Loss of H2Bub1 Expression is Linked to Poor Prognosis in Nodal Negative Colorectal Cancers.
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.
Department of Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
Nathaniel
N
Melling
Department of Surgery, Regio Hosptital Pinneberg, 25421, Pinneberg, Germany.
Norbert
N
Grimm
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
Ronald
R
Simon
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
Philip
P
Stahl
Department of Oncology, Hematology, BMT with section Pneumology, Hubertus Wald Cancer Center, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
Carsten
C
Bokemeyer
Institute of Pathology, University Hospital Basel, 4001, Basel, Switzerland.
Luigi
L
Terracciano
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
Guido
G
Sauter
Department of Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
Jakob R
JR
Izbicki
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany. a.marx@uke.de.
Andreas H
http://orcid.org/0000-0002-5182-8364
AH
Marx
D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis; D054875:Ubiquitination
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D006657:Histones
Biomarker; Colorectal cancer; Gastrointestinal cancer; Tissue microarray