An exploration of immunohistochemistry-based prognostic markers in patients undergoing curative resections for colon cancer.

BACKGROUND: The immune system recognizes and destroys cancer cells. However, cancer cells develop mechanisms to avoid detection by expressing cell surface proteins. Specific tumour cell surface proteins (e.g. HLA-G, PD-L1, CDX2) either alone or in combination with the relative presence of immune cells (CD3 and CD8 positive T-cells) in the tumour tissue may describe the cancer cells' ability to escape eradication by the immune system. The aim was to investigate the prognostic value of immunohistochemical markers in patients with colon cancer. METHODS: We conducted a retrospective study including patients diagnosed with pT3 and pT4 colon cancers. Immunohistochemical staining with HLA-G, PD-L1, CDX2, CD3, and CD8 was performed on tissue samples with representation of the invasive margin. PD-L1 expression in tumour cells and immune cells was reported conjointly. The expression of CD3 and CD8 was reported as a merged score based on the expression of both markers in the invasive margin and the tumour centre. Subsequently, a combined marker score was established based on all of the markers. Each marker added one point to the score when unfavourable immunohistochemical features was present, and the score was categorized as low, intermediate or high depending on the number of unfavourable stains. Hazard ratios for recurrence, disease-free survival and mortality were calculated. RESULTS: We included 188 patients undergoing colon cancer resections in 2011-2012. The median follow-up was 41.7 months, during which 41 (21.8%) patients had recurrence and 74 (39.4%) died. In multivariable regression analysis positive HLA-G expression (HR = 3.37, 95%CI [1.64-6.93]) was associated with higher recurrence rates, while a preserved CDX2 expression (HR = 0.23, 95%CI [0.06-0.85]) was associated with a lower risk of recurrence. An intermediate or high combined marker score was associated with increased recurrence rates (HR = 20.53, 95%CI [2.68-157.32] and HR = 7.56, 95%CI [1.06-54.16], respectively). Neither high expression of PD-L1 nor high CD3-CD8 score was significantly associated with recurrence rates. Patients with a high CD3-CD8 score had a significantly longer DFS and OS. CONCLUSIONS: In tumour cells, expression of HLA-G and loss of CDX2 expression were associated with cancer recurrence. In addition, a combination of certain tumour tissue biomarkers was associated with colorectal cancer recurrence.

Post-operative recovery is not a limiting factor for adjuvant chemotherapy in patients undergoing surgery for colorectal cancer.

INTRODUCTION: Little is known about factors affecting the initiation of adjuvant chemotherapy (AC) after minimally invasive surgery. The aim of this study was to describe the ratio of patients undergoing uncomplicated colorectal cancer surgery in a standardised enhanced recovery after surgery setting receiving AC. Furthermore, the association between post-operative quality of recovery and initiation of AC was investigated. METHODS: This was a prospective study. Post-operative recovery was measured with the Quality of Recovery-15 questionnaire preoperatively, post-operatively on day 1, at discharge and on post-operative day 30. RESULTS: A total of 115 patients were included between October 2016 and May 2017. Among these, 20 patients were excluded. Hence, 95 patients were followed up as uncomplicated cases. The median length of stay was three days (interquartile range: 2-4). A total of 40 patients were referred for oncological evaluation, but nine patients did not proceed to receive AC. Among the 31 patients starting AC, 48% (n = 15) received AC less-than 4 weeks and 52% (n = 16) > 4 weeks. No significant difference was seen in post-operative quality of recovery, either when investigating the full cohort or subgroups of patients who initiated AC before and after four weeks. CONCLUSIONS: Post-operative recovery may not be the factor limiting patients from receiving adjuvant chemotherapy either before or after post-operative week four. FUNDING: none. TRIAL REGISTRATION: The study was approved by the Data Protection Agency (reg. no. REG044-2018).