Abstract
BackgroundIn contrast to sessile serrated adenomas and traditional serrated adenomas which are associated with a significant cancer risk, the role of hyperplastic polyps (HP) in colorectal carcinogenesis as well as the molecular mechanisms underlying their development remain controversial and still need to be clarified. Several reports suggest that a subset of HP may represent precursor lesions of some colorectal cancers. However, biomarkers are needed to identify the subset of HP that may have a malignant potential. The hormone precursor, progastrin (PG) has been involved in colon carcinogenesis and is known to activate pro-oncogenic pathways such as the ERK or the STAT3 pathway. We therefore analyzed PG expression and the activation of these signaling factors in HP.MethodsWe retrospectively analyzed PG expression as well as the phosphorylation of ERK and STAT3 by immunohistochemistry in HP from 48 patients.ResultsMean percentages of epithelial cells positive for PG or phospho-ERK were respectively, 31% and 33% in HP and were significantly higher in these lesions compared to normal colon (3%, p = 0.0021 and 7%, p = 0.0008, respectively). We found a significant correlation between PG and phospho-ERK expression in HP with ERK activation significantly stronger in lesions with high progastrin expression (p = 0.015). In contrast, STAT3 was not significantly activated in HP compared to normal colon and we did not observe a significant correlation with PG expression.ConclusionsHP overexpressing PG that have the highest activation of the ERK pathway might reflect less latent lesions that might have a malignant potential.
Highlights
In contrast to sessile serrated adenomas and traditional serrated adenomas which are associated with a significant cancer risk, the role of hyperplastic polyps (HP) in colorectal carcinogenesis as well as the molecular mechanisms underlying their development remain controversial and still need to be clarified
To take into account the heterogeneity of PG staining in HP observed in Figure 1, PG expression was analyzed in Table 1 as a 3 classes variable as detailed in “Methods”
No/low expression of progastrin was observed in 44% of the HP, moderate expression in 25% (14%-40%) and strong expression in 31% (19%-46%)
Summary
In contrast to sessile serrated adenomas and traditional serrated adenomas which are associated with a significant cancer risk, the role of hyperplastic polyps (HP) in colorectal carcinogenesis as well as the molecular mechanisms underlying their development remain controversial and still need to be clarified. The serrated adenomas represent a heterogeneous group of lesions including, sessile serrated adenomas (SSA) and traditional serrated adenomas (TSA). They are associated with a significant cancer risk and represent neoplastic precursor lesion of serrated adenocarcinomas [1,2]. Both SSA and TSA have a high frequency of DNA methylation. HP from patients who developed adenomas overexpressed the prohormone progastrin (PG) which is recognized as a growth factor, playing an important role in colon carcinogenesis [12]
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