Relationship Between Tumor Budding And The Prognosis And Biological Behavior Of Colorectal Cancer

INTRODUCTIONThe colorectal cancer is one of malignant tumor, which have high incidence rateand poor prognosis. The recurrence and metastasis of tumor are the major factor whichdecide the result of treatment and the prognosis. In order to elevate the early diagnosisrate and the result of treatment, the surgery and pathology scholar dedicate to find afactor that represent the aggressive biological behavior of coloretal cancer and thereasonable staging method of tumor. The precisely molecule mechanism of tumormetastasis still not known now. The metastasis is considered as a multigene participant,multi-step complex process, including tumour cells migrating out of the main tumour,adhesion, degradation, motility, angiogenesis and lymphogenesis and escaping fromimmune surveillance. The dissociation of the organized tumor cell complexes intoisolated cancer cells and loss of most of the cytologic features of differentiation is acrucial event in the tumor invasion and metastatic process. Tumor budding just the firststep. The oncologic significance of tumor budding along the invasive margin was firstdescribed by Imai in 1949. Several Investigators have highlighted the histologicalphenomenon which represents these events, using the term tumour 'budding', andreported this histological feature and its relation to both metastasis and long-termsurvival. The definition of budding was proposed by Morodomi, wherein is buddingdefined as an isolated single cancer cell or a cluster composed of fewer than five undifferentiated cancer cells appearing to bud from a large cancer gland at the invasivefront. The relationship between the intensity of tumor budding and the prognosis andbiological behavior was retrospectively studied in this investigation from 94 patientswith colorectal cancer who underwent radical excision at Department of Oncologic,surgery, Affiliated First Hospital, China Medical University, the aim is to providebasis for earlier period right diagnosis and draw up reasonable of the treatment project.MATERIALS AND METHODSThe colorectal cancer (The patients comprised 50 men and 44 women, withaverage age at operation of 57.5 years) from 94 patients who underwent potentiallycurative resection between January 2000 and December 2001 at Department ofOncologic, surgery, Affiliated First Hospital, China Medical University, were selectedfor this study. Sections representing the invasive tumor margin from specimens fixed informalin and embedded in paraffin were stained with hematoxylin and eosin formicroscopic examinations to find the presence or not and the intensity of tumorbudding. The presence of budding was determined according to criteria proposed byUeno et al, wherein budding is defined as an isolated single cancer cell or a clustercomposed of fewer than five undifferentiated cancer cells appearing to bud from a largecancer gland at the invasive front. For tumor budding quantification, every slide wasscanned at lower power magnification(×10 objective lens) to identify areas of thehighest density of tumor budding. In each tumor, three areas considered to have thehighest density were selected and the number of budding in each of these areas wascounted using the 20-power objective lens. Tumor budding was expressed as theintensity of tumor budding, which was defined as the highest number of tumor buddingamong these three areas. Dividing patients into two groups by the intensity oftumour" budding'(＜10;＞=10).RESULTThe intensity of tumor budding was correlated with the lymph node metastasis(P＜0.001),as well as the depth of cancer invasion (P=0.004)and the differentiation of tumor(P=0.03). There was a highly significant difference in 5-year survival rates indifferent groups between high-grade 'budding'and low-grade 'budding' (P＜0.001)Postoperative survival for patients with budding-positive stageâ…¡lesions did not differsignificantly from that for patients with stageâ…¢lesions (P=0.116). The 5-year survivalrates of the moderately differentiated high-grade 'budding', poorly differentiated were27% and 62% respectively; there was a highly significant difference in survival curvebetween the two groups(P=0.040); the prognosis of the former is more worse. Patientswith high-grade 'budding' had a significantly higher incidence of liver metastasis, lungmetastasis and bone metastasis than those with low-grade 'budding' (P＜0.001).Multivariate Cox model analysis showed the intensity of tumor budding was the mostsignificant independent prognostic factor.CONCLUSIONThe results in this study shows that the intensity of tumor budding wassignificantly correlated with the lymph node metastasis (P＜0.001),as well as the depthof cancer invasion (P=0.004)and the differentiation of tumor(P=0.03).The prognosis ofthe high-grade 'budding' is more worse than that of the low-grade 'budding' in thesame TNM classification (P＜0.001); Postoperative survival for patients withbudding-positive stageâ…¡lesions did not differ significantly from that for patients withstageâ…¢lesions (P=0.116); It suggestion that the intensity of tumor budding is a goodindex to estimate prognosis of coloretal cancer. The prognosis of the high-grade'budding' is more worse in the same T staging; The 5-year survival rates of thehigh-grade 'budding' of T₃ staging, T₄ staging were 26% and 30% respectively; therewas not significant difference in prognosis between the two groups (P=0.959). Theprognosis of the high-grade 'budding' is more worse than that of the low-grade'budding' in the same macroscopic tpye (P＜0.001); The prognosis of the high-grade'budding' is more worse than that of the low-grade 'budding' in the same grown pattern (P＜0.001); they suggestion that the intensity of tumor budding is a good indexwhich is independent from T staging, macroscopic tpye, grown pattern, to estimate prognosis and the aggressive biological behavior of coloretal cancer. Postoperativerecurrence rate was significantly higher in patients with high-grade 'budding' than inpatients with low-grade 'budding', there was a highly significant difference betweenthe two groups(P＜0.001), it suggestion that the intensity of tumor budding is a goodindex to predict the recurrence and metastasis of coloretal cancer.