PhD Scientific Days 2021

PO_I_P: Pathology and Oncology I. Posters

Preliminary study of inflammasomes activity and growth patterns in colorectal adenocarcinoma liver metastases

Text of the abstract

Introduction: Almost half of colorectal carcinoma patients develop liver metastases (CRCLM) during their illness. It is well established that metastases have well distinguishable growth patterns (replacement, desmoplastic, pushing and mixed). The appearance of the replacement type is accompanied by the worst outcome. However, It is unknown how the growth patterns are influenced by the local inflammatory response.

Aims: To assess the link between tumour infiltrating and peritumoral lymphocyte activity and tumour growth pattern in CRCLM specimens.

Methods: Formalin fixed, paraffin embedded histology samples of CRCLM were assessed (n = 93). Histologically the growth pattern analysis of the metastases were performed alongside the evaluation of the mass of tumour infiltrating lymphocytes (TIL) and peritumoral lymphocytes (PTL), and tumour regression rate. Furthermore NLRP3/ASC immunofluorescent staining was performed on the specimens to evaluate inflammasome activity. Histological evaluation was performed digitally by Orbit platform. All extracted data was correlated with clinical parameters such as type and severity of surgery, or type of neoadjuvant treatment where it was applicable.

Results: In 78,4% of all specimens (n=73) replacement type tumour growth was found regardless of the received neoadjuvant treatment. Strong correlation was shown between the size of peritumoral lymphocytic infiltration and of the receiving of neoadjuvant treatment (r=0.64). Interestingly, TILs seemed to be lessened in neoadjuvant treated patients, regardless of the type of used pharmaceuticals (r=0.41). ASC/NLRP3 expression was strongest in tumours with replacement growth pattern and weakest in desmoplastic type (p<0.001), while pushing and mixed types showed intermediate expression rates. The expression of ASC showed strong positive correlation to the mass of PTL infiltration (r= 0.62).

Conclusion: Our results suggest that the appearance of distinct growth patterns in CRCLM is linked to the NLRP3 inflammasome based chronic inflammatory response, which might be heavily influenced by the neoadjuvant treatment.

Funding: ÚNKP-20-4-II-SE-28

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