Abstract
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.
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Nathaniel Melling and Norbert Grimm contributed equally to this study.
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Melling, N., Grimm, N., Simon, R. et al. Loss of H2Bub1 Expression is Linked to Poor Prognosis in Nodal Negative Colorectal Cancers. Pathol. Oncol. Res. 22, 95–102 (2016). https://doi.org/10.1007/s12253-015-9977-9
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DOI: https://doi.org/10.1007/s12253-015-9977-9