AIM: To clarify the usefulness of immunohistochemical molecular markers in predicting lymph node metastasis of submucosal colorectal cancer. METHODS: We examined microvessel density, lymphatic vessel density, the Ki-6...AIM: To clarify the usefulness of immunohistochemical molecular markers in predicting lymph node metastasis of submucosal colorectal cancer. METHODS: We examined microvessel density, lymphatic vessel density, the Ki-67 labeling index, expression of MUC1 and Matrix metalloproteinase-7 (MMP-7) in tumor cells, and expression of cathepsin D in stromal cells at the invasive front by immunostaining of samples resected from 214 patients with submucosal colorectal cancer. Pathologic features were assessed on hematoxylin-eosin- stained samples. We evaluated the relations between clinicopathologic/immunohistochemical features and lymph node metastasis. RESULTS: Lesions of the superficial type, with an unfavorable histologic grade, budding, lymphatic involvement, high microvessel density (≥ 40), high lymphatic vessel density (≥ 9), high Ki-67 labeling index (≥ 42), and positivity of MUC1, cathepsin D, and MMP-7 showed a significantly high incidence of lymph node metastasis. Multivariate analysis revealed that high microvessel density, unfavorable histologic grade, cathepsin D positivity, high lymphatic vessel density, superficial type, budding, and MUC1 positivity were independent risk factors for lymph node metastasis.A combined examination with four independent immunohistochemical markers (microvessel density, cathepsin D, lymphatic vessel density, and MUC1) revealed that all lesions that were negative for all markers or positive for only one marker were negative for lymph node metastasis. CONCLUSION: Analysis of a combination of immuno- histochemical molecular markers in endoscopically resected specimens of submucosal colorectal cancer allows prediction of curability regardless of the pathologic features visible of hematoxylin-eosin-stained sections.展开更多
AIM： To investigate the distribution pattern of lymphatic vessels and microvessels in sporadic colorectal carcinoma （SCRC） and their relationship to metastasis and prognosis. METHODS： The lymphatic vessel density ...AIM： To investigate the distribution pattern of lymphatic vessels and microvessels in sporadic colorectal carcinoma （SCRC） and their relationship to metastasis and prognosis. METHODS： The lymphatic vessel density （LVD） and microvessel density （MVD） in tumor tissue obtained from 132 patients with primary SCRC, including 74 with metastases and 58 without metastases, were evaluated by immunohistochemistry using antibodies directed against D2-40 and yon Willebrand factor （vWF）. RESULTS： （1） The lymphatic vessels and microvessels at central portions of SCRC often had a reticular architecture with numerous tiny and ill-defined lumina, while those at tumor borders had large and open lumina. The LVD and MVD were both obviously higher in colorectal cancer patients with metastases than in those without （P 〈 0.001）. （2） For each one lymphatic vessel increased, there was a 1.45-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of LVD in predicting metastasis or non-metastasis in SCRC were 71.62% and 56.90%, respectively, and the corresponding LVD was 5. For each one microvessel increased, there was a 1.11-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of MVD were 66.22% and 51.72%, respectively. （3） Double labeling immunohistochemistry showed D2-40 immunoreactivity to be specific for lymphatic vessels. （4） Univariate analysis indicated that high LVD, high MVD, as well as co-accounting of high LVD and high MVD were associated with patient＇s poor disease-free survival （Puni 〈 0.05）; multivariate analysis indicated that co-accounting of LVD and MVD was an independent prognostic factor of colorectal cancer, CONCLUSION： D2-40 is a new specific antibody for lymphatic endothelial cells. Lymphogenesis and angiogenesis are commonly seen in SCRC, especially at tumor borders. The detection of LVD and MVD at tumor borders may be useful in predicting metastasis and prognosis in patients with SCRC, and, in particular, coaccounting of LVD and MVD might be a useful prognostic factor in SCRC.展开更多
AIM： TO investigate colonic endocrine cells in lympho- cytic colitis （LC） patients. METHODS： Fifty-seven patients with LC were in- cluded. These patients were 41 females and 16 males, with an average age of 49 yea...AIM： TO investigate colonic endocrine cells in lympho- cytic colitis （LC） patients. METHODS： Fifty-seven patients with LC were in- cluded. These patients were 41 females and 16 males, with an average age of 49 years （range 19-84 years）. Twenty-seven subjects that underwent colonoscopy with biopsies were used as controls. These subjects underwent colonoscopy because of gastrointestinal bleeding or health worries, where the source of bleed- ing was identified as haemorrhoids or angiodysplasia. They were 19 females and 8 males with an average age of 49 years （range 18-67 years）. Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. Biopsies were fixed in 4% buffered paraformaldehyde, embedded in paraffin and cut into 5 μm-thick sections. The sections immunostained by the avidin-biotin-complex method for se- rotonin, peptide YY （PYY）, pancreatic polypeptide （PP） enteroglucagon and somatostatin cells. The cell densi- ties were quantified by computerised image analysis using Olympus software. RESULTS： The colon of both the patient and the control subjects were macroscopically normal. Histo- pathological examination of colon biopsies from con- trols revealed normal histology. All patients fulfilled the diagnosis criteria required for of LC： an increase in intraepithelial lymphocytes （〉 20 lymphocytes/100 epithelial cells） and surface epithelial damage with increased lamina propria plasma cells and absent or minimal crypt architectural distribution. In the colon of both patients and control subjects, serotonin-, PYY-, PP-, enteroglucagon- and somatostatin-immunoreac- tive cells were primarily located in the upper part of the crypts of Lieberk0hn. These cells were basket- or flask-shaped. There was no statistically significant dif- ference between the right and left colon in controls with regards to the densities of serotonin- and PYY- immunoreactive cells （P = 0.9 and 0.1, respectively）. Serotonin cell density in the right colon in controls was 28.9 ± 1.8 and in LC patients 41.6±2.6 （P = 0.008）. In the left colon, the corresponding figures were 28.5± 1.9 and 42.4± 2.9, respectively （P = 0.009）. PYY cell density in the right colon of the controls was 10.1 ± 1 and of LC patients 41 ± 4 （P = 0.00006）. In the left colon, PYY cell density in controls was 6.6± 1.2 and in LC patients 53.3 ± 4.6 （P = 0.00007）. CONCLUSION： The change in serotonin cells could be caused by an interaction between immune cells and serotonin cells, and that of PYY density might be sec- ondary.展开更多
基金a Grant from the Japanese Society of Gastro-enterological Endoscopy, Chugoku Branch
文摘AIM: To clarify the usefulness of immunohistochemical molecular markers in predicting lymph node metastasis of submucosal colorectal cancer. METHODS: We examined microvessel density, lymphatic vessel density, the Ki-67 labeling index, expression of MUC1 and Matrix metalloproteinase-7 (MMP-7) in tumor cells, and expression of cathepsin D in stromal cells at the invasive front by immunostaining of samples resected from 214 patients with submucosal colorectal cancer. Pathologic features were assessed on hematoxylin-eosin- stained samples. We evaluated the relations between clinicopathologic/immunohistochemical features and lymph node metastasis. RESULTS: Lesions of the superficial type, with an unfavorable histologic grade, budding, lymphatic involvement, high microvessel density (≥ 40), high lymphatic vessel density (≥ 9), high Ki-67 labeling index (≥ 42), and positivity of MUC1, cathepsin D, and MMP-7 showed a significantly high incidence of lymph node metastasis. Multivariate analysis revealed that high microvessel density, unfavorable histologic grade, cathepsin D positivity, high lymphatic vessel density, superficial type, budding, and MUC1 positivity were independent risk factors for lymph node metastasis.A combined examination with four independent immunohistochemical markers (microvessel density, cathepsin D, lymphatic vessel density, and MUC1) revealed that all lesions that were negative for all markers or positive for only one marker were negative for lymph node metastasis. CONCLUSION: Analysis of a combination of immuno- histochemical molecular markers in endoscopically resected specimens of submucosal colorectal cancer allows prediction of curability regardless of the pathologic features visible of hematoxylin-eosin-stained sections.
基金Supported by the a grant from the Sciences and Techni-que Development Foundation of Shanghai, No. 064119512, 024119010
文摘AIM： To investigate the distribution pattern of lymphatic vessels and microvessels in sporadic colorectal carcinoma （SCRC） and their relationship to metastasis and prognosis. METHODS： The lymphatic vessel density （LVD） and microvessel density （MVD） in tumor tissue obtained from 132 patients with primary SCRC, including 74 with metastases and 58 without metastases, were evaluated by immunohistochemistry using antibodies directed against D2-40 and yon Willebrand factor （vWF）. RESULTS： （1） The lymphatic vessels and microvessels at central portions of SCRC often had a reticular architecture with numerous tiny and ill-defined lumina, while those at tumor borders had large and open lumina. The LVD and MVD were both obviously higher in colorectal cancer patients with metastases than in those without （P 〈 0.001）. （2） For each one lymphatic vessel increased, there was a 1.45-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of LVD in predicting metastasis or non-metastasis in SCRC were 71.62% and 56.90%, respectively, and the corresponding LVD was 5. For each one microvessel increased, there was a 1.11-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of MVD were 66.22% and 51.72%, respectively. （3） Double labeling immunohistochemistry showed D2-40 immunoreactivity to be specific for lymphatic vessels. （4） Univariate analysis indicated that high LVD, high MVD, as well as co-accounting of high LVD and high MVD were associated with patient＇s poor disease-free survival （Puni 〈 0.05）; multivariate analysis indicated that co-accounting of LVD and MVD was an independent prognostic factor of colorectal cancer, CONCLUSION： D2-40 is a new specific antibody for lymphatic endothelial cells. Lymphogenesis and angiogenesis are commonly seen in SCRC, especially at tumor borders. The detection of LVD and MVD at tumor borders may be useful in predicting metastasis and prognosis in patients with SCRC, and, in particular, coaccounting of LVD and MVD might be a useful prognostic factor in SCRC.
文摘AIM： TO investigate colonic endocrine cells in lympho- cytic colitis （LC） patients. METHODS： Fifty-seven patients with LC were in- cluded. These patients were 41 females and 16 males, with an average age of 49 years （range 19-84 years）. Twenty-seven subjects that underwent colonoscopy with biopsies were used as controls. These subjects underwent colonoscopy because of gastrointestinal bleeding or health worries, where the source of bleed- ing was identified as haemorrhoids or angiodysplasia. They were 19 females and 8 males with an average age of 49 years （range 18-67 years）. Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. Biopsies were fixed in 4% buffered paraformaldehyde, embedded in paraffin and cut into 5 μm-thick sections. The sections immunostained by the avidin-biotin-complex method for se- rotonin, peptide YY （PYY）, pancreatic polypeptide （PP） enteroglucagon and somatostatin cells. The cell densi- ties were quantified by computerised image analysis using Olympus software. RESULTS： The colon of both the patient and the control subjects were macroscopically normal. Histo- pathological examination of colon biopsies from con- trols revealed normal histology. All patients fulfilled the diagnosis criteria required for of LC： an increase in intraepithelial lymphocytes （〉 20 lymphocytes/100 epithelial cells） and surface epithelial damage with increased lamina propria plasma cells and absent or minimal crypt architectural distribution. In the colon of both patients and control subjects, serotonin-, PYY-, PP-, enteroglucagon- and somatostatin-immunoreac- tive cells were primarily located in the upper part of the crypts of Lieberk0hn. These cells were basket- or flask-shaped. There was no statistically significant dif- ference between the right and left colon in controls with regards to the densities of serotonin- and PYY- immunoreactive cells （P = 0.9 and 0.1, respectively）. Serotonin cell density in the right colon in controls was 28.9 ± 1.8 and in LC patients 41.6±2.6 （P = 0.008）. In the left colon, the corresponding figures were 28.5± 1.9 and 42.4± 2.9, respectively （P = 0.009）. PYY cell density in the right colon of the controls was 10.1 ± 1 and of LC patients 41 ± 4 （P = 0.00006）. In the left colon, PYY cell density in controls was 6.6± 1.2 and in LC patients 53.3 ± 4.6 （P = 0.00007）. CONCLUSION： The change in serotonin cells could be caused by an interaction between immune cells and serotonin cells, and that of PYY density might be sec- ondary.
