Intratumoral Budding in Pretreatment Biopsies, among Tumor Microenvironmental Components, Can Predict Prognosis and Neoadjuvant Therapy Response in Colorectal Adenocarcinoma

Abstract

Background and Objectives: The prediction of the prognosis and effect of neoadjuvant therapy is vital for patients with advanced or unresectable colorectal carcinoma (CRC). Materials and Methods: We investigated several tumor microenvironment factors, such as intratumoral budding (ITB), desmoplastic reaction (DR), and Klintrup–Mäkinen (KM) inflammation grade, and the tumor–stroma ratio (TSR) in pretreatment biopsy samples (PBSs) collected from patients with advanced or unresectable CRC. A total of 85 patients with 74 rectal carcinomas and 11 colon cancers treated at our hospital were enrolled; 66 patients had curative surgery and 19 patients received palliative treatment. Results: High-grade ITB was associated with recurrence (p = 0.002), death (p = 0.034), and cancer-specific death (p = 0.034). Immature DR was associated with a higher grade of clinical tumor-node-metastasis stage (cTNM) (p = 0.045), cN category (p = 0.045), and cM category (p = 0.046). The KM grade and TSR were not related to any clinicopathological factors. High-grade ITB had a significant relationship with tumor regression in patients who received curative surgery (p = 0.049). Conclusions: High-grade ITB in PBSs is a potential unfavorable prognostic factor for patients with advanced CRC. Immature DR, TSR, and KM grade could not predict prognosis or therapy response in PBSs.

The Role of Galectin3, Tubulinβ, and Maspin in Promoting Tumor Budding in Colorectal Carcinoma and Their Clinical Implications

“…CRC is a major cause of morbidity and mortality all over the world 1 . TB has been verified as one of the important prognostic parameters and a positive anticipating factor in many cancers, including colon cancer in which it might help to choose high-risk patients indicated for neoadjuvant therapy 5,14 …”

“…1 TB has been verified as one of the important prognostic parameters and a positive anticipating factor in many cancers, including colon cancer in which it might help to choose high-risk patients indicated for neoadjuvant therapy. 5,14 TB is defined as the presence of a single tumor cell or a cluster formed of 4 tumor cells or less within the stroma. TB could be seen in the stroma of tumor center (intratumoral budding) or at the invasive tumor front (peritumoral budding).…”

“…TB quantification is mainly estimated on hematoxylin and eosin slides. Cytokeratin immunohistochemical staining was sometimes used to count tumor buds if masked by dense inflammation but is not recommended 5,6 …”

“…4 Tumor microenvironment (TME) was considered to play an influential role in regulating tumor behavior and response to therapy. TME of solid tumors includes different components such as tumor budding (TB) 5 tumor-associated immune cells, and tumor-associated endothelial cells. 6 The identification of TB in pretreatment biopsy samples may be indicators of tumor response to therapy and patients' prognosis.…”

“…Cytokeratin immunohistochemical staining was sometimes used to count tumor buds if masked by dense inflammation but is not recommended. 5,6 The molecular basis of CRC involves several genes, including various galectins (glycan-binding proteins). Mammals currently have 16 galectins classified into 3 major families (prototypal, tandem repeat, and chimeric).…”