Simultaneous analysis of tumor-infiltrating immune cells density, tumor budding status, and presence of lymphoid follicles in CRC tissue

Abstract

Colorectal cancer (CRC) affects more than 1,000,000 people worldwide each year. Recently, the number of young patients with early-onset colorectal cancer has increased, and right-sided colorectal cancer is still often diagnosed only in advanced stages. The TNM classification is not perfect for CRC staging. This study aimed to perform, for the first time, simultaneous analysis of tumor-infiltrating immune cell density, presence of lymphoid follicles, and budding status in CRC tissue. Intraoperative samples of neoplastic tissue were collected from 195 consecutive patients who were admitted to the surgical ward for elective colorectal surgery. Histological parameters were assessed in the tissue samples: tumor budding foci, poorly differentiated clusters and areas of poorly differentiated components. Tumor-infiltrating immune cells (tumor-associated neutrophils and tumor-infiltrating lymphocytes) were detected in five randomly chosen, areas at the tumor center and at the invasive front. Additionally, the presence of lymphoid follicles in CRC tissue was assessed. Tumor budding parameters were positively correlated with colorectal cancer advancement or histologic (mucinous) type of CRC. The number of poorly differentiated clusters was higher in younger patients. Lower densities of CD3 and CD4 lymphocytes were seen in CRC with a greater depth of tumor invasion. Lower densities of CD3 and CD8 lymphocytes were found in CRC with metastases to the surrounding lymph nodes. The lower density of CD8 lymphocytes was observed in CRC with distant metastases. Lower densities of tumor-associated neutrophils and tumor-infiltrating lymphocytes (CD3 and CD8) were revealed in CRC without lymphoid follicles. The number of lymphoid follicles was higher in patients with less advanced CRCs. Three histopathology markers, such as high tumor budding, scanty lymphocyte infiltration, and the poverty of lymphoid follicles, complement each other, appear to be reliable indicators of colorectal cancer progression, and could be useful in everyday medical practice, but their widespread use requires further research. We propose to take into account these markers, in the assessment of colorectal cancer advancement, in addition to the TNM classification.

Multi-omics pan-cancer study of SPTBN2 and its value as a potential therapeutic target in pancreatic cancer

“…As an integral part of the TME, tumor-infiltrating immune cells play a crucial role in tumor progression and development 24 – 26 . We performed a single-cell analysis and found that SPTBN2 is significantly enriched in PAAD tumor cells (Fig.…”

Relationship between Preoperative Pyuria and Bacille Calmette-Guerin Treatment in Intravesical Recurrence after Transurethral Resection of High-Risk, Non-Muscle Invasive, Bladder Carcinoma: A Retrospective Study of Human Data

“…Most malignant tumors have significant leucocytic infiltrates and these have been linked to a poor prognosis [ 33 , 34 ]. In colorectal cancer, abundant tumor budding, scanty lymphocyte infiltration, and few lymphoid follicles tend to coexist and appear to be reliable prognostic indicators [ 35 ]. Leucocyte infiltrates are attracted to tumors by chemotactic factors released by viable or necrotic tumor cells or by cells within the tumor stroma [ 36 ].…”

Diverse Sphingolipid Profiles in Rectal and Colon Cancer

“…However, data on ceramide metabolism in CRC are still ambiguous and their mechanism has not been confirmed without doubt. In CRC, one study showed a higher content (compared to healthy adjacent tissue) of both S1P and several ceramide species [ 2 ].…”

“…In addition to tumor grading and staging, some genetic, biochemical, and histological markers have been used for the prognostication and optimization of adjuvant treatment [ 2 , 3 ], but there is no consensus on their exact role in RC patients. The accumulation of sphingolipids (SL) accounts for almost 90% of the changes in the colon cancer cell line [ 4 ].…”

“…Cer are bioactive lipids that consist of a sphingoid base (one of several) and a fatty acyl chain of various lengths and a varied degree of saturation. To date, more than 200 structurally distinct molecular Cer species have been described in mammalian cells, with different biological properties depending on the chemical structure [ 2 ]. Cer are relevant components of cell membranes, and in response to stress stimuli, they undergo rapid turnover, which firmly changes their biophysical properties.…”