subset survival analysis of nodal negative (N0) and nodal positive (N1) cancers (p = 0.0296 and p = 0.0197, respectively). In the subgroup of p53 negative cancers no prognostic impact of H2Bub1 staining was seen (p = 0.1924), whereas in p53 positive CRC H2Bub1 expression loss was associated with poor prognosis (p = 0.0031). Strikingly worsened outcome was found for nodal negative cancers presenting with accumulation of p53 when H2Bub1 expression was lost (p = 0.0006).Our data demonstrate that a reduced H2Bub1 expression is a strong prognostic biomarker both in nodal negative and nodal positive CRC. H2Bub1 expression measurement might help to select nodal negative CRC patients that may benefit from adjuvant therapy.

AB - To correlate H2Bub1 expression with outcome in colorectal cancer, H2Bub1 expression was analyzed by immunohistochemistry on a tissue microarray containing 1800 colorectal cancers. Results were compared to clinicopathological parameters.H2Bub1 IHC was seen in 1256 (79.3 %) of 1584 interpretable CRC and was considered weak in 26.2 % and strong in 53.1 % of cancers. H2Bub1 expression was completely lost in 20.7 % of the cases. Loss of H2Bub1 expression was associated with high tumor grade (p = 0.0211), high tumor stage (p = 0.0003), positive nodal status (p = 0.0139) and histological tumor type (p = 0.0202). No link was found between H2Bub1 expression and tumor localization (p = 0.1262), peritumoral lymphocytic infiltration (p = 0.2523) or vascular invasion (p = 0.5970).Loss of H2Bub1 expression in CRC was strongly associated with poor patient survival (p = 0.0006). This observation held true also in a subset survival analysis of nodal negative (N0) and nodal positive (N1) cancers (p = 0.0296 and p = 0.0197, respectively). In the subgroup of p53 negative cancers no prognostic impact of H2Bub1 staining was seen (p = 0.1924), whereas in p53 positive CRC H2Bub1 expression loss was associated with poor prognosis (p = 0.0031). Strikingly worsened outcome was found for nodal negative cancers presenting with accumulation of p53 when H2Bub1 expression was lost (p = 0.0006).Our data demonstrate that a reduced H2Bub1 expression is a strong prognostic biomarker both in nodal negative and nodal positive CRC. H2Bub1 expression measurement might help to select nodal negative CRC patients that may benefit from adjuvant therapy.

U2 - 10.1007/s12253-015-9977-9

DO - 10.1007/s12253-015-9977-9

M3 - SCORING: Journal article

C2 - 26347467

VL - 22

SP - 95

EP - 102

JO - PATHOL ONCOL RES

JF - PATHOL ONCOL RES

SN - 1219-4956

IS - 1

ER -