Number Of Tumor Buds Research Articles

The Relationship Between Tumor Budding and Patient's Survival in Breast Cancer.

Breast cancer is a severe life-threatening condition in which many women are involved yearly. One factor that has recently been noticed and investigated as a diagnostic predictor of this type of cancer is the number of tumor buds and the relation of this factor with a patient's survival rate. This study includes 150 female patients over 18 years old with a mean age of 53.99 ± 12.56 years old with breast cancer, which was diagnosed at various medical centers, including Rouhani Hospital itself, and referred to Rouhani Hospital Medical Center, Babol, Iran. The number of intratumoral and peritumoral buds in patients' microscopic slides were archived and evaluated along with tumor microenvironment on hematoxylin and eosin (H&E) slides and compared to other clinicopathological findings. This article precisely investigated the relationship between the number of intratumoral and peritumoral buds with patients' 5-year survival rate. Also, the relationship between age, tumor stage, grade, size, the number of lymph nodes involved, and the presence of metastasis with the number of intratumoral and peritumoral buds was studied. The result showed a significant statistical association between the number of intratumoral and peritumoral buds with tumor size, tumor stage, presence of metastasis, the number of lymph nodes involved, and 5-year survival rate. On the other hand, there is not a significant statistical association between the number of intratumoral and peritumoral buds with age and tumor grade. Our investigation revealed a significant statistical relationship between the number of tumor buds and patients' survival rate. So, this factor should be considered significant to help those patients increase their survival ratio.

Histomorphological Evaluation of Desmoplastic Tumor Stroma in Malignant Ovarian Surface Epithelial Tumors.

Ovarian cancer is the 8th most common cancer in women worldwide. Tumor budding is defined as a type of invasive growth in carcinomas with either a single tumor cell or a cluster of up to four cells at the invasive tumor front and is associated with epithelial-mesenchymal transition. A reactive stroma rich in cancer-associated fibroblasts is associated with higher tumor grade and poorer prognosis in breast, colorectal, and oral cancers. The present study was conducted to highlight the prognostic significance of tumor budding and fibrotic cancer stroma in malignant ovarian surface epithelial tumors with known prognostic parameters. This was a retrospective cross-sectional study conducted over a 2-year period, in which all histologically diagnosed cases of malignant ovarian surface epithelial tumors who underwent surgery were included. The fibrotic stroma was classified into three distinct categories - mature, intermediate, and immature. The number of tumor buds was counted at the invasive front of the tumor and graded based on the number of buds - 0-5, 5-9, and ≥10 buds. Among the 50 cases, 32% (16 cases) had mature stroma, whereas 30% (15 cases) and 38% (19 cases) had intermediate and immature stroma, respectively. Although a significant association could not be established between tumor budding and stroma grade, a fair agreement was established between them. A significant association could be established between histological grade with both tumor budding (P = 0.03) and fibrotic stroma grade (P = 0.02). The study highlighted the role of stromal response in malignant surface epithelial tumors of the ovary since a higher-grade tumor was associated with an immature stroma, whereas a lower-grade tumor was associated with a mature stroma.

Composite scoring system and optimal tumor budding cut-off number for estimating lymph node metastasis in submucosal colorectal cancer

BackgroundTumor budding is associated with lymph node (LN) metastasis in submucosal colorectal cancer (CRC). However, the rate of LN metastasis associated with the number of tumor buds is unknown. Here, we determined the optimal tumor budding cut-off number and developed a composite scoring system (CSS) for estimating LN metastasis of submucosal CRC.MethodsIn total, 395 patients with histologically confirmed T1N0–2M0 CRC were evaluated. The clinicopathological characteristics were subjected to univariate and multivariate analyses. The Akaike information criterion (AIC) values of the multivariate models were evaluated to identify the optimal cut-off number. A CSS for LN metastasis was developed using independent risk factors.ResultsThe prevalence of LN metastasis was 13.2%. Histological differentiation, lymphatic or venous invasion, and tumor budding were associated with LN metastasis in univariate analyses. In multivariate models adjusted for histological differentiation and lymphatic or venous invasion, the AIC value was lowest for five tumor buds. Unfavorable differentiation (odds ratio [OR], 8.16; 95% confidence interval [CI], 1.80–36.89), lymphatic or venous invasion (OR, 5.91; 95% CI, 2.91–11.97), and five or more tumor buds (OR, 3.01; 95% CI, 1.21–7.69) were independent risk factors. In a CSS using these three risk factors, the rates of LN metastasis were 5.6%, 15.5%, 31.0%, and 52.4% for total composite scores of 0, 1, 2, and ≥ 3, respectively.ConclusionsFor the estimation of LN metastasis in submucosal CRC, the optimal tumor budding cut-off number was five. Our CSS can be utilized to estimate LN metastasis.

Impact of tumour budding grade in 310 patients who underwent surgical resection for extrahepatic cholangiocarcinoma.

Tumour budding is a risk factor for poor prognosis in various cancers. Tumour buds may present an epithelial-mesenchymal transition (EMT) morphological phenotype. This study aimed to elucidate the prognostic impact of tumour budding grade and its association with clinicopathological and EMT-related features in perihilar cholangiocarcinoma (PHCC) or distal cholangiocarcinoma (DCC). Subjects included 195 PHCC and 115 DCC patients. The numbers of tumour buds in different patients were stratified for postoperative survival using the recursive partitioning technique. Consequently, the numbers of tumour buds in PHCC patients were classified into three grades; namely, low (0-4 buds); intermediate (5-11 buds); and high (≥12 buds); those of DCC patients were classified into two grades; namely, low (0-4 buds) and high (≥5 buds). In both PHCC and DCC patients, high tumour budding grade was associated with poor histological differentiation, higher pT factor, presence of lymphatic, venous, perineural invasion and regional lymph node metastasis. In PHCC patients, residual invasive tumour in the resected margin was also associated with high tumour budding grade. For both PHCC and DCC patients, high tumour budding grade was an independent adverse prognostic factor in multivariate analysis (P<0001 and P=0.046, respectively). Immunohistochemical examination revealed that the number of tumour buds increased in patients with tumours showing a mesenchymal profile (negative for E-cadherin and positive for vimentin). Higher tumour budding grade is associated with invasive clinicopathological features, adverse postoperative prognosis and EMT status in extrahepatic cholangiocarcinoma.

Automatic evaluation of tumor budding in immunohistochemically stained colorectal carcinomas and correlation to clinical outcome

BackgroundTumor budding, meaning a detachment of tumor cells at the invasion front of colorectal carcinoma (CRC) into single cells or clusters (<=5 tumor cells), has been shown to correlate to an inferior clinical outcome by several independent studies. Therefore, it has been discussed as a complementary prognostic factor to the TNM staging system, and it is already included in national guidelines as an additional prognostic parameter. However, its application by manual evaluation in routine pathology is hampered due to the use of several slightly different assessment systems, a time-consuming manual counting process and a high inter-observer variability. Hence, we established and validated an automatic image processing approach to reliably quantify tumor budding in immunohistochemically (IHC) stained sections of CRC samples.MethodsThis approach combines classical segmentation methods (like morphological operations) and machine learning techniques (k-means and hierarchical clustering, convolutional neural networks) to reliably detect tumor buds in colorectal carcinoma samples immunohistochemically stained for pan-cytokeratin. As a possible application, we tested it on whole-slide images as well as on tissue microarrays (TMA) from a clinically well-annotated CRC cohort.ResultsOur automatic tumor budding evaluation tool detected the absolute number of tumor buds per image with a very good correlation to the manually segmented ground truth (R2 value of 0.86).Furthermore the automatic evaluation of whole-slide images from 20 CRC-patients, we found that neither the detected number of tumor buds at the invasion front nor the number in hotspots was associated with the nodal status. However, the number of spatial clusters of tumor buds (budding hotspots) significantly correlated to the nodal status (p-value = 0.003 for N0 vs. N1/N2). TMAs were not feasible for tumor budding evaluation, as the spatial relationship of tumor buds (especially hotspots) was not preserved.ConclusionsAutomatic image processing is a feasible and valid assessment tool for tumor budding in CRC on whole-slide images. Interestingly, only the spatial clustering of the tumor buds in hotspots (and especially the number of hotspots) and not the absolute number of tumor buds showed a clinically relevant correlation with patient outcome in our data.

Tumour buds determine prognosis in resected pancreatic ductal adenocarcinoma

BackgroundThe prognostic effect of tumour budding was retrospectively analysed in a cohort of 173 patients with resected pancreatic ductal adenocarcinomas (PDACs) of the prospective clinical multicentre CONKO-001 trial.MethodsHaematoxylin and eosin (H&E)-stained whole tissue slides were evaluated. In two independent approaches, the mean number of tumour buds was analysed according to the consensus criteria in colorectal cancer, in one 0.785 mm2 field of view and additionally in 10 high-power fields (HPF) (HPF = 0.238 mm2).ResultsTumour budding was significantly associated with a higher tumour grade (p < 0.001) but not with distant or lymph node metastasis. Regardless of the quantification approach, an increased number of tumour buds was significantly associated with reduced disease-free survival (DFS) and overall survival (OS) (10 HPF approach DFS: HR = 1.056 (95% CI 1.022–1.092), p = 0.001; OS: HR = 1.052 (95% CI 1.018–1.087), p = 0.002; consensus method DFS: HR = 1.037 (95% CI 1.017–1.058), p < 0.001; OS: HR = 1.040 (95% CI 1.019–1.061), p < 0.001). Recently published cut-offs for tumour budding in colorectal cancer were prognostic in PDAC as well.ConclusionsTumour budding is prognostic in the CONKO-001 clinical cohort of patients. Further standardisation and validation in additional clinical cohorts are necessary.

Systematic assessment of intra- and peri-metastatic tumor budding in patients with stage IV colorectal cancer.

626 Background: Tumor budding is a strong independent prognostic factor in primary colorectal cancer (CRC). The prognosis of stage IV CRC is still poor and there is need for biomarkers to facilitate the clinical management. Data on tumor budding in colorectal cancer distant metastases (CRDM) are still missing. Therefore, the aim of this study was to analyze its role in tumor progression. Methods: 73 stage IV CRC with clinico-pathological data were retrieved from a cohort of 331 CRC patients, surgically treated between 2002 and 2013 at the University Hospital of Bern. Tumor budding was visualized immunohistochemically by pan-cytokeratin staining. Tumor budding was defined as intra- and peri-tumoral budding in the primary tumor (ITB = buds in the tumor center; PTB = buds at the tumor margin), intra- and perinodal budding (INB and PNB) and intra- and peri-metastatic tumor budding (IMB and PMB). Overall tumor budding was defined as tumor buds independent of the center and margin (OTB, ONB, OMB). The tumor bud count was assessed by calculating the mean number of tumor buds in 10 high power fields. For survival analysis a cut off of 10 tumor buds was applied to subdivide the tumors with low and high numbers of tumor buds. Results: In lymph nodes and CRDM, the tumor bud count was lower compared to primary tumors (PNB: 13; INB: 18; ONB: 21 vs PMB: 10; IMB: 21; OMB: 22 vs PTB: 23; ITB: 24; OTB: 33). For PTB/PNB and OTB/ONB, there were significant differences between primary tumor and lymph node metastasis (PTB/PNB: p &lt; 0.001; OTB/ONB: 0.008) and primary tumor and distant metastases (PTB/PMB: p &lt; 0.001; OTB/OMB: 0.007). The presence of PMB was predicted by INB, PNB and V1 (p = 0.032, p = 0.001 and p = 0.003). A trend towards a worse prognosis in patients with a high OMB number was observed. Conclusions: Tumor budding is present in lymph node and distant metastases of CRC, but its number is lower compared to the corresponding primary tumor. As tumor budding in local and distant metastases seems to be a predictor of tumor progression, these novel data should be considered as a basis for further analysis in large and multicentric clinical trials.

Tumor Budding in Breast Carcinoma: Relation to E-Cadherin, MMP-9 Expression, and Metastasis Risk

Background: Tumor budding is a histopathologic entity refers to small cluster of cancer cells at the invasive edge of tumor. It was assumed that tumor budding is linked to epithelial-mesenchymal transition, an early event in metastasis. Objective: This study aimed to find out the correlation of tumor budding with E-cadherin and MMP-9 expression and risk of metastasis in breast carcinoma. Method: We investigated 35 cases breast carcinoma with metastasis and 35 cases without metastasis. The number of tumor budding was counted in cytokeratin-stained slides with 400x magnification (0.57 mm2). Result: Cut-off point by ROC analysis was 11 and the patient was categorized into low grade (0-10 buds) and high grade (11 or more buds) tumor budding. Inter-observer agreement was good with K value 0.914. Low level of E-cadherin was not significantly correlated with high grade tumor budding (p=0.660), meanwhile high level of MMP-9 was significantly correlated with high grade tumor budding (p=0.001). High grade tumor budding was a significant, independent risk factor of metastasis in breast carcinoma (OR=38.2, 95% CI 7.5-193.7, p<0.001). Conclusion: In conclusion, tumor budding grade is related to level of MMP-9 but has no correlation E-cadherin expression. High grade tumor budding is an independent risk factor of metastasis in breast carcinoma. Keywords: Tumor budding, E-cadherin, MMP-9, metastasis, breast carcinoma.

The relationship between tumour budding, the tumour microenvironment and survival in patients with primary operable colorectal cancer.

Background:Tumour budding has been reported to reflect invasiveness, metastasis and unfavourable prognosis in colorectal cancer. The aim of the study was to examine the relationship between tumour budding and clinicopathological characteristics, tumour microenvironment and survival in patients with primary operable colorectal cancer.Methods:A total of 303 patients from a prospective data set of patients with primary operable colorectal cancer were included in the study. The presence of budding was determined through assessment of all tumour-containing H&E slides and the number of tumour buds was counted using a 10 high-powered field method. Routine pathologic sections were used to assess: tumour necrosis, the tumour inflammatory cell infiltrate using Klintrup–Makinen (KM) grade and tumour stroma percentage (TSP) combined as the Glasgow Microenvironment Score (GMS).Results:High-grade tumour budding was present in 39% of all tumours and in 28% of node-negative tumours respectively. High-grade budding was significantly associated with T stage (P<0.001), N stage (P<0.001), TNM stage (P<0.001), serosal involvement (P<0.001), venous invasion (P<0.005), KM grade (P=0.022), high tumour stroma (P<0.001) and GMS (P<0.001). Tumour budding was associated with reduced cancer-specific survival (CSS) (HR=4.03; 95% confidence interval (CI), 2.50–6.52; P<0.001), independent of age (HR=1.47; 95% CI, 1.13–1.90; P=0.004), TNM stage (HR=1.52; 95% CI, 1.02–2.25; P=0.040), venous invasion (HR=1.73; 95% CI, 1.13–2.64; P=0.012) and GMS (HR=1.54; 95% CI, 1.15–2.07; P=0.004).Conclusions:The presence of tumour budding was associated with elements of the tumour microenvironment and was an independent adverse prognostic factor in patients with primary operable colorectal cancer. Specifically high tumour budding stratifies effectively the prognostic value of tumour stage, venous invasion and GMS. Taken together, tumour budding should be assessed routinely in patients with primary operable colorectal cancer.

Correlation of number of tumor buds and tumor stage in large bowel carcinomas

Correlation of number of tumor buds and tumor stage in large bowel carcinomas

Molecular profiling of tumour budding implicates TGFβ-mediated epithelial-mesenchymal transition as a therapeutic target in oral squamous cell carcinoma.

Although tumour budding is an adverse prognostic factor for many cancer types, the molecular mechanisms governing this phenomenon are incompletely understood. Therefore, understanding the molecular basis of tumour budding may provide new therapeutic and diagnostic options. We employ digital image analysis to demonstrate that the number of tumour buds in cytokeratin-stained sections correlates with patients having lymph node metastases at diagnosis. The tumour bud count was also a predictor of overall survival, independent of TNM stage. Tumour buds and paired central tumour areas were subsequently collected from oral squamous cell carcinoma (OSCC) specimens, using laser capture microdissection, and examined with RNA sequencing and miRNA-qPCR arrays. Compared with cells from the central parts of the tumours, budding cells exhibited a particular gene expression signature, comprising factors involved in epithelial-mesenchymal transition (EMT) and activated TGFβ signalling. Transcription factors ZEB1 and PRRX1 were up-regulated concomitantly with the decreased expression of mesenchymal-epithelial (MET) transcription factors (eg OVOL1) in addition to Krüppel-like factors and Grainyhead-like factors. Moreover, miR-200 family members were down-regulated in budding tumour cells. We used immunohistochemistry to validate five markers of the EMT/MET process in 199 OSCC tumours, as well as in situ hybridization in 20 OSCC samples. Given the strong relationship between tumour budding and the development of lymph node metastases and an adverse prognosis, therapeutics based on inhibiting the activation of TGFβ signalling may prove useful in the treatment of OSCC.

Subcutaneous preconditioning increases invasion and metastatic dissemination in colorectal cancer models

Mouse colorectal cancer (CRC) models generated by orthotopic microinjection of human CRC cell lines reproduce the pattern of lymphatic, haematological and transcoelomic spread but generate low metastatic efficiency. Our aim was to develop a new strategy that could increase the metastatic efficiency of these models. We used subcutaneous implantation of the human CRC cell lines HCT116 or SW48 prior to their orthotopic microinjection in the cecum of nude mice (SC+ORT). This subcutaneous preconditioning significantly enhanced metastatic dissemination. In the HCT116 model it increased the number and size of metastatic foci in lymph nodes, lung, liver and peritoneum, whereas, in the SW48 model, it induced a shift from non-metastatic to metastatic. In both models the number of apoptotic bodies in the primary tumour in the SC+ORT group was significantly reduced compared with that in the direct orthotopic injection (ORT) group. Moreover, in HCT116 tumours the number of keratin-positive tumour buddings and single epithelial cells increased at the invasion front in SC+ORT mice. In the SW48 tumour model, we observed a trend towards a higher number of tumour buds and single cells in the SC+ORT group but this did not reach statistical significance. At a molecular level, the enhanced metastatic efficiency observed in the HCT116 SC+ORT model was associated with an increase in AKT activation, VEGF-A overexpression and downregulation of β1 integrin in primary tumour tissue, whereas, in SW48 SC+ORT mice, the level of expression of these proteins remained unchanged. In summary, subcutaneous preconditioning increased the metastatic dissemination of both orthotopic CRC models by increasing tumour cell survival and invasion at the tumour invasion front. This approach could be useful to simultaneously study the mechanisms of metastases and to evaluate anti-metastatic drugs against CRC.

Clinical significance of tumor budding detection in stage II colon cancer

To investigate the association of tumor budding with recurrence and survival of patients with stage II colon cancer, in order to identify patients with high-risk recurrence who may benefit from adjuvant therapy. Clinical data of 112 stage II colon cancer patients in Guangzhou Red Cross Hospital between 1998 and 2007 were analyzed retrospectively. The degree of tumor budding was assessed by two observers and classified according to the number of tumor buds in the area with the greatest budding intensity on HE stain slides, as high-grade budding (≥10, n=30) and low-grade budding (≤9, n=82). Progression-free and cancer-specific survival were analyzed using the Kaplan-Meier method and Cox regression. All the patients were followed up and the median follow-up was 78 months. The 5-year progression-free survival rates for patients with high-grade and low-grade budding were 65.3% and 90.7% respectively (P=0.008). The 5-year cancer-specific survival rates were 72.1% and 93.8% respectively (P=0.001). Cox regression analysis demonstrated tumor budding was an independent predictor of disease progression (RR=4.572, 95%CI:2.218-11.746, P=0.002) and cancer-related death (RR=4.116, 95%CI:1.657-10.384, P=0.012). Tumor budding is a strong prognostic index for adverse outcome in stage II colon cancer patients,which may serve as a prognostic marker to identify patients with high risk of recurrence who may benefit from adjuvant therapy.

Clinical significance of tumor budding in colorectal cancer.

422 Background: Tumor budding was defined as an isolated single cancer cell or a small cluster of cancer cells at the invasive margins. We assessed the clinical significance of tumor budding, as a predictor of outcomes in patients with non-metastatic colorectal cancer. Methods: We studied a total of 148 patients with colorectal cancer who underwent curative resection. Tumor budding was assessed on slides stained with hematoxylin and eosin (H&amp;E). Tissue specimens including the entire invasive margin from largest cut sections of the whole tumor were examined. Tumor budding was not classified according to previously described classification. The actual number of tumor budding along the entire invasive margin was counted at a magnification of x200 with the use of light microscopy. We determined cut-off point of tumor budding, lymph node ratio and carcinoembryonic antigen (CEA) with receiver operating characteristic (ROC) curve. Results: Univariate analysis revealed that poorly differentiation (p=0.009), lymphatic invasion (p=0.035) venous invasion (p=0.007), CEA &gt;6.3 (p=0.0007) and tumor budding &gt;13 (p=0.0006) were significantly related to poor survival. Cumulative five survival rates differed significantly between patients with tumor budding ≤13 (92.3%) and those with tumor budding &gt;13 (73.1 %). Multivariate analysis with Cox’s regression analysis demonstrated that tumor budding &gt;13 (hazard ratio=4.925, p=0.003), poorly differentiation (hazard ratio=3.696, p=0.01) and CEA &gt;6.3 (hazard ratio=3.085, p=0.024) were independent prognostic factors for overall survival. CEA &gt;6.3 (hazard ratio=2.361, p=0.034) and tumor budding &gt;20 (hazard ratio=3.293, p=0.008) were significant prognostic predictors for disease free survival Conclusions: Tumor budding is useful for prognosis and identifying patients with colorectal cancer who have a high-risk of disease recurrence after curative surgery. The proper cut-off level of tumor budding is 13.

Immune response to tumor budding ratio: A new potential prognostic score to improve risk stratification for patients with colorectal cancer.

e14033 Background: Tumor budding in colorectal cancer is the histologic hallmark of epithelial mesencyhmal transition and is considered an additional prognostic factor by the International Union against Cancer. Abundant tumor budding is associated with lymph node metastasis, vascular invasion and distant metastasis and inversely related to peritumoral lymphocytic inflammation implicating tumor immunity in events occurring at the invasive front. Recently a high CD8+/budding ratio was identified as an independent prognostic factor. The aim of this study was to assess the ratio of various immune cell types to tumor budding ratio in order to define a potential new prognostic score for patients with this disease. Methods: Whole tissue sections from 297 patients with colorectal cancer were cut in series and double immunostaining was performed for CK22 with antibodies directed against CD3, CD8, CD16, CD20, CD21, CD56, CD68, CD138, Foxp3, Granzyme B, and mast cell tryptase. The densest region of tumor budding at the invasive front was identified. Using a 40x objective, the number of tumor buds and positively stained cells for each marker were counted. Results: All protein markers where inversely correlated with the number of tumor buds. After multivariable analysis with pT category, pN category and vascular invasion, a hierarchy of marker/budding ratios identified high Granzyme B+/budding (HR: 0.5 [0.31-0.82; p = 0.006]) as having the strongest positive independent effect on outcome, followed by high CD68+/budding (HR: 0.52 [0.33- 0.84; p = 0.007]), CD8+/budding (HR: 0.54 [0.34-0.84; p = 0.007]), CD16+/budding (HR: 0.56 [0.35-0.9; p = 0.015]), FoxP3+/budding (HR: 0.57 [0.35-0.91; p = 0.019]) and CD3+/budding (HR: 0.58 [0.37-0.9; p = 0.017]). Conclusions: High ratios of CD8+ cytotoxic T- lymphocytes, granzyme B+ or CD68+ cells to tumor budding represent not only a possible mechanism by which budding cells are prevented from disseminating into vessels, but also may lead to an additional prognostic score to improve risk stratification for patients with colorectal cancer. No significant financial relationships to disclose.

Expression of E-cadherin and β-catenin is Altered at Tumor Budding Sites, Whose Number is Associated with the Progression of Colorectal Carcinoma

Background : Tumor budding is present in the stroma at the invasive margin of colorectal carcinomas (CRC). The disintegration of cell adhesion molecules is closely related to this process. This study investigated the role of tumor budding in the progression of CRC, and compared the expression of b-catenin and E-cadherin between tumor budding and tumor center to determine whether epithelial-to-mesenchymal transitions (EMTs) occur in tumor budding. Methods : The number of tumor budding (NTB) instances was determined in 58 cases of CRC, and immunoreactivities of E-cadherin and b-catenin were compared at the tumor center and at the tumor budding site. Immunohistochemical staining for vimentin was also done. Results : Tumor budding was seen in 52 tumors (90%). There were significant associations between NTB and cliniopathologic parameters such as tumor depth, nodal metastasis and clinical stage. Expression of cytoplasmic and nuclear b-catenin were significantly higher at tumor budding sites than in the tumor center. In contrast, expression of membranous and cytoplasmic E-cadherin were significantly higher in the tumor center than at the tumor budding sites. Vimentin was expressed at tumor budding foci of only 2 cases (3%). Conclusions : This study suggests that EMT occurs at tumor budding, and that NTB may be a good marker for predicting a poor prognosis in CRC.

Tumor budding and evidence-based treatment of T2 rectal carcinomas

The validity of the histological criteria in deciding additional bowel resection after local excision of T2 rectal carcinomas is questioned. In 72 T2 colorectal carcinomas resected by major surgery, the associations between lymph node metastasis (LNM) and clinicopathologic parameters were examined statistically, a prediction formula for LNM was constructed and decision analysis was attempted. Multivariate analysis showed that female gender and a greater number of tumor budding were significantly associated with LNM. The probability of LNM can be calculated as follows; Z = 0.037 x (budding number) + 2.08 x (SEX; male, 1; female, 2) - 5.736; Probability = 1/1 + e(-Z). When a 75-year-old patient has pulmonary complications, the operative risk is assumed to be over 2%. If a number of tumor budding is 0, the risk of LNM is calculated as 2.4% in a male and 17.1% in a female patient. On the assumption that the risk of liver metastasis is half of that of LNM, and the salvageabilities after LNM and liver metastasis are 20% and 50%, respectively, observation policy is justified for a male patient, whereas additional surgery should be undertaken for a female patient. A number of tumor budding may be useful for determining the individualized treatment of T2 rectal carcinomas.

Coexpression of matrilysin and laminin-5 gamma2 chain may contribute to tumor cell migration in colorectal carcinomas.

We attempted to examine the correlation between matrilysin and laminin-5 gamma2 chain expression with reference to the number of dedifferentiation units along the entire invasive front (tumor budding). Immunostaining for hMMP-7 and laminin-5 gamma2 chain was performed in 50 T1 colorectal carcinomas, and immunoreactivity was evaluated at the invasive front of the tumor. On hematoxylin-eosin sections, the number of tumor budding was counted. The localization of matrilysin tended to be widespread compared with that of laminin-5 gamma2 chain. Matrilysin and laminin-5 gamma2 chain expression were positive in 28 (56%) and 15 (30%) tumors respectively. There was a significant correlation between matrilysin and laminin-5 gamma2 chain expression (P = 0.02). Matrilysin(+)/laminin-5 gamma2 chain(+) tumors had a significantly greater amount of tumor budding than matrilysin(-)/laminin-5 gamma2 chain(-) tumors (P = 0.003) or matrilysin(+)/laminin-5 gamma2 chain(-) tumors (P = 0.03). In conclusions, coexpression of matrilysin and laminin-5 gamma2 chain may contribute to tumor cell migration in colorectal carcinomas.