Two-marker protein profile predicts poor prognosis in patients with early rectal cancer

Abstract

The aim of this study was to establish an immunohistochemical protein profile to complement preoperative staging and identify rectal cancer patients at high-risk of adverse outcome. Immunohistochemistry was performed on a tissue microarray including 482 rectal cancers for APAF-1, EphB2, MST1, Ki67, p53, RHAMM, RKIP and CD8 þ tumour infiltrating lymphocytes (TILs). After resampling of the data and multivariable analysis, the most reproducible markers were combined and prognosis evaluated as stratified by pT and pN status. In multivariable analysis, only positive RHAMM (Po0.001; HR ¼ 1.94 (1.44 -2.61)) and loss of CD8 þ TILs (P ¼ 0.006; HR ¼ 0.63 (0.45 -0.88)) were independent prognostic factors. The 5-year cancer-specific survival rate for RHAMM þ /TILÀ patients was 30% (95% CI 21 -40%) compared to 76% (95% CI: 66 -84%) for RHAMMÀ/TIL þ patients (Po0.001). The 5-year cancerspecific survival of T1/T2/RHAMM þ /TILÀ patients was 48% (20 -72%) and significantly worse compared to T3/T4/RHAMMÀ/ TIL þ patients (71% 95% CI 56 -82%); P ¼ 0.039). Stratifying by nodal status, only N þ /RHAMM þ /TILÀ patients demonstrated a significantly worse prognosis than N0/RHAMM þ /TILÀ patients (P ¼ 0.005). Loss of CD8 þ TILs was predictive of local recurrence in RHAMM þ tumours (P ¼ 0.009) only. RHAMM and CD8 þ TILs may assist in identifying early stage rectal cancer patients facing a particularly poor prognosis and who may derive a benefit from preoperative therapy.

RAF-kinase inhibitor protein (RKIP) downregulation in esophageal cancer and its metastases

“…Our findings in esophageal AC establishing RKIP downregulation as an important independent prognostic factor, are in agreement with results in a variety of human ACs, including nasopharyngeal, colorectal, breast and prostate cancer, where RKIP downregulation was associated with rapid tumor progression and worse prognosis [20][21][22][23][24]. Interestingly, RKIP expression was of no prognostic relevance in a series of diffuse gastric cancers in contrast to intestinal ones [25].…”

Active immunosurveillance in the tumor microenvironment of colorectal cancer is associated with low frequency tumor budding and improved outcome

“…For CD81 T-cell counts, a previously published receiver operating characteristic (ROC) curve-derived cutoff score was used for low vs high T-cell counts (cutoff 13 or more cells per spot on average, high; up to 12 cells, low). 26 Similarly, TIA1 counts were considered low when an average of up to 10 cells per punch was observed, whereas high counts were assigned when more than 10 cells per punch were counted. 3 Molecular analysis.…”

Characterization of rectal, proximal and distal colon cancers based on clinicopathological, molecular and protein profiles

“…Analysis for BRAF, K-RAS and MSI status are routinely performed at the Institute of Pathology, University Hospital Basel, Switzerland. A detailed protocol has previously been described (15). Microsatellite stable (MSS) and MSI-low (MSI-L) status were defined as instability at 0 and 1 markers, respectively.…”