Tumor Budding in Patients With Colorectal Cancer Under Different MMR Status

Prognostic Impact of Tumor Budding and Tumor-infiltrating Lymphocytes in Patients With Colorectal Cancer Under Different MMR Status: A Single-Center, Open-Label, Retrospective, Observational Cohort Study

This study investigates the ability of tumor budding to identify prognosis in different MMR states and different levels of tumor lymphocyte infiltration. Tumor budding is usually defined as an isolated single cancer cell or a cluster of up to four cancer cells located at the front of an infiltrating tumor.

As a component of the tumor microenvironment, tumor budding is associated with the epidermal mesenchymal transition of tumor cells and may predict disease progression and poor survival. The current assessment of tumor budding levels is mainly based on the ITBCC grading system. The dMMR phenotype of colorectal cancer is associated with the generation of non-self-recognizing neoantigens by the immune system, with tumor-associated extensive inflammatory cell infiltration, and often the dMMR phenotype of colorectal cancer has a lower level of outgrowth, possibly with the generation of local immune responses capable of eradicating tumor budding cells. The prognostic value of the conventional tumor budding grading system has been validated mainly in stage I and II colorectal cancers and does not consider the effect of MMR status on tumor budding. This retrospective study is designed to investigate whether the high grade of tumor budding under high immune response status implies immune escape of tumor cells and brings worse survival outcome, establish a more independent risk grading system to maximize the prognostic value of tumor budding in dMMR phenotype of colorectal cancer in combination with tumor-infiltrating lymphocytes.

Inclusion Criteria:

1. Confirmed colorectal adenocarcinoma cancer pathologically
2. Underwent primary surgery
3. With records for tumor budding staining
4. Willing and able to provide written informed consent for participation in this study
5. Non-complicated primary tumor (complete obstruction, perforation, bleeding)

Exclusion Criteria:

1. With distant metastases at the time of initial diagnosis
2. Without a complete pathological date
3. Hereditary colorectal cancer
4. Subjects with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer