Microenvironment, systemic inflammatory response and tumor markers considering consensus molecular subtypes of colorectal cancer
Jakab Anna
Pathological Sciences
Dr. Matolcsy András
Patológiai és Kísérleti Rákkutató Intézet Digitális Szövettani Oktatóterem
2024-10-28 15:15:00
Experimental Oncology
Dr. Bödör Csaba
Dr. Micsik Tamás
Dr. Halász Judit
Dr. Szamosi Tamás
Dr. Miheller Pál
Dr. Tőkés Anna-Mária
Dr. Kovács Ildikó
The subject of this thesis was the host reaction against malignancy in colorectal cancer (CRC) patients in relation to one of the latest advancements, the consensus molecular subtypes (CMS). The descriptors of host response in this article were markers of the tissue microenvironment (TME) and systemic inflammatory response (SIR), and additionally, their relation to tumor markers were examined as well.
Of exceptional focus was the tumor-stroma ratio (TSR) amongst TME markers, as it had proven to be one of the most robust, yet convenient HE-based prognosticators. Using a machine learning-based digital image analysis platform, the PatternQuant, TSRsoftware delivered similar prognostic power as TSRvisual while presenting acceptable accuracy and inter rater agreement. TSRvisual helped identifiyfing a subset of CRC patients with rather aggressive phenotype and poor outcome, and was also significantly associated with elevated levels of carcinoembryonic antigen (CEA) and carboanhydrase antigen 19-9 (CA19-9) tumor markers and with CMS4, which was concordant with previous studies. The Klintrup-Makinen (KM) grade was also associated with more advanced stage, however, it didn’t yield significant prognostic power. The combination of KM and TSR, the Glasgow Microenvironment (GMS) score, was similarly associated with adverse clinicopathological features and poorer survival.
Amongst SIR markers, elevated serum C reactive protein (CRP) outstandingly identified cases with adverse histopathological features (stage, lymphatic and vascular invasion) while also being an independent predictor of overal survival (OS), however, it wasn’t associated with any of the TME markers, nor CMS. The modified Glasgow Prognostic Score (mGPS), a combined SIR marker comprising of CRP and albumin also reflected similar associations. Out of the SIR markers, only elevated absolute platelet count (APC) was associated with CMS1, while also showing tendency towards advanced disease.
Strikingly, the authors couldn’t find significant connection between the TME and SIR, which had been expected based on preceding results.
The elevation of CEA and CA19-9 tumor markers also indicated advanced disease and poor outcome. Utilising the combination of the most robust TME marker, the TSR and CA19.9, resulted in the stroma-tumor marker score (STM-score), which stratified the outcome of CRC patients significantly and came out as an independent predictor of OS in the multivariate analysis, while also identifying a group of patients with adverse clinicopathological charateristics.
