Evaluation of Tumor Budding In Colorectal Adenocarcinoma

Colorectal cancer (CRC) is among the most prevalent cancers globally, with approximately one to two million new cases diagnosed each year. This makes CRC the third most common cancer and the fourth leading cause of cancer-related deaths, with 700,000 deaths per year, exceeded only by lung, liver and stomach cancers. CRC accounts for about 10% of all cancer diagnoses worldwide (Sung et al., 2021; Masetti et al., 2022) . CRC affects different races and ethnicities at various age groups in distinct ways. Among patients younger than 50 years old, the proportion of CRC is nearly double for Black individuals (16%) compared to White individuals (9%) and Hispanic individuals (6%). In Egypt, CRC ranked the seventh among cancers, following lung, breast, prostate, liver, and bladder cancers (Mounir et al., 2022). Tumor budding (TB) is characterized by the presence of individual tumor cells or small clusters of up to four cells at the invasive margin of a tumor. This histological feature, which indicates the separation of malignant cells from the main tumor mass, has intrigued pathologists since it was first identified in the 1950s (Giordano et al., 2024). Evaluating TB is crucial for improving prognostic accuracy and informing treatment decisions. Tumors with high-grade TB exhibit a significantly lower 5-year Disease-Free Survival (DFS) rate compared to those with low-grade TB. High-grade TB is regarded as a negative prognostic factor and is associated with an increased risk of recurrence (Kyong Shin et al., 2023). TB can be observed in conventional slides when prominent, but careful observation is necessary. A more thorough assessment of TB is more easily achieved if the neoplastic epithelium is highlighted using pan-cytokeratin immunostains (Mishra et al., 2022). Pan-keratin (Pan-CK) antibodies are proteins derived from cytoskeletal intermediate filaments. These antibodies are a mixture designed to detect multiple low and high molecular weight keratins. Their primary purpose is to allow for the immunohistochemical identification of all epithelial cell types, regardless of their tissue of origin, using a single diagnostic tool. In surgical pathology, Pan-CK antibodies are commonly used to confirm the epithelial origin of both neoplastic (tumorous) and non-neoplastic tissues, as well as to identify small metastases in lymph nodes. However, there are limitations to the assumption that Pan-CK antibodies will stain all epithelial tumors and that non-epithelial tissues will be "keratin negative." It has been reported that a diverse range of epithelial tumors can be Pan-CK negative, challenging the notion that these antibodies are universally applicable (Wick et al., 1986; Badzio, 2019). Pan-CK can help diagnose disease like breast cancer, lung cancer, prostate cancer, and colorectal cancer. It is often used in conjunction with other antibodies for these specific cancers (Chu and Weiss, 2002).

Sex

All

Minimum age

20 Years

Maximum age

90 Years

Inclusion Criteria:

* Specimens from patients with Colorectal Carcinoma. Tissue blocks with sufficient material. Specimens with sufficient clinical data.

Exclusion Criteria:

* Tissue blocks with insufficient, destroyed or necrotic material. Specimens with insufficient clinical data.

• RESULTWick MR, Cherwitz DL, McGlennen RC, Dehner LP. Adrenocortical carcinoma. An immunohistochemical comparison with renal cell carcinoma. Am J Pathol. 1986 Feb;122(2):343-52. PMID 2418689
• RESULTSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID 33538338
• RESULTMounir, A., Hassan, M. A., Selim, M. A., and Mahmoud, I. A. (2022). Epidemiology of Colorectal Cancer, Incidence, Survival, and Risk Factors: Cairo University Center of Oncology and Nuclear Medicine Experience. The Egyptian Journal of Hospital Medicine, 89(2), 7061-7070. https://doi.org/10.21608/ejhm.2022.272513
• RESULTMasetti M, Fallani G, Ratti F, Ferrero A, Giuliante F, Cillo U, Guglielmi A, Ettorre GM, Torzilli G, Vincenti L, Ercolani G, Cipressi C, Lombardi R, Aldrighetti L, Jovine E. Minimally invasive treatment of colorectal liver metastases: does robotic surgery provide any technical advantages over laparoscopy? A multicenter analysis from the IGoMILS (Italian Group of Minimally Invasive Liver Surgery) registry. Updates Surg. 2022 Apr;74(2):535-545. doi: 10.1007/s13304-022-01245-1. Epub 2022 Jan 31. PMID 35099776
• RESULTMishra, P. P., Madan, K., Biswas, S., Rao, A. C. K., Shetty, R., and Panda, P. (2022). Tumour budding in colorectal carcinoma: Association with other histopathological prognostic parameters. IP Archives of Cytology and Histopathology Research, 7(1), 26-31. https://doi.org/10.18231/j.achr.2022.006
• RESULTKyong Shin J, Ah Park Y, Wook Huh J, Hyeon Yun S, Cheol Kim H, Yong Lee W, Hyung Kim S, Yun Ha S, Cho YB. Is High-Grade Tumor Budding an Independent Prognostic Factor in Stage II Colon Cancer? Dis Colon Rectum. 2023 Aug 1;66(8):e801-e808. doi: 10.1097/DCR.0000000000002345. Epub 2022 Apr 5. PMID 35394982
• Giordano PG, Diaz Zelaya AG, Aguilera Molina YY, Taboada Mostajo NO, Ajete Ramos Y, Ortega Garcia R, Peralta de Michelis E, Meneu Diaz JC. Clinico-pathological evaluation of tumor budding in the oncological progression of colorectal cancer. Med Clin (Barc). 2024 Aug 30;163(4):159-166. doi: 10.1016/j.medcli.2024.02.017. Epub 2024 May 1. English, Spanish.