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Thrombomodulin expression in colorectal carcinoma is protective and correlates with survival.

Hanly AM, Redmond M, Winter DC, Brophy S, Deasy JM, Bouchier-Hayes DJ, Kay EW - Br. J. Cancer (2006)

Bottom Line: TM expression decreases as overall stage and tumour size increase (P=0.03).Survival rate was poorer in those patients who were TM negative compared with those who were positive (P<0.01).This study demonstrates that loss of TM is a key indicator in tumour biology and prognosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.

ABSTRACT
Thrombomodulin (TM) is an endothelial receptor that exhibits anticoagulant, antifibrinolytic and anti-inflammatory activity by inhibiting thrombin and cellular adhesion. In this study, the expression and significance of TM was examined in primary colorectal cancer and its prognostic implications explored. TM immunostaining was performed on formalin-fixed, paraffin-embedded tissue sections, from primary lesions of 200 patients with colorectal carcinoma. Institutional Ethical approval was granted and clinical data retrieved from patients' records. All normal colonic tissue expressed TM on endothelial cells. TM tumour cell expression was demonstrated in 53 (26.5%) cases and 147 (73.5%) showed no neoplastic cell staining. On univariate and multivariate analysis TM expression on tumour cells correlated significantly with tumour stage, differentiation, Jass score and 5 year survival. TM expression decreases as overall stage and tumour size increase (P=0.03). In all, 91% TM positive tumours were well differentiated and 85% of TM negative tumours were poorly differentiated (P<0.01). Five year survival rates of patients with positive and negative TM expression were 71 and 41%, respectively. Survival rate was poorer in those patients who were TM negative compared with those who were positive (P<0.01). A total of 101 (50.5%) of the cases were node negative. In this group, 5 year survival rates of patients with positive and negative TM expression were 87.5 and 37.8%, respectively, demonstrating a poorer survival rate for those who are node negative and TM negative at the time of surgery (P<0.001). This study demonstrates that loss of TM is a key indicator in tumour biology and prognosis.

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Isotype-matched primary monoclonal antibody negative control.
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fig3: Isotype-matched primary monoclonal antibody negative control.

Mentions: Specimens from 200 consecutive patients who underwent surgery for primary adenocarcinoma of the colon between 1994 and 1999 were included in this study. The median (range) age of patients was 69 (34–90) years (male 66.5%, female 33.5%). Patients with radiological evidence of metastasis, or who had preoperative chemo or radiotherapy, were excluded. Ethics approval was granted and relevant information was collected from clinical records, primary care physicians and, where necessary, patient contact. Location of tumours, overall stage and tumour stage classified by the TNM classification are outlined in Tables 1, 2 and 3, respectively. Evaluation of malignancy was based on original haematoxylin and eosin stained sections at the time of diagnosis. TM expression in the primary tumours was examined immunohistochemically. Formalin-fixed paraffin-embedded colorectal tumours were retrieved from the archives. Sections were cut at 4 μm, deparaffinised and rehydrated in descending grades of alcohol (100–70%). Following heat-mediated antigen retrieval, slides were run on an automated immuno-stainer (Nexes from Ventana, AZ, USA). Primary antibody was a mouse monoclonal antibody raised against the EGF domains 4–6 of TM (Dako Glostrup, Denmark; 1 : 50 dilution). The immunostaining was developed using diaminobenzidine as a chromagen. Vascular endothelium acted as a positive internal control (Figures 1 and 2), the primary antibody was omitted for negative controls and this was confirmed using an isotype-matched primary monoclonal antibody (DAKO Cytomation M0792 at 1 : 2000 dilution) (Figure 3). Results were quantitatively evaluated by two blinded pathologists. Slides were graded according to intensity of staining on tumour cells and were classified as 0, completely negative; +1, under 10% of neoplastic cells stained; +2 10–50% of neoplastic cells stained and +3 over 50% of neoplastic cells stained. No slides demonstrated +3 staining and no statistical difference was noted between +1 and +2 staining when compared with tumour grade, stage and overall survival. Therefore, analysis was performed using two groups, TM positive and TM negative.


Thrombomodulin expression in colorectal carcinoma is protective and correlates with survival.

Hanly AM, Redmond M, Winter DC, Brophy S, Deasy JM, Bouchier-Hayes DJ, Kay EW - Br. J. Cancer (2006)

Isotype-matched primary monoclonal antibody negative control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361416&req=5

fig3: Isotype-matched primary monoclonal antibody negative control.
Mentions: Specimens from 200 consecutive patients who underwent surgery for primary adenocarcinoma of the colon between 1994 and 1999 were included in this study. The median (range) age of patients was 69 (34–90) years (male 66.5%, female 33.5%). Patients with radiological evidence of metastasis, or who had preoperative chemo or radiotherapy, were excluded. Ethics approval was granted and relevant information was collected from clinical records, primary care physicians and, where necessary, patient contact. Location of tumours, overall stage and tumour stage classified by the TNM classification are outlined in Tables 1, 2 and 3, respectively. Evaluation of malignancy was based on original haematoxylin and eosin stained sections at the time of diagnosis. TM expression in the primary tumours was examined immunohistochemically. Formalin-fixed paraffin-embedded colorectal tumours were retrieved from the archives. Sections were cut at 4 μm, deparaffinised and rehydrated in descending grades of alcohol (100–70%). Following heat-mediated antigen retrieval, slides were run on an automated immuno-stainer (Nexes from Ventana, AZ, USA). Primary antibody was a mouse monoclonal antibody raised against the EGF domains 4–6 of TM (Dako Glostrup, Denmark; 1 : 50 dilution). The immunostaining was developed using diaminobenzidine as a chromagen. Vascular endothelium acted as a positive internal control (Figures 1 and 2), the primary antibody was omitted for negative controls and this was confirmed using an isotype-matched primary monoclonal antibody (DAKO Cytomation M0792 at 1 : 2000 dilution) (Figure 3). Results were quantitatively evaluated by two blinded pathologists. Slides were graded according to intensity of staining on tumour cells and were classified as 0, completely negative; +1, under 10% of neoplastic cells stained; +2 10–50% of neoplastic cells stained and +3 over 50% of neoplastic cells stained. No slides demonstrated +3 staining and no statistical difference was noted between +1 and +2 staining when compared with tumour grade, stage and overall survival. Therefore, analysis was performed using two groups, TM positive and TM negative.

Bottom Line: TM expression decreases as overall stage and tumour size increase (P=0.03).Survival rate was poorer in those patients who were TM negative compared with those who were positive (P<0.01).This study demonstrates that loss of TM is a key indicator in tumour biology and prognosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.

ABSTRACT
Thrombomodulin (TM) is an endothelial receptor that exhibits anticoagulant, antifibrinolytic and anti-inflammatory activity by inhibiting thrombin and cellular adhesion. In this study, the expression and significance of TM was examined in primary colorectal cancer and its prognostic implications explored. TM immunostaining was performed on formalin-fixed, paraffin-embedded tissue sections, from primary lesions of 200 patients with colorectal carcinoma. Institutional Ethical approval was granted and clinical data retrieved from patients' records. All normal colonic tissue expressed TM on endothelial cells. TM tumour cell expression was demonstrated in 53 (26.5%) cases and 147 (73.5%) showed no neoplastic cell staining. On univariate and multivariate analysis TM expression on tumour cells correlated significantly with tumour stage, differentiation, Jass score and 5 year survival. TM expression decreases as overall stage and tumour size increase (P=0.03). In all, 91% TM positive tumours were well differentiated and 85% of TM negative tumours were poorly differentiated (P<0.01). Five year survival rates of patients with positive and negative TM expression were 71 and 41%, respectively. Survival rate was poorer in those patients who were TM negative compared with those who were positive (P<0.01). A total of 101 (50.5%) of the cases were node negative. In this group, 5 year survival rates of patients with positive and negative TM expression were 87.5 and 37.8%, respectively, demonstrating a poorer survival rate for those who are node negative and TM negative at the time of surgery (P<0.001). This study demonstrates that loss of TM is a key indicator in tumour biology and prognosis.

Show MeSH
Related in: MedlinePlus