Immunohistochemical patterns in rectal cancer: Application of tissue microarray with prognostic correlations

Abstract

We utilized the high-throughput tissue microarray method to characterize immunohistochemical expression patterns with correlations to prognosis in rectal cancer. Immunostaining for the markers Ki-67, Bcl-2, p53, EGFR, Ecadherin, ␤-catenin, MLH1 and MSH2 was performed in 269 rectal cancers. Expression profiles were correlated to metastasis-free survival. Colorectal cancer is estimated to be the second leading cause of cancer death worldwide. 1 Differences in etiology, clinical behavior, pathologic features and genetic alterations apply to right-sided vs. left-sided colorectal tumors, which indicate that different mechanisms drive tumorigenesis at these sites. 2,3 Approximately 35% of colorectal cancers are located in the rectum, and rectal cancer affects males at a rate of 1.5:1 compared to females, with 75% of cases diagnosed after 65 years of age. Treatment advances such as the standardized surgical technique TME, preoperative radiotherapy and adjuvant chemotherapy have reduced the previously high local recurrence rate and improved survival in rectal cancer patients. Despite these advances, about 40% of patients still die from disseminated disease. 4 -6 Hence, there is a need for novel markers that allow improved identification of high-risk patients who would benefit from adjuvant treatment. 7 Colorectal cancer is one of the best-characterized tumor types at the molecular level. Numerous genetic alterations in oncogenes, tumor-suppressor genes and DNA MMR genes are acquired during tumorigenesis, which occurs through successive waves of clonal expansion according to 2 major mutational pathways, the CIN and MSI pathways. 8,9 Although the sequential accumulation of genetic changes that characterize the adenoma-carcinoma sequence of colorectal cancer applies also to rectal cancer, few studies have separately analyzed these tumor types. Rectal cancer has been associated with high proliferative activity, frequent aneuploidy and loss of heterozygosity at 17p and 18q, mutation/overexpression of p53 and consequently low frequencies of diploid tumors and MSI. 2,3,10 -12 Since the frequencies of the different genetic alterations vary according to tumor location within the bowel, studies investigating a possible prognostic role of biologic parameters should optimally analyze these tumor types separately.Several tumor-associated proteins may be relevant prognostic markers in rectal cancer. However, no single molecular marker has been demonstrated to provide consistent and independent prognostic information, and despite advances in our understanding of the pathogenesis of rectal cancer, molecular markers have not gained utility in clinical decision making. 7,13,14 The TMA technology allows high-throughput analysis of molecular markers and thereby facilitates studies of multiple markers in large tumor series. 15 Our aim was to apply TMA to investigate the expression patterns of multiple markers and their prognostic correlations in a large series of rectal cancer patients. These markers, which included Ki-67, p53, Bcl-2, EGF...

An Increased Expression of Cysteinyl Leukotriene 2 Receptor in Colorectal Adenocarcinomas Correlates with High Differentiation

“…Although colorectal cancer is the third most common cancer in the Western world, there is a current lack of good prognostic markers in clinical use despite different markers being suggested in the literature (47,48). In addition to our present finding that CysLT 2 R can induce differentiation, we also show in the present study that the expression of CysLT 2 R is reduced in colon cancer cell lines compared with nontransformed intestinal epithelial cell lines.…”

Combination of p53 expression and p21 loss has an independent prognostic impact on sporadic colorectal cancer

“…Additionally, we observed that patients with p53-positive carcinomas tended to have a better recurrence-free survival. In contrast, other studies found an association of p53 positivity and higher risk of tumor relapse as well as no relation to tumor recurrence (12,13,27,29,31). The discrepancies between patient outcomes may depend on the tumor location (proximal vs. distal), p53 mutation site, tumor type and response to adjuvant therapy.…”

Epithelial Human Leukocyte Antigen-DR Expression Predicts Reduced Recurrence Rates and Prolonged Survival in Rectal Cancer Patients

“…However, stratified analyses according to tumor location revealed better prognosis for HLA-DR -positive tumors in colon cancer patients but not in rectal cancer patients (9). The prognostic value of HLA-DR obtained in colorectal patients might be skewed by its association with microsatellite instability (9), which is a rare event in rectal tumors (24,25). To our knowledge, this is the first comprehensive study investigating a correlation between epithelial HLA-DR expression and survival of rectal cancer patients.…”