Intensity of Tumor Budding as an Index for the Malignant Potential in Invasive Rectal Carcinoma

Abstract

Purpose: The aim of this study was to quantitatively assess the intensity of tumor budding in rectal carcinoma and to determine how it correlates with the malignant potential.Materials and Methods: Intensities of the tumor budding at the invasive front of the surgical specimens from 90 patients (male, 51) with well-or moderately-differentiated rectal carcinoma were investigated. Differences in the budding intensity among pathologic variables were compared, and recurrences and survivals were analyzed in accordance with degree of the budding intensity. The patients ranged in age from 33 to 75 years (mean, 55.4) with the median follow-up being 43 months (range, 12～ 108).Results: Tumor budding was identified in 89 patients (98.9%) with a mean intensity of 7.5±5.3. The budding intensity was significantly higher in tumors with lymphatic invasion (p=0.0081), blood vessel invasion (p＜ 0.0001), and perineural invasion (p=0.0013) than in those tumor without these findings. It became significantly higher with the increase in nodal stage (p＜0.0001). The intensity of tumor budding in patients with relapse (29 patients) was significantly higher than that in patients without relapse (6.2±5.0 vs. 10.2±4.9; p=0.0005), but this difference in the intensity was observed only for the node-positive patients (8.0±3.4 vs. 11.9±5.1; p=0.0064). W hen the patients were stratified into two groups on either side of the mean of the intensity, the higher intensity group showed a significantly less favorable diseasefree (DFS) and overall survival (OS) (p=0.0026 and 0.0205, respectively). Based on the multivariate analysis, the nodal stage and the intensity of budding proved to be the independent variables associated with DFS (p=0.023 and 0.03, respectively).Conclusion: Tumor budding at the invasive margin is a reliable pathologic index that indicates a higher malignant potential and a less favorable prognosis for patients with advanced rectal carcinoma. (Cancer Res Treat. 2005; 37:177-182)

Tumor Budding in Colorectal Carcinoma

“…Two studies did not specify the microscope field area covered by the high power objective, further limiting comparison with other data [31, 34]. Of the two studies using routine sections [28, 37], the study by Sy et al, utilized a cutoff of >9 buds in a 20× objective field [37], but they did not identify a worse survival on multivariate analysis in cases with high budding across their entire population, which contrasts with our data and that of several other studies [2, 6, 7, 17, 18, 23, 24, 28]. Choi and colleagues [28] found >10 buds in a 20× field to be the appropriate cutoff for high budding in a series of 244 rectal tumors, although they used a semiquantitative approach [28].…”

“…In six of the previously mentioned studies [6, 17, 19, 21, 24, 25], the study group was restricted to a specific T stage and each of these studies used a different evaluation method, including five which employed immunohistochemistry instead of routine H&E stains. In two of the five remaining studies, the definition of a tumor bud was not specified [2, 20] and two others used two different methods of tumor bud assessment [18, 22]. While each of these studies found tumor budding to be of prognostic significance, only the study by Ueno et al [23] included a large number of cases across various T stages, used only H&E-stained sections and used a specific definition of a tumor bud.…”

“…We believe that the approach outlined by Mitrovic et al (20) and used here, helps to mitigate some of these issues. We used a commonly accepted definition of a tumor bud [18, 19, 21, 23–25] and employed a simple bud evaluation method which is likely to be reproducible in routine practice to confirm the robust prognostic significance of tumor budding. Our data show good reproducibility with strong agreement between six reviewers including four general surgical pathologists (weighted kappa 0.70 and 0.72).…”

Tumor budding in colorectal carcinoma: time to take notice

“…There is a strong association between budding and the presence of lymph node metastases and lymphovascular invasion, 11,12,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] defined by the presence of tumor cells within an endothelium-lined space, and it has been suggested that buds represent the part of the tumor that has gained the ability to invade lymphatics and vascular channels. This idea is supported by two intriguing morphological studies: Morodomi et al 33 examined serial sections of high-budding areas to demonstrate that budding nests are often found adjacent to areas of lymphovascular space invasion, and, in a more recent study, Ohtsuki et al 31 performed double staining for anti-cytokeratin antibodies and anti-lymphatic antibodies, finding that a number of 'buds' at the invasive edge of a tumor are in fact located in small lymphatic spaces.…”

“…11,12,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] On multivariate analysis, budding has consistently emerged as an independent adverse prognostic factor, associated with local tumor recurrence and distant metastases, and significantly worse overall and disease-free survival. 12,15,16,21,27,28,31,32,[34][35][36]38,40,41 The adverse prognostic impact of high-grade tumor budding is seen in both early and advanced colorectal carcinoma, and there are several scenarios in which this feature might influence clinical decision making, particularly in early colorectal carcinoma.…”