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Tumor MHC class I expression improves the prognostic value of T-cell density in resected colorectal liver metastases.

ABSTRACT: Tumor-infiltrating lymphocytes (TIL) in colorectal cancer liver metastases (CLM) have been associated with more favorable patient outcomes, but whether MHC class I (MHC-I) expression on cancer cells affects prognosis is uncertain. Immunohistochemistry was performed on a tissue microarray of 158 patients with CLM, who underwent partial hepatectomy with curative intent. Using the antibody HC-10, which detects HLA-B and HLA-C antigens and a minority of HLA-A antigens, MHC-I expression was correlated with ?-2 microglobulin (?2m; r = 0.7; P < 0.001), but not with T-cell density (r < 0.32). The median follow-up for survivors was 9.7 years. High levels of MHC-I expression in tumors concomitant with high T-cell infiltration (CD3, CD4, or CD8) best identified patients with favorable outcomes, compared with patients with one or none of these immune features. The median overall survival (OS) of patients with MHC-I(hi)CD3(hi) tumors (n = 31) was 116 months compared with 40 months for the others (P = 0.001), and the median time to recurrence (TTR) was not reached compared with 17 months (P = 0.008). By multivariate analysis, MHC(hi)CD3(hi) was associated with OS and TTR independent of the standard clinicopathologic variables. An immune score that combines MHC-I expression and TIL density may be a valuable prognostic tool in the treatment of patients with CLM.

SUBMITTER: Turcotte S

PROVIDER: S-EPMC4048875 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Tumor MHC class I expression improves the prognostic value of T-cell density in resected colorectal liver metastases.

Turcotte Simon S Katz Steven C SC Shia Jinru J Jarnagin William R WR Kingham T Peter TP Allen Peter J PJ Fong Yuman Y D'Angelica Michael I MI DeMatteo Ronald P RP

Cancer immunology research 20140220 6

Tumor-infiltrating lymphocytes (TIL) in colorectal cancer liver metastases (CLM) have been associated with more favorable patient outcomes, but whether MHC class I (MHC-I) expression on cancer cells affects prognosis is uncertain. Immunohistochemistry was performed on a tissue microarray of 158 patients with CLM, who underwent partial hepatectomy with curative intent. Using the antibody HC-10, which detects HLA-B and HLA-C antigens and a minority of HLA-A antigens, MHC-I expression was correlate ...[more]

PMID: 24894090

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Project description:UnlabelledIntegrins are cell surface adhesion molecules (CAM) that regulate via intercellular and cell-matrix signaling various cellular processes including wound healing, cell differentiation, division, growth, migration and metastatic dissemination. Although a correlation between carcinogenesis and changes in integrin expression, especially ?1 integrin, has been reported, its role in colorectal liver metastases remains unclear. This study aimed to evaluate the expression of ?1 integrin in colorectal liver metastases and to correlate the pattern of expression with clinicopathological features and to investigate the putative role of ?1 integrin expression on survival of these patients.MethodsFormalin-fixed, paraffin-embedded (FFPE) tumor samples of 81 patients who were operated because of colorectal liver metastases without any neoadjuvant therapy were obtained and stained with hematoxylin and eosin (H & E). An immunohistochemical examination was performed using Dako, Peroxidase/DAB kit and a primary monoclonal ?1 integrin (CD29, fibronectin receptor subunit beta; ab3167, Abcam plc). ?1 integrin expression was evaluated according to the immunoreactive score of Remmele and Stegner and was related with clinicopathological features of prognostic significance and with disease-free and overall survival as well. Statistical analysis was performed using SPSS version 21.0.Results?1 integrin was overexpressed in tumor cells in 37 (48%) patients and in stromal cell in 27 (33%) patients. The ?1 expression was not statistically correlated with clinicopathological features of the primary tumors but it was statistically correlated (p=0.03) with the histological grading of liver metastases. Kaplan-Meier survival analysis showed that there is a tendency but no statistically significant correlation in disease-free and overall survival.ConclusionConsidering that expression of ?1 integrin in colorectal liver metastases remains controversial, specially its relation with survival of patients, we showed that the ?1 expression represents a reliable prognostic factor regarding the grading of liver metastases of CRC and our findings imply that ?1 integrin expression profiles may have further potential in identifying the stage of colorectal liver metastases and being a marker of prognosis in these patients.

Project description:BackgroundResection of colorectal cancer liver metastasis (CRCLM) with curative intent has long-term benefit in ~40% of cases. Prognostic biomarkers are needed to improve clinical management and reduce futile surgeries. Expression of epidermal growth factor receptor (EGFR) and prostaglandin-endoperoxide synthase 2 (PTGS2; also known as cyclooxygenase-2) has been associated with carcinogenesis and survival. We investigated the prognostic value of EGFR and PTGS2 expression in patients with resected CRCLM.MethodsFormalin-fixed paraffin-embedded CRCLM tissue and corresponding primary tumour specimens from a multi-institutional cohort of patients who underwent liver resection between 1990 and 2010 were incorporated into tissue microarrays (TMAs). TMAs were stained for EGFR and PTGS2 by immunohistochemistry. The hazard rate ratio (HRR) for the association between expression in CRCLM and overall survival was calculated using a 500-fold cross-validation procedure.ResultsEGFR and PTGS2 expression could be evaluated in 323 and 351 patients, respectively. EGFR expression in CRCLM was associated with poor prognosis (HRR 1.54; P<0.01) with a cross-validated HRR of 1.47 (P=0.03). PTGS2 expression was also associated with poor prognosis (HRR 1.60; P<0.01) with a cross-validated HRR of 1.63 (P<0.01). Expression of EGFR and PTGS2 remained prognostic after multivariate analysis with standard clinicopathological variables (cross-validated HRR 1.51; P=0.02 and cross-validated HRR 1.59; P=0.01, respectively). Stratification for the commonly applied systemic therapy regimens demonstrated prognostic value for EGFR and PTGS2 only in the subgroup of patients who were not treated with systemic therapy (HRR 1.78; P<0.01 and HRR 1.64; P=0.04, respectively), with worst prognosis when both EGFR and PTGS2 were highly expressed (HRR 3.08; P<0.01). Expression of PTGS2 in CRCLM was correlated to expression in patient-matched primary tumours (P=0.02, 69.2% concordance).ConclusionsEGFR and PTGS2 expressions are prognostic molecular biomarkers with added value to standard clinicopathological variables for patients with resectable CRCLM.

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Tumor MHC class I expression improves the prognostic value of T-cell density in resected colorectal liver metastases.

Publications

Tumor MHC class I expression improves the prognostic value of T-cell density in resected colorectal liver metastases.

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