Expression of lox and maspin in colorectal adenocarcinomas and their relationship with tumor microenvironment, molecular profile and prognostic parameters

Introduction: Colorectal cancers are the most common causes of mortality in the world and in our country. New markers are required to support current prognostic parameters in the management of the disease and determining the prognosis. Recently, the microenvironment and molecular profile of the tumor has been investigated more closely. The effectts of maspin and LOX on tumor progression have been searched in distinct tumours. In this study, we investigated the relationship between tumor stroma, tumor budding, poorly differentiated clusters, maspin and LOX expression. We evaluated the correlation between biological behavior of the tumor and expression of maspin and LOX and their realtionship with molecular profile. Material and Method: This study included 101 patients with a diagnosis of colorectal adenocarcinoma in colorectal resection material sent to our laboratory at Ankara City Hospital since February 2019. Mismatch repair protein expression and KRAS, NRAS, BRAF mutation analysis results of these cases were evaluated retrospectively. Tumor slides were reassessed for histopathological features such as tumor budding, desmoplastic stroma pattern, poorly differentiated cell clusters, and immune response to the tumor. Optimal areas were marked at the tumor center and at the invasive border. 3 mm diameter tissue core were removed two for each tumor from the tumor block. A tissue microarray (TMA) blocks were created for Maspin and LOX immunohistochemistry study. Maspin and LOX antibodies were stained immunohistochemically and the results were evaluated. Results were recorded and statistical analysis was performed. Results: In our study, a significant correlation was found between high scores of tumor budding and poor differentiation, frequent lymphovascular invasion and preserved MMR expression. A decrease in overall survival was observed at high tumor budding. High tumor budding and frequent lymphovascular invasion were observed in the immature stroma, when the desmoplastic stroma pattern was evaluated. High LOX expression was associated with decreased progression-free survival in stage IV patients. A significant relationship was found between LOX expression and the degree of poorly differentiated cell clusters (PDC). It was observed that when the LOX expression in the tumor epithelium increased, the LOX expression in the stroma also increased. A significant relationship was found between LOX expression in the stroma and tumor budding, and high levels of budding were detected in high LOX expression. Between the epithelial and stromal expression of LOX and the expression of maspin significant correlation was found. Compared to negative cases, intense stromal LOX expression was correlates to increased mixed and nuclear maspin expression. A significant corelation was detected between nuclear maspin expression and tumor budding, and also mixed maspin expression and lymphovascular invasion. Cytoplasmic maspin expression was found to be associated with decreased overall survival and disease-free survival. Mixed and cytoplasmic expression of maspin was dominant in the right colon carcinomas. Nuclear expression was observed more frequently in left colon tumors. Nuclear expression of maspin was observed not only in tumor buds but also in neoplastic cells in tumor-stroma interaction. We observed that tumor localization assosiacted molecular characteristics, tumor subtype, MMR expression status, and overall survival. Molecular profile was corraleted with tumor subtype and overall survival. Conclusions: This results suggest that tumor budding in colorectal cancers is associated with prognosis on independent of stage and may be closely related to EMT due to its relationship with stroma pattern. The relationship between LOX and maspin was determined, and results were obtained supporting that it is closely related to EMT, which has a critical importance in tumor progression. It has been shown that the histological features of the tumor and its location can reflect the molecular profile, and the effect of histological and molecular features on the prognosis has been determined.