Molecular Deciphering of Colorectal Cancer: Exploring Molecular Classifications and Analyzing the Interplay among Molecular Biomarkers MMR/MSI, KRAS, NRAS, BRAF and CDX2 - A Comprehensive Literature Review.

Background: Colorectal cancer (CRC) exhibits molecular and morphological diversity, involving genetic, epigenetic alterations, and disruptions in signaling pathways. This necessitates a comprehensive review synthesizing recent advancements in molecular mechanisms, established biomarkers, as well as emerging ones like CDX2 for enhanced CRC assessment. Material and Methods: This review analyzes the last decade's literature and current guidelines to study CRC's molecular intricacies. It extends the analysis beyond traditional biomarkers to include emerging ones like CDX2, examining their interaction with carcinogenic mechanisms and molecular pathways, alongside reviewing current testing methodologies. Results: A multi-biomarker strategy, incorporating both traditional and emerging biomarkers like CDX2, is crucial for optimizing CRC management. This strategy elucidates the complex interaction between biomarkers and the tumor's molecular pathways, significantly influencing prognostic evaluations, therapeutic decision-making, and paving the way for personalized medicine in CRC. Conclusions: This review proposes CDX2 as an emerging prognostic biomarker and emphasizes the necessity of thorough molecular profiling for individualized treatment strategies. By enhancing CRC treatment approaches and prognostic evaluation, this effort marks a step forward in precision oncology, leveraging an enriched understanding of tumor behavior.

Evaluation of the Immunohistochemical Scoring System of CDX2 Expression as a Prognostic Biomarker in Colon Cancer.

Encoded by the CDX2 homeobox gene, the CDX2 protein assumes the role of a pivotal transcription factor localized within the nucleus of intestinal epithelial cells, orchestrating the delicate equilibrium of intestinal physiology while intricately guiding the precise development and differentiation of epithelial tissue. Emerging research has unveiled that positive immunohistochemical expression of this protein shows that the CDX2 gene exerts a potent suppressive impact on tumor advancement in colorectal cancer, impeding the proliferation and distant dissemination of tumor cells, while the inhibition or suppression of CDX2 frequently correlates with aggressive behavior in colorectal cancer. In this study, we conducted an immunohistochemical assessment of CDX2 expression on a cohort of 43 intraoperatively obtained tumor specimens from patients diagnosed with colon cancer at Colțea Clinical Hospital in Bucharest, between April 2019 and December 2023. Additionally, we shed light on the morphological diversity within colon tumors, uncovering varying differentiation grades within the same tumor, reflecting the variations in CDX2 expression as well as the genetic complexity underlying these tumors. Based on the findings, we developed an innovative immunohistochemical scoring system that addresses the heterogeneous nature of colon tumors. Comprehensive statistical analysis of CDX2 immunohistochemical expression unveiled significant correlations with known histopathological parameters such as tumor differentiation grades (p-value = 0.011) and tumor budding score (p-value = 0.002), providing intriguing insights into the complex involvement of the CDX2 gene in orchestrating tumor progression through modulation of differentiation processes, and highlighting its role in metastatic predisposition. The compelling correlation identified between CDX2 expression and conventional histopathological parameters emphasizes the prognostic significance of the CDX2 biomarker in colon cancer. Moreover, our novel immunohistochemical scoring system reveals a distinct subset of colon tumors exhibiting reserved prognostic outcomes, distinguished by their "mosaic" CDX2 expression pattern.

The Effect of Neoadjuvant Radiotherapy on the Pathological Response in Patients with Rectal Cancer.

OBJECTIVE: The aim of this retrospective study was to describe the long-term outcomes and the survival rate in patients who underwent neoadjuvant therapy for rectal cancer. This is a retrospective study undertaken in a surgery department of an oncological clinical hospital. The study evaluated the data of all patients treated for rectal cancer between January 2014 and December 2018. Results: Of 126 patients, thirteen patients with mean age of 58.3 years had a pathological complete response and were treated with neoadjuvant chemoradiotherapy. Ten patients (76.9%) underwent treatment with 45 Gy. One patient was treated with 51 Gy, one with 49.3 Gy, and 12 patients were treated daily with 1.8 Gy. One patient underwent a short course of 5 days with 5 Gy. Patients diagnosed and treated in 2016 had a survival rate of 54 to 57 months, in 2017 42 to 48 months and in 2018 29 to 34 months. For two patients with final pCR, the adjuvant treatment was given and the wait and watch policy was applied. Both patients were females, aged 51 and 66 years (mean age 58.5 years). CONCLUSION: The frequency of pCR was similar to that in other published studies. The survival rate in our cohort was high, death occurring in two cases, one being the oldest patient in the study. We concluded that the long-term oncological control is excellent in patients who receive neoadjuvant treatment leading to improved OS, improved quality of life, and decreasing the recurrence rates.