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.
Introduction. 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. Methods. Intraoperative samples of neoplastic tissue were collected from 195 consecutive patients who were admitted to the surgical ward for elective colorectal surgery.Results. Tumor budding parameters were positively correlated with colorectal cancer advancement, and histologic (mucinous) type of CRC. The number of tumor budding foci was lower in CRC localized in the rectum, and the number of poorly differentiated clusters was higher in younger patients. In the invasive front, a lower number of CD8 lymphocytes was found in CRC with confirmed distant metastases, and lower densities of CD3 and CD4 lymphocytes were seen in deeply invasive CRCs. The density of CD3 lymphocytes was higher in men and older patients. The number of lymphoid follicles was higher in patients with less advanced cancers. Conclusion. 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.
Colorectal cancer is a heterogenous group of neoplasms showing a variety of clinical and pathological features depending on their anatomical location. Sphingolipids are involved in the formation and progression of cancers, and their changes are an important part of the abnormalities observed during carcinogenesis. Because the course of rectal and colonic cancer differs, the aim of the study was to assess whether the sphingolipid profile is also different in tumors of these two regions. Using a combination of ultra-high-performance liquid chromatography combined with triple quadrupole mass spectrometry, differences in the amounts of cellular sphingolipids were found in colorectal cancer. Sphingosine content was higher in rectal cancer than in adjacent healthy tissue, while the content of two ceramides (C18:0-Cer and C20:0-Cer) was lower. In colon cancer, a higher content of sphingosine, sphinganine, sphingosine-1-phosphate, and two ceramides (C14:0-Cer and C24:0-Cer) was found compared to healthy tissue, but there was no decrease in the amount of any of the assessed sphingolipids. In rectal cancer, the content of sphinganine and three ceramides (C16:0-Cer, C22:0-Cer, C24:0-Cer), as well as the entire pool of ceramides, was significantly lower compared to colon cancer. The S1P/Cer ratio in rectal cancer (S1P/C18:1-Cer, S1P/C20:0-Cer, S1P/C22:0-Cer, S1P/C24:1-Cer) and in colon cancer (S1P/C18:0-Cer, S1P/C18:1-Cer, S1P/C20:0-Cer) was higher than in adjacent healthy tissue and did not differ between the two sites (rectal cancer vs. colonic cancer). It seems that the development of colorectal cancer is accompanied by complex changes in the metabolism of sphingolipids, causing not only qualitative shifts in the ceramide pool of cancer tissue but also quantitative disturbances, depending on the location of the primary tumor.
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