Abstract
BackgroundLaterally spreading tumors (LSTs) are generally defined as lesions >10 mm in diameter, are characterized by lateral expansion along the luminal wall with a low vertical axis. In contrast to other forms of tumor, LSTs are generally considered to have a superficial growth pattern and the potential for malignancy. We focused on this morphological character of LSTs, and analyzed the gene expression profile of LSTs.MethodsThe expression of 168 genes in 41 colorectal tumor samples (17 LST-adenoma, 12 LST-carcinoma, 12 Ip [pedunculated type of the Paris classification)-adenoma, all of which were 10 mm or more in diameter] was analyzed by PCR array. Based on the results, we investigated the expression levels of genes up-regulated in LST-adenoma, compared to Ip-adenoma, by hierarchical and K-means clustering. To confirm the results of the array analysis, using an additional 60 samples (38 LST-adenoma, 22 Ip-adenoma), we determined the localization of the gene product by immunohistochemical staining.ResultThe expression of 129 genes differed in colorectal tumors from normal mucosa by PCR array analysis. As a result of K-means clustering, the expression levels of five genes, AKT1, BCL2L1, ERBB2, MTA2 and TNFRSF25, were found to be significantly up-regulated (p < 0.05) in LST-adenoma, compared to Ip-adenoma. Immunohistochemical analysis showed that the BCL2L1 protein was significantly and meaningfully up-regulated in LST-adenoma compared to Ip-adenoma (p = 0.010). With respect to apoptosis status in LST-Adenoma, it assumes that BCL2L1 is anti-apoptotic protein, the samples such as BCL2L1 positive and TUNEL negative, or BCL2L1 negative and TUNEL positive are consistent with the assumption. 63.2 % LST-adenoma samples were consistent with the assumption.ConclusionsLSTs have an unusual profile of gene expression compared to other tumors and BCL2L1 might be concerned in the organization of LSTs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-015-0295-1) contains supplementary material, which is available to authorized users.
Highlights
Spreading tumors (LSTs) are generally defined as lesions >10 mm in diameter, are characterized by lateral expansion along the luminal wall with a low vertical axis
Laterally spreading tumors (LSTs) have an unusual profile of gene expression compared to other tumors and B cell leukemia/ lymphoma 2-like1 (BCL2L1) might be concerned in the organization of LSTs
Clinical characteristics of tumor samples The 29 LSTs samples were from 15 males (51.7 %) and 14 females (48.3 %), of mean age 69.3 ± 11.8 years, and the mean tumor size was 23.1 ± 12.8 mm
Summary
In contrast to other forms of tumor, LSTs are generally considered to have a superficial growth pattern and the potential for malignancy We focused on this morphological character of LSTs, and analyzed the gene expression profile of LSTs. Colorectal tumors can be morphologically divided into three groups on the basis of their microscopic appearance: protruded-type, depressed-type and laterally spreadingtype tumors [1, 2]. Spreading tumors (LSTs) are generally defined as lesions >10 mm in diameter, are characterized by lateral expansion along the luminal wall with a low vertical axis [3] and are usually divided into two types, granular-type (Gr-LST) and flat- or nongranular-type (NGr-LST), based on morphological differences determined endoscopically. We aimed to determine the gene expression profile of LSTs, which genes are up or down regulated in comparison to polypoid tumors, and to identify the biological pathways involved, such as apoptosis, invasion, metastasis, cell cycling and signal transduction
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