Histopathological and tumor microenvironment analysis in colorectal cancer: integrating morphology with molecular oncology: A systematic review

Colorectal cancer (CRC) is an important cancer burden around the world, and a leading cause of cancer-related death, and is increasing in incidence in a wide range of populations. Although advances have been made in diagnosis and therapeutic interventions, there is still a lack of uniformity in diagnostics, which makes risk stratification and treatment selection difficult. In this context, the inclusion of molecular diagnostics in the histopathological evaluation has come to be a keystone in precision oncology in CRC.
This systematic review aims to critically summarise the more recent developments in molecular typing and histopathological assessment, highlighting their complementary value in the current diagnosis of CRC. New molecular methods such as next generation sequencing, microsatellite instability and circulating tumor DNA profiling have greatly improved detection of actionable genetic changes and patient stratification. At the same time, histopathological methods continue to be a cornerstone for tumor grading and staging, and their interpretation is supported by immunohistochemistry and, increasingly, by well-established systems of morphological classification.
The multimodal approach allows for a comprehensive characterization of the tumor heterogeneity that combines morphological and genetic aspects. Importantly, integrated diagnostic frameworks have shown to have greater prognostic accuracy and better aid in therapeutic decision making, especially with regard to targeted therapy, and immunotherapy.
However, the clinical application is limited due to infrastructural problems, varying costs, and the necessity of standardized interpretation. Areas to be emphasized include harmonization of integrated diagnostic protocol and availability of more wider-spread molecular platforms for realizing precision-based colorectal cancer management.