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.

Appendiceal Endometriosis with Intestinal Metaplasia Mimicking Appendiceal Mucinous Neoplasm - A Case Report and a Concise Review for the Practicing Pathologist.

Appendiceal endometriosis is a rare entity and, when accompanied by intestinal metaplasia, represents a challenging differential diagnosis with low-grade appendiceal mucinous neoplasm (LAMN). We present the case of a 47 years-old woman, with multiple surgical interventions for endometriosis, with persistent symptoms despite chronic hormonal treatment, with imaging showing stage IV endometriosis. Hence, en bloc low rectum resection with total hysterectomy and bilateral adnexectomy was performed, followed by appendectomy. Unexpectedly, despite the gross normal macroscopic appearance of the appendix, microscopy showed multiple endometriosis foci, consisting of endometrial glands embedded in varying amounts of endometrial stroma. As some of these glands were bordered by mucinous-type epithelium containing intestinal cells, Goblet cells, Paneth cells in addition to the presence of mucus-filled microcysts, immunohistochemistry (IHC) was performed in order to differentiate between intestinal-metaplasia and LAMN. IHC showed positivity of the endometrial epithelium for KRT7, estrogen receptor (ER) and progesterone receptor (PR). Both the appendiceal mucosa and the intestinal-type metaplastic epithelium of the glandular structures were positive for KRT20. Additionally, the endometrial stroma enclosing endometrial glands, as well as the stroma surrounding mucinous-type metaplastic epithelium, were positive for CD10, ER and PR. This patient's case draws attention to the rare occurrence of appendiceal endometriosis and the uncommon intestinal metaplasia, which can easily mimic LAMN, emphasizing the paramount importance of the differential diagnosis with this type of neoplasia.

How to do a laparoscopic high left colectomy with complete mesocolic excision and central vascular ligation for splenic flexure cancer.

Due to a lack of a standardized surgical approach in splenic flexure cancer, we consider useful to present a how to do it material on laparoscopic high left colectomy with complete mesocolic excision and central vascular ligation for this type of tumours.