Tumour budding in solid cancers

Lugli, Alessandro; Zlobec, Inti; Berger, Martin D.; Kirsch, Richard; Nagtegaal, Irıs D.

doi:10.1038/s41571-020-0422-y

Cited by 235 publications

(304 citation statements)

References 188 publications

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“…Some reports in adenocarcinomas (i.e., not signet ring cell histology) suggest the number of buds can range from zero to several hundred depending on the objective lens area [4]. Although it can be argued that a very large amount of tumor buds per defined area may be the result of cutting artifact, the absence of tumor buds along the entire border of the cancer can be explained by either [1] buds were overseen during diagnosis or [2] it is the result of a true pattern of tumor growth, or [3] in the case of pT1, tissues rather represented pseudoinvasion, which is excluded here, after careful re-examination of pT1 BD0. The reason for this growth pattern cannot solely be explained by the presence of peritumoral lymphocytic inflammation, which is described in our study by a high Klintrup-Mäkinen score, with values of 3 indicating thick bands of inflammatory infiltrates around the invasion edge of the cancer [3].…”

Section: Discussionmentioning

confidence: 99%

“…Tumor budding is an important prognostic factor in the clinical management of cancer patients [1]. Although best described in colorectal cancers, evidence indicates that patients with a variety of different tumor types suffer from more aggressive disease and worse overall and disease-free survival in the context of high-grade tumor budding [1]. The definition of "high-grade" may vary depending on the clinical endpoint of interest.…”

Section: Introductionmentioning

confidence: 99%

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Refining the ITBCC tumor budding scoring system with a “zero-budding” category in colorectal cancer

et al. 2021

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Tumor budding scoring guidelines from the International Tumor Budding Consensus Conference (ITBCC) for colorectal cancer propose three groups: BD1 (0–4 buds/0.785 mm2), BD2 (5–9 buds/0.785 mm2), and BD3 (10 or more buds/0.785 mm2). Here, we investigate whether a fourth scoring category, namely zero buds, may have additional clinical relevance. The number of tumor buds/0.785 mm2 was scored in 959 cases. Those with zero tumor buds were considered BD0, while a new BD1 category of 1–4 buds was proposed. Associations of both scoring approaches with clinicopathological features were analyzed. Conventional ITBCC scoring showed expected associations with unfavorable histopathological prognostic factors. In total, 111/959 (11.6%) were BD0. A significant difference was found when BD0 was compared statistically to BD1 (1–4 buds) for pT, TNM, tumor grade, and lymphatic, venous, and perineural invasion (p < 0.01, all). Tumors with BD0 occur relatively frequently and contribute additional information on tumor behavior. BD0 should be considered for subsequent ITBCC guidelines.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Refining the ITBCC tumor budding scoring system with a “zero-budding” category in colorectal cancer

et al. 2021

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“…The environmental factors contributing to CRC development include diet, obesity, infection, tobacco use and alcohol consumption [7]. Sporadic CRC originates in differentiated intestinal epithelial cells, which then undergo a remarkable phenotypic plasticity during tumor progression, resulting in acquisition of a highly invasive, metastatic cell phenotype [8,9]. While rates of cure for the early stage disease may be above 90%, for the locally advanced and metastatic disease, 5-year survival is dismal, and may be as low as 15% [3].…”

Section: Introductionmentioning

confidence: 99%

Myosin Motors: Novel Regulators and Therapeutic Targets in Colorectal Cancer

Naydenov

Lechuga

Huang

et al. 2021

Cancers

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Colorectal cancer (CRC) remains the third most common cause of cancer and the second most common cause of cancer deaths worldwide. Clinicians are largely faced with advanced and metastatic disease for which few interventions are available. One poorly understood aspect of CRC involves altered organization of the actin cytoskeleton, especially at the metastatic stage of the disease. Myosin motors are crucial regulators of actin cytoskeletal architecture and remodeling. They act as mechanosensors of the tumor environments and control key cellular processes linked to oncogenesis, including cell division, extracellular matrix adhesion and tissue invasion. Different myosins play either oncogenic or tumor suppressor roles in breast, lung and prostate cancer; however, little is known about their functions in CRC. This review focuses on the functional roles of myosins in colon cancer development. We discuss the most studied class of myosins, class II (conventional) myosins, as well as several classes (I, V, VI, X and XVIII) of unconventional myosins that have been linked to CRC development. Altered expression and mutations of these motors in clinical tumor samples and their roles in CRC growth and metastasis are described. We also evaluate the potential of using small molecular modulators of myosin activity to develop novel anticancer therapies.

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“…As a putative depiction of the initial steps of the metastatic cascade, presence of tumor budding has been found to be of prognostic significance in various cancers, including carcinomas of gastrointestinal origin, lung cancer, head and neck carcinomas, and breast cancer [ 8 , 25 , 26 , 27 ]. Colorectal cancers are the type of primary cancers where tumor budding was initially studied and remain the best studied locations [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Role of Tumor Budding in Breast Cancer Patients Receiving Neo-Adjuvant Therapy

Mozarowski

Rasaiah

Reed

et al. 2021

JCM

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Background: Isolated tumor cells or small clusters of tumor cells observed in the vicinity of the main tumor mass in pathology sections, termed tumor budding, are common in cancers and have been associated with prognosis in some settings. This study examined the clinical associations and treatment efficacy implications of tumor budding in breast cancer patients receiving neo-adjuvant therapy. Methods: Breast cancer patients that received neo-adjuvant therapy before definitive surgical treatment in a single cancer center over a 7-year period were included, and their records were reviewed. Data extracted included patient demographics, tumor characteristics and pathologic response to treatment at surgery. The initial breast cancer biopsy before any therapy was reviewed by two pathologists, and a hot spot area was evaluated for tumor budding (defined as 1 to 5 cancer cells observed detached from the main tumor mass). Results: Seventy-five patients who received neo-adjuvant therapy (73 received chemotherapy and 2 received hormonal therapy) were included. Tumor budding was observed in two-thirds of the patients. There were no significant differences in patient (age and menopause status) and tumor (stage, histology and molecular sub-type equivalent) characteristics between the group that had tumor budding and the group that did not have tumor budding in the pre-treatment biopsy. Likewise, no statistically significant differences were observed in the frequency of complete or partial responses between the two groups. Conclusion: In this cohort of breast cancer patients receiving neo-adjuvant therapy, tumor budding was frequent, but it was not associated with tumor characteristics or pathologic responses to treatment. The value of tumor budding as a prognostic factor in the neo-adjuvant setting within the general breast cancer population could not be confirmed, but such a value in specific sub-groups deserves further investigation, given the pathophysiologic rationale and data from other settings.

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Tumour budding in solid cancers

Cited by 235 publications

References 188 publications

Refining the ITBCC tumor budding scoring system with a “zero-budding” category in colorectal cancer

Refining the ITBCC tumor budding scoring system with a “zero-budding” category in colorectal cancer

Myosin Motors: Novel Regulators and Therapeutic Targets in Colorectal Cancer

Prognostic Role of Tumor Budding in Breast Cancer Patients Receiving Neo-Adjuvant Therapy

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