Immunohistochemistry predictive markers for primary colorectal cancer tumors: where are we and where are we going?

The aim of our study is to highlight and organize the recently published immunohistochemistry (IHC) predictive biomarkers of primary colorectal cancers (CRCs) that could lead to practical implementation. We reviewed articles that examined CRC samples with significant statistic correlation between the IHC marker expression and disease progression over time, relationships with the available clinical features and those who detect the prognosis of drug effects. Our analysis showed that nine markers could correlate with medical treatment response of CRCs in different stages. When using better overall survival (OS) and better disease-free survival (DFS) as a grouping factor, there were 14 markers that could be used in assessing CRC prognosis. By using poor prognostic for the OS and the DFS as a grouping factor, we found 43 markers. Subgroup analysis was also performed based on the 32 markers recently confirmed to predict metastasis evolution or the recurrence risks. Venous invasion could be predictable for tumors, statistically significant metastasis susceptibility was observed for markers and also the capacity to evaluate recurrence. CRCs integrate a variety of localizations and there are proofs that distinguish the sites of tumors. The studies reporting data specifically for rectal cancer separating it from colon cancer contained seven IHC markers. In order to be able to implement a predictive biomarker in clinical practice, it must comply with certain criteria as clinical value and analytical proof. Unique biological signature of CRC can be distinguished by identifying biomarkers expression. Several markers have shown potential, but the majority still need to render clinical utility.

CD133/CD166/Ki-67 triple immunofluorescence assessment for putative cancer stem cells in colon carcinoma.

BACKGROUND & AIMS: Colorectal cancer represents the third most common malignancy and the fourth most common cause of cancer death worldwide. The existence of drug-resistant colon cancer stem cells is thought to be one of the most important reasons behind treatment failure in colon cancer, their existence putatively leading to metastasis and recurrences. The aim of our study was to investigate the immunoexpression patterns of CD133 and CD166 in colon carcinoma, both individually and in combination, assessing their significance as prognostic markers. METHODS: A total of 45 retrospective colon adenocarcinoma cases were investigated by enzymatic and multiple fluorescence immunohistochemistry for their CD133 and CD166 expression and colocalization. RESULTS: Both CD133 and CD166 were expressed to different extents in all cancer specimens, with a predominant cytoplasmic pattern for CD133 and a more obvious membranous-like pattern for CD166. Overall, when comparing their reactivity for the tumoral tissue, CD166 expression areas seemed to be smaller than those of CD133. However, there was a direct correlation between CD133 and CD166 expression levels throughout the entire spectrum of lesions, with higher values for dysplastic lesions. Colocalization of CD133/CD166 was obvious at the level of cells membranes, with higher coefficients in high grade dysplasia, followed by well and moderate differentiated tumours. : CD133/CD166 colocalization is an early event occurring in colon tumorigenesis, with the highest coefficients recorded for patients with high grade dysplasia, followed by well differentiated tumours. Thus, we consider that the coexpression of these two markers could be useful for further prognostic and therapeutically stratification of patients with colon cancer.

Serum and tumor microenvironment IL-8 values in different stages of colorectal cancer.

INTRODUCTION: Colorectal cancer represents a major cause of mortality and morbidity and occupies the third place as cancer incidence and the fourth place as cancer mortality. Colorectal cancer causes 608 000 deaths per year, despite correct applied treatment (surgery and chemotherapy). Interleukin 8 (IL-8) is an important proinflammatory cytokine with an important role in leukocyte chemoattraction. IL-8 also represents an important tumorigenic and proangiogenic factor. MATERIALS AND METHODS: We have studied 68 patients aged between 55 and 70 years, hospitalized in the IInd Surgery Clinic of the Emergency County Hospital of Craiova, Romania. According to TNM grading, the patients were in stages II, III and IV. From these patients, we have prelevated two types of samples: serum and tumor fragment. RESULTS: IL-8 values were significantly increased, both in serum and tumor supernatant. The highest IL-8 values were found in tumor supernatant and in advanced stages; IL-8 increased values were correlated with tumor growth and TNM stage. CONCLUSIONS: IL-8 has an important role in colorectal cancer growth and metastasis and represents an important therapeutic target in this type of cancer. IL-8 represents also a predictor for colorectal cancer prognosis.

Determination of autophagy gene ATG16L1 polymorphism in human colorectal cancer.

Autophagy has emerged not only as an essential repair mechanism to degrade damaged organelles and proteins but also as a major player in protection of tumor cells from multiple stresses. It was shown that autophagy gene polymorphisms are correlated with development of chronic inflammatory lesions, which represent a risk factor for colorectal tumors. In this study, we aimed to determine if ATG16L1 +898A>G (Thr300Ala) polymorphism is associated with an increased risk of developing colorectal cancer (CRC) and to establish correlations between ATG16L1 genotypes and the major clinical and morphological parameters. We observed that subjects carrying GG genotype were at a higher risk for CRC (OR 1.99, 95% CI: 1.02-3.91, p=0.039) when compared with the more frequent AA genotype, furthermore this was even more consistent in male subjects (OR 2.72, 95% CI: 1.11-6.63, p=0.019) but not in female subjects (OR 1.29, 95% CI: 0.43-3.86, p=0.652). In addition, we noticed a correlation between ATG16L1 GG genotype and tumor stage in moderately and poorly differentiated CRC cases. GG genotype carrying patients were at a higher risk for CRC (OR 5.19, 95% CI: 1.50-17.87, p=0.002) when compared with the more frequent AA genotype. Such correlation suggests a possible role of autophagy gene polymorphisms in the development of human colorectal cancer.