An index for estimating the probability of lymph node metastasis in rectal cancers. Lymph node metastasis and the histopathology of actively invasive regions of cancer

Abstract

We examined resected specimens from 40 cases of advanced rectal cancer to determine the extent of microtubular cancer nests and undifferentiated cancer cells (budding). We investigated the relationship between this budding and lymphatic invasion (ly), venous invasion (v), and lymph node metastasis (n), respectively. Moreover, we examined the relationship between ly, budding, and n in the preoperative biopsy specimens of 112 patients, including those of the 40 cases mentioned above. The degree of budding, which was abundant in the actively invasive region, showed a strong correlation with the degree of ly and the existence of n in the resected specimens. Also, budding was recognized in a relatively large portion of the biopsy specimens (52 of 112 [46.4%]) and lymph node metastasis was found in 41 of 52 specimens (78.8%). In 57 specimens, neither ly nor budding was found, and 16 of these specimens (28.1%) had positive lymph nodes. These results implied that the degree of budding in the actively invasive region can be a great help in predicting the presence of n. The presence or absence of budding in preoperative biopsy specimens also can be an important factor (along with the degree of differentiation and ly) in estimating the probability of n.

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.…”

“…A few tumor-budding studies have used vascular markers and/or elastic stains to assess vascular invasion, 11,12,19,22,26,32,37,38 but only four have analyzed the relationship between budding and vascular invasion: Kazama et al 22 found no relationship between budding and vascular invasion, whereas three other studies have reported a statistically significant correlation between budding and venous invasion, though the association was not as pronounced as the relationship with lymphatic invasion and lymph node metastases. 11,12,32 The tumor-host interaction at the invasive front may be of prognostic importance in the setting of tumor budding. Several studies have shown peritumoral lymphocytic infiltration to be an independent prognostic factor in colorectal carcinoma.…”

“…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.…”

“…The most widely cited scoring system, developed by Ueno et al, 27 defines 'high-grade budding' as 410 buds composed of fewer than 5 cells in a 25 Â field (field area ¼ 0.385 mm 2 ). Other authors have defined buds as being composed of r5 cells, 38 while some have not set an upper cell limit and instead count both single cells and bundles of five or more cells as buds, as proposed by Morodomi et al 11 and commonly applied in the Japanese literature. This heterogeneity in defining budding is compounded by the use of varying field diameters and cutoffs for defining 'high-grade' budding, especially when a score is given as #/hpf rather than/mm 2 .…”

“…Although most authors have used Ueno's definition of 'highgrade budding' (410 buds of fewer than 5 cells), all have used a 20 Â objective, rather than the 25 Â objective used by Ueno et al, resulting in significantly greater field areas than that originally reported by Ueno. Furthermore, while the majority of studies have evaluated only areas with the greatest amount of budding, others have proposed calculating an average bud count, 11 counting the number of buds along the entire invasive front 19,24,52,53 or calculating the proportion of invasive front with tumor budding. 21,36,40 Such methodological heterogeneity is illustrated in Table 1, which summarizes the bud counting methods used in a sample of tumor-budding studies.…”