The role of tumoral stroma in determining the forecast of recurrence and fatal consequence of stage IIA-IIIB colorectal cancer
Colorectal cancer (CRC) ranks 2nd in the structure of mortality from malignant neoplasms (MN). One of the criteria for the prognosis of CRC may be a tumor stroma, which has not been widely used in clinical practice.
The aim was to determine the main morphological features of the stroma CRC T3N0-2M0 and search for prognostic criteria for their recurrence and lethal outcome according to the operating material and autopsy.
Materials and methods. Group I included primary CRC without recurrence. The average recurrence-free period was 5 years (62.5±16.5 months). Group II – primary CRC with recurrence; IIA – with recurrences within 5 years from the date of tumor removal that did not lead to death; IIB – with the appearance of recurrence and lethal consequence of the generalization of the tumor process within 5 years from the moment of removal of the primary tumor. CRC micropreparations made according to the standard method with G + E staining were studied; immunohistochemical study was performed using monoclonal antibodies to smooth muscle actin alpha.
Results. Stromal-parenchymal ratio >50 % is a prognostic criterion for recurrence (p<0.05) and shorter recurrence-free survival (p<0.001) of patients with stage IIA-IIIB CRC. Immature stroma type CRC stage IIA-IIIB is associated with the presence of tumor budding (p<0.001), G3 differentiation (p<0.01), shorter recurrence-free survival (p<0.001); among recurrent CRCs, the immature type of stroma is associated with the lethal outcome of patients (p<0.05). Expressed levels of tumor-activated fibroblasts are one of the criteria for immature CRC stroma (p<0.003), but as an independent prognostic criterion has limited prognostic value.
Conclusions. TSR and immature type of stroma are prognostic criteria for recurrence and recurrence period of CRC pT3N0-2M0, more typical of tumors of patients with recurrence and lethal outcome with the same ratio of tumors by differentiation.
Fedorenko, Z. P., Hulak, L. O., Mykhaillvych, Yu. Y., Horokh, Ye. L., Ryzhov, A. Yu., Sumkina, O. V., Kutsenko, L. B. (2020). Rak v Ukraini, 2018–2019. Zakhvoriuvanist, smertnist, pokaznyky diialnosti onkolohichnoi sluzhby. Biuleten natsionalnoho kantser-reiestru Ukrainy, 21, 101.
Ryuk, J. P., Choi, G.-S., Park, J. S., Kim, H. J., Park, S. Y., Yoon, G. S. et. al. (2014). Predictive factors and the prognosis of recurrence of colorectal cancer within 2 years after curative resection. Annals of Surgical Treatment and Research, 86 (3), 143–151. doi: http://doi.org/10.4174/astr.2014.86.3.143
Poornakala, S., Prema, N. (2019). A study of morphological prognostic factors in colorectal cancer and survival analysis. Indian Journal of Pathology and Microbiology, 62 (1), 36. doi: http://doi.org/10.4103/ijpm.ijpm_91_18
Conklin, M. W., Keely, P. J. (2012). Why the stroma matters in breast cancer: insights into breast cancer patient outcomes through the examination of stromal biomarkers. Cell Adhesion & Migration, 6 (3), 249–260. doi: http://doi.org/10.4161/cam.20567
Ueno, H., Jones, A. M., Wilkinson, K. H., Jass, J. R., Talbot, I. C. (2004). Histological categorisation of fibrotic cancer stroma in advanced rectal cancer. Gut, 53 (4), 581–586. doi: http://doi.org/10.1136/gut.2003.028365
Hutchins, G. G. A., Treanor, D., Wright, A., Handley, K., Magill, L. et. al. (2017). Intratumoral stromal morphometry predicts disease recurrence but not response to 5-fluorouracil-results from the QUASAR trial of colorectal cancer. Histopathology, 72 (3), 391–404. doi: http://doi.org/10.1111/his.13326
Hynes, S. O., Coleman, H. G., Kelly, P. J., Irwin, S., O’Neill, R. F., Gray, R. T. et. al. (2017). Back to the future: routine morphological assessment of the tumour microenvironment is prognostic in stage II/III colon cancer in a large population-based study. Histopathology, 71 (1), 12–26. doi: http://doi.org/10.1111/his.13181
Huijbers, A., Tollenaar, R. A. E. M., v Pelt, G. W., Zeestraten, E. C. M., Dutton, S., McConkey, C. C. et. al. (2013). The proportion of tumor-stroma as a strong prognosticator for stage II and III colon cancer patients: validation in the VICTOR trial. Annals of Oncology, 24 (1), 179–185. doi: http://doi.org/10.1093/annonc/mds246
Eriksen, A. C., Sørensen, F. B., Lindebjerg, J., Hager, H., dePont Christensen, R., Kjær-Frifeldt, S., Hansen, T. F. (2018). The prognostic value of tumour stroma ratio and tumour budding in stage II colon cancer. A nationwide population-based study. International Journal of Colorectal Disease, 33 (8), 1115–1124. doi: http://doi.org/10.1007/s00384-018-3076-9
Martin, M., Pujuguet, P., Martin, F. (1996). Role of Stromal Myofibroblasts Infiltrating Colon Cancer in Tumor Invasion. Pathology – Research and Practice, 192 (7), 712–717. doi: http://doi.org/10.1016/s0344-0338(96)80093-8
Mao, Y., Keller, E. T., Garfield, D. H., Shen, K., Wang, J. (2012). Stromal cells in tumor microenvironment and breast cancer. Cancer and Metastasis Reviews, 32 (1-2), 303–315. doi: http://doi.org/10.1007/s10555-012-9415-3
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