p53 overexpression in flat serrated adenomas and flat tubular adenomas of the colorectal mucosa

The expression of the p53 protein was investigated in flat serrated neoplasias as well as in other histological phenotypes of flat or exophytic hyperplasias or neoplasias of the colorectal, mucosa. A total of 104 such lesions were analyzed: 24 were flat serrated neoplasias (22 flat serrated adenomas and 2 flat serrated adenocarcinomas), 26 flat tubular adenomas, 17 flat hyperplastic polyps, 29 exophytic tubular and/or villous neoplasias (23 adenomas and 6 exophytic adenocarcinomas) and the remaining 8, exophytic hyperplastic polyps. Deparaffinized, rehydrated sections were treated immunohistochemically to detect those overexpressing the p53 protein. Lesions having slight (+), moderate (++) or intense (+++) staining were considered immunoreactive. The results showed that 50% of the flat serrated adenomas with low-grade dysplasia (LGD) and 66.7% of those with high-grade dysplasia (HGD) had p53 immunoreactivity. None of the flat tubular or of the exophytic adenomas with LGD expressed p53, but immunoreactivity was present in 61.5% of the flat tubular adenomas with HGD and in 52.3% of the exophytic adenomas with HGD. All adenocarcinomas had an intense p53 reaction. Weak p53 expression was demonstrated by 11.7% of the flat hyperplastic polyps but none of the exophytic polyps reacted. The occurrence of p53 expression in flat serrated adenomas with LGD suggested that, despite its low histological profile, one-half of those lesions could be biologically already committed to independent growth. The occurrence of p53 expression in nearly 12% of the flat hyperplastic polyps was totally unexpected and deserves further investigation. Flat serrated adenoma emerges as a novel, independent histological entity among the various phenotypes of flat neoplasias of the colorectal mucosa.     

Expression of mutant p53 protein and CD44 variant proteins in colorectal tumorigenesis.

Colorectal tumorigenesis evolves through a series of molecular genetic changes, providing putative markers for tumour progression. This study investigated the relation between expression of the tumour suppressor gene p53 and splice variants v5 and v6 of the cell adhesion molecule CD44 by immunohistochemistry on tissue samples of early adenomas (n = 12), late adneomas (n = 12), Dukes's A and B carcinomas (n = 21), and Dukes's C and D carcinomas (n = 22) and compared these results with expression of these proteins in normal colonic mucosa (n = 17). A statistically significant trend of increasing expression was seen for both p53 (p < 0.005) and CD44 variant exon v6 (p < 0.0005) in subsequent stages of this tumour progression model. High expression of CD44 v5 was seen in most colorectal neoplasms (83%-96%), independent of stage. A statistically significant correlation was present between p53 expression and expression of variant v6 of CD44 (p < 0.01). Both p53 expression and CD44 v6 expression in adenomas increased with the degree of dysplasia (p < 0.05). The results of this study show that mutant p53 protein and variant v6 of the CD44 glycoprotein are markers of tumour progression in colorectal cancer.     

The expression of CD66a and possible roles in colorectal adenoma and adenocarcinoma

Background The aim of our study was to analyze the expression and possible role of CD66a in colorectal adenoma and adenocarcinoma and the relationship between its expression and pre-operation serum carcinoembryonic antigen (CEA) level and tumor stage in patients with colorectal adenocarcinomas. Methods Paraffin-embedded sections from 184 patients including 42 colorectal adenomas with low-grade dysplasia, 43 adenomas with high-grade dysplasia, and 99 adenocarcinomas were collected for this study. Immunohistochemical analysis was performed, and the expression and the location of CD66a were evaluated and were correlated with β-catenin nuclear expression. Results The expression of CD66a was found not only in the apical membrane of neoplastic glands but also in secretion within the lumen of the neoplastic glands including adenomas and adenocarcinomas. Expressions of secreted CD66a were of higher level in adenocarcinoma than in adenoma with high-grade dysplasia and adenoma with low-grade dysplasia (p < 0.0001). High expression of secreted CD66a was also associated with tumor stage, invasion, and pre-operation serum CEA level of patients with colorectal adenocarcinoma. Conclusions This study implied that CD66a can function both as an epithelial cell adhesion protein or alternatively as secreted CD66a. In addition, a high expression of CD66a was significantly correlated with tumor invasion, stage, and pre-operation serum CEA level.     

Cyclooxygenase-2 Expression in Colorectal Adenomas

PURPOSE: Cyclooxygenase-2 is an important target for nonsteroidal anti-inflammatory drugs in suppressing colorectal tumorigenesis. To evaluate the role of cyclooxygenase-2 in sporadic colorectal adenoma, we correlated cyclooxygenase-2 expression in adenomas with other adenoma characteristics. METHODS: Cyclooxygenase-2 expression was evaluated immunohistochemically in 95 endoscopically resected colorectal adenomas. RESULTS: Cyclooxygenase-2 was expressed mainly in the cytoplasm of adenoma cells, where it was seen in 74 percent (70/95) of adenomas. Expression was related significantly to grade of dysplasia (P < 0.001) and tumor size (P = 0.028). Multivariate logistic regression analysis showed cyclooxygenase-2 expression in adenoma cells to be independently associated with grade of dysplasia (P = 0.001). CONCLUSION: Observed associations suggest that cyclooxygenase-2 plays an important role in progression of the adenoma-to-carcinoma sequence.     

Expression of proliferating cell nuclear antigen and CD44 variant exon 6 in primary tumors and corresponding lymph node metastases of colorectal carcinoma with Dukes＇＇ stage C or D

AIM: To study changes in characteristics of colorectal carcinoma during the metastatic process and to investigate the correlation between cell proliferation activity and metastatic ability of patients with Dukes′ stage C or D.METHODS: Formalin fixed and paraffin embedded materials of primary tumors and corresponding lymph node metastases resected from 56 patients with Dukes′ stage C or D of colorectal carcinoma were stained immunohistochemically with proliferating cell nuclear antigen (PCNA) and CD44variant exon 6 (CD44v6).RESULTS: Thirty-one of 56 patients (55.4 %) expressed PCNA in the primary sites and 36 of 56 patients (64.3 %)expressed PCNA in the metastatic lymph nodes. A significant relation in PCNA expression was observed between the primary site and the metastatic lymph node (0.010＜P＜0.025).Forty-one of 56 patients (73.2 %) expressed CD44v6 in the primary site and 39 of 56 patients (69.6 %) expressed CD44v6 in the metastatic lymph node. There was also an significant relationship of CD44v6 between the primary site and the metastatic lymph node (0.005＜P＜0.010). No difference was observed between expression of CD44v6 and PCNA in the primary site (0.250＜P＜0.500).CONCLUSION: This study partially demonstrates that tumor cells in metastatic lymph node of colorectal carcinoma still possess cell proliferation activity and metastatic ability of tumor cells in primary site. There may be no association between cell proliferation activity and metastatic ability in colorectal carcinoma.     

Potential Role of bcl-2 and Ki-67 Expression and Apoptosis in Colorectal Carcinoma: A Clinicopathologic Study

Colorectal cancer is associated with deregulation of apoptotic and proliferative processes. The purpose of this study was to investigate the presence of apoptosis and proliferation in colorectal cancer and evaluate their possible correlation with classic prognostic markers and patients' survival. Tumors from 117 patients, followed for 44–142 months, were studied immunohistochemically using the anti-bcl-2 and anti-Ki-67 antibodies. Apoptotic body index (ABI) was assessed by a standard TUNEL method. The bcl-2 protein was detected in 65% of adenocarcinomas with increased expression in low-grade and early-stage tumors. No association was noted between bcl-2 expression and proliferative activity, ABI, or patients' survival. A positive correlation was observed between ABI and proliferation (P < 0.05). Apoptosis was more frequently observed in advanced tumor stage or high-grade neoplasms. Cox analysis revealed that only tumor stage and grade constituted independent prognostic factors. The study suggests that there is a possible deregulation of the mechanisms that control bcl-2 expression in high-grade and advanced-stage colorectal carcinomas. Regulation of apoptosis is a complex phenomenon and other factors, including tumor heterogeneity, may be involved.     

Expression and clinical significance of CD44V5 and CD44V6 in resectable colorectal cancer

Purpose This study was conducted to evaluate the prognostic significance of CD44v5 and CD44v6 in resectable colorectal cancer.Materials and methods Membranous CD44v5 and CD44v6 levels were measured by an immunoenzymatic assay in tumors and surrounding mucosal samples obtained from 105 patients with resectable colorectal carcinomas.Results There were no significant differences of CD44v5 levels between tumors [median: 3.2 (range: 0.9–83.5) ng/mg protein) and surrounding mucosal samples (3 (3–146.2) ng/mg protein]. However, tumor samples showed significantly higher CD44v6 levels [19.5 (2.2–562.9) ng/mg protein] than mucosal samples [5 (5–230) ng/mg protein] (P=0.0001). Patients with higher CD44v5 or CD44v6 content in tumor samples had a considerably shorter relapse-free survival (P<0.05, for both). Patients with a higher CD44v6 content also had a shorter relapse-free and overall survival in the multivariate analysis (P<0.05).Conclusion The results of this study suggest a role of CD44v5 and CD44v6 in colorectal cancer progression. Membranous CD44v levels in primary tumors, measured by immunoenzymatic assay, may contribute to a more precise prognostic estimation in patients with resectable colorectal cancer.Supported by grants from ISCIII Red de Centros de Cancer RTICCC (C03/10) and Obra Social Cajastur     

Polyps with different grades of dysplasia and their distribution in the colorectum

BACKGROUND/AIMS: To determine the role of adenomatous polyps in the development of colorectal cancers, we examined the relationship between the distribution and polyps with different grades of dysplasia (low, high), or/and cancers in the colorectum. METHODOLOGY: The distribution of 527 polyps with low-grade dysplasia was compared with that of 121 polyps with high-grade dysplasia, and 10 colorectal cancer lesions with adenomatous polyps in 361 patients who underwent total colonoscopy. RESULTS: The distribution rate of polyps at the distal colon and rectum into polyps with high-grade dysplasia significantly increased in comparison to that into polyps with low-grade dysplasia, respectively (p<0.002). The percentage of polyps with high-grade dysplasia measuring >1 cm significantly increased in comparison to that with low-grade dysplasia measuring >1 cm (p<0.00001). In patients with both adenomatous polyps and colorectal cancers, the polyps with high-grade dysplasia at the distal sites of cancerous lesions increased significantly more than at the proximal sites of cancerous lesions (p<0.05). Polyps with high-grade dysplasia have malignant potentials to intermediate between polyps with low-grade dysplasia and colorectal cancers in our study. CONCLUSIONS: The different distributions of different grades thus suggested that polyps with different grades of dysplasia at various colorectal sites were found to have different malignant potentials for cancer development.     

Significance of immunohistochemical over-expression of CD44v6 as an indicator of malignant potential in esophageal squamous cell carcinoma

Purpose The aim of the current study was to find out a clinicopathologic significance of CD44v6 over-expression in esophageal squamous cell carcinoma (ESCC), which has not been elucidated fully.Methods Immunohistochemical expression of CD44v6 was examined for 81 ESCCs. Correlation of CD44 over-expression with the clinicopathologic features were investigated.Results Thirty-eight ESCCs (46.9%) had over-expression of CD44v6. The proportions of the incidence of lymph node metastasis (P=0.039), lymphatic permeation (P=0.003), and blood vessel invasion (P=0.037) in ESCCs with over-expression of CD44v6 were significantly higher than those in ESCCs without over-expression of CD44v6. The stage of the tumor in ESCCs with over-expression of CD44v6 was significantly more advanced (P=0.045). Survival rates of patients with ESCC with over-expression of CD44v6 were significantly worse (P=0.0005). Moreover, CD44v6 over-expression (P=0.048) as well as blood vessel invasion (P=0.014) and stage of the tumor (P=0.010) were factors independently associated with the unfavorable prognosis of the patients with ESCC.Conclusions Over-expression of CD44v6 can be an indicator of the malignant potential of ESCC.     

Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer

AIM: To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6,and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma,intraductal carcinoma of breast, and lung cancer.METHODS: Using tissue microarray by immuhistochemical (IHC) staining and in situ hybri-dization (ISH), we examined the expression levels of nm23mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer.RESULTS: The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P＞0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P＞0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P＜0.01; r = -4.93, P＜0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P＜0.05;P＜0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P＜0.01; r = 5.04, P＜0.01). CD44sand CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P＜0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (x2= 5.68, P＜0.05). The expressional level of nm23mRNA was closely related to the degree of cell differentiation (P＜0.05) and lymph node metastasis (P＜0.01), but the expression of nm23 gene was not related to sex, age, and type of histological classification (P＞0.05).CONCLUSION: Patients with overexpression of CD44s and CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate and invasion. In addition, overexpression of CD44v6 is closely related to the degree of cell differentiation. Detection of the three genes is able to provide a reliable index to evaluate the invasion and metastasis of tumor cells.     

The Immunohistochemical expression of endothelial cell differentiation gene-2 receptor in human colorectal adenomas

BACKGROUND/AIMS: The EDG-2 (endothelial cell differentiation gene-2) has been characterized as one of the high-affinity receptors of lysophosphatidic acid: an extracellular lipid mediator which can induce tumor progression. Recent studies have revealed that EDG-2 plays an important role in various pathological events including cell proliferation and tumor development. The investigation of EDG-2 is thus considered important for eliciting the mechanism of tumorigenesis. However, in colorectal tissue, the clinical significance of EDG-2 expression remains unclear. In the current study, we examined the immunohistochemical expression of EDG-2 in colorectal mucosa and adenoma, and clarified its relation with the clinicopathological features. METHODOLOGY: One hundred and sixty-one colorectal polyps were resected endoscopically or surgically at our institute from 2000 to 2001. According to the degree of dysplasia, adenomas were grouped into two categories: low-grade (mild or moderate dysplasia) and high-grade (severe dysplasia or carcinoma in situ). We investigated EDG-2 expression by immunohistochemistry. RESULTS: EDG-2 was expressed almost exclusively in the cytoplasm in colorectal normal mucosa and adenoma. EDG-2 expression in normal mucosa and adenoma was 8% and 76%, respectively. EDG-2 expression was increased in low-grade adenoma compared with that in normal mucosa (P < 0.001). EDG-2 expression was significantly greater in adenomas with larger diameters (P < 0.001). CONCLUSIONS: We demonstrated that EDG-2 expression was increased in the early stage of adenoma. A significant correlation between EDG-2 expression and the size of the adenomas suggests that EDG-2 may play an important role in the growth of these adenomas.     

Expression of CD44 variants in osteosarcoma

The standard form of CD44 (CD44H) is a transmembranous glycoprotein, widely distributed on a variety of human lymphoid cells, epithelial cells and tumours. CD44 has many variant forms, which are generated by alternative splicing. In recent years, CD44 has been reported to be related to the degree of tumour differentiation, tumour cell invasion, and metastasis. We investigated 44 tumour specimens in 39 patients with osteosarcoma immunochemically to analyse the expression of CD44 standard (CD44H) and variant exon-encoded gene products (CD44v3, v4, v5, v6, v7, v9, and v10). Furthermore, the relationship between CD44 expression and the clinical outcome of patients with osteosarcoma was analysed. Membrane accentuation and exclusive cytoplasmic reactivity were analysed as separate staining patterns. Tumour cells and some multinucleated giant cells were markedly stained. CD44H, v3, v4, v5, v6, v7, v9, and v10 were expressed in 85%, 49%, 54%, 59%, 46%, 5%, 28%, and 10% of the specimens respectively. The cumulative 5-year metastasis-free survival was 58% in CD44v6-negative cases and 24% in CD44v6-positive cases (P=0.046). However, the cumulative 5-year metastasis-free survival was not significantly different between cases positive and negative for other variants of CD44. Multivariate analysis (Cox proportional-hazard model) with CD44v6 expression (positive or negative), chemotherapy (intensive or non-intensive), tumour site (proximal or distal), and age (at least 30 years or less than 30 years) showed that expression of CD44v6 and chemotherapy were important prognostic factors in patients with osteosarcoma. Overexpression of CD44 isoforms containing variant v6 is correlated with poor prognosis in patients with osteosarcoma. Received: 4 March 1999 / Accepted: 7 June 1999     

Prospective Observation of Small Adenomas in Patients After Colorectal Cancer Surgery Through Magnification Chromocolonoscopy

Purpose This study was designed to confirm the safety of not removing small adenoma in patients who undergo colorectal cancer surgery. Methods Patients who underwent surveillance colonoscopy after surgery were enrolled. The study was approved by our institutional review board. Colonoscopy was performed with magnification chromocolonoscopy. Benign adenomas of 6 mm or less in size, diagnosed based on both nonmagnified and magnified observation, were left unresected with a maximum of three polyps per patient. The sites of the polyps were marked by tattooing. Interval colonoscopy was performed predominantly yearly or biennially. Increase in size by 2 mm or larger was defined as significant. In follow-up, polyps were removed if they grew larger than 6 mm, were suspicious for high-grade dysplasia, or the patients requested to have polyps removal. Results Five hundred polyps in 284 patients met the above criteria and were not resected, and 412 polyps were followed by repeat colonoscopy. The mean observation period was 3.6 ± 2.2 years and the mean number of repeat colonoscopy was 3.6 ± 1.6. At the final colonoscopy, 71 percent of 412 polyps showed no change in size, 15 percent increased, 3 percent decreased, and 11 percent could not be identified. Eighty-eight polyps were resected endoscopically, and histology showed neither cancer nor adenomas with high-grade dysplasia. Two hundred fifty-five polyps detected in the same patient cohort during index/repeat colonoscopy were removed, including four adenomas with high-grade dysplasia and two T1 cancers. Conclusions Leaving small polyps is safe even in patients who have undergone colorectal cancer surgery, provided that careful observation is guaranteed. Supported in part by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007.     

Immunohistochemical study of epithelial cell proliferation in hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel

A monoclonal antibody to bromodeoxyuridine was used in tissue specimens previously incubated with bromodeoxyuridine to show S-phase cells by immunohistochemical technique. Biopsy specimens of normal mucosa (n = 10), hyperplastic polyps (n = 10), adenomas with low-grade dysplasia (n = 20), adenomas with high-grade dysplasia (n = 10), and invasive adenocarcinomas (n = 10) of the large bowel were studied. Labeling index and cell proliferative patterns were analyzed. No statistically significant difference was found in labeling index between normal mucosa and hyperplastic polyps or between adenomas with high-grade dysplasia and adenocarcinomas. The labeling index was significantly lower in normal mucosa and in hyperplastic polyps than in adenomas and adenocarcinomas (p less than 0.001). The difference in labeling index between adenomas with high-grade dysplasia and low-grade dysplasia was also statistically significant (0.01 less than p less than 0.05). In normal mucosa and in hyperplastic polyps the proliferative zone was confined to the lower two-thirds of the crypt; no kinetic activity was found in the upper portions of the crypt or in surface epithelium. In adenomas the labeled cells were either present in the upper third or scattered along the whole axis of the crypt and in the surface epithelium. Labeling patterns in invasive carcinomas were similar to those observed in adenomas with high-grade dysplasia. The difference in proliferative patterns between hyperplastic polyps and adenomas supports a different significance of the two polypoid lesions in the histogenesis of large bowel cancer; our results confirm the subsequent steps of the adenoma-carcinoma sequence. Immunohistochemical labeling patterns observed with monoclonal antibody to bromodeoxyuridine in polypoid and cancer lesions of the large bowel are similar to those described by autoradiographic studies.     

Narrow-band imaging observation of colorectal lesions using NICE classification to avoid discarding significant lesions

AIM: To assess the risk of failing to detect diminutive and small colorectal cancers with the “resect and discard” policy.METHODS: Patients who received colonoscopy and polypectomy were recruited in the retrospective study. Probable histology of the polyps was predicted by six colonoscopists by the use of NICE classification. The incidence of diminutive and small colorectal cancers and their endoscopic features were assessed.RESULTS: In total, we found 681 cases of diminutive (1-5 mm) lesions in 402 patients and 197 cases of small (6-9 mm) lesions in 151 patients. Based on pathology of the diminutive and small polyps, 105 and 18 were non-neoplastic polyps, 557 and 154 were low-grade adenomas, 18 and 24 were high-grade adenomas or intramucosal/submucosal (SM) scanty invasive carcinomas, 1 and 1 were SM-d carcinoma, respectively. The endoscopic features of invasive cancer were classified as NICE type 3 endoscopically.CONCLUSION: The risk of failing to detect diminutive and small colorectal invasive cancer with the “resect and discard” strategy might be avoided through the use of narrow-band imaging observation with the NICE classification scheme and magnifying endoscopy.     

肝细胞癌CD44v6和p16基因蛋白的表达及其意义

目的探讨CD44v6和p16基因蛋白表达与肝细胞癌(HCC)转移和预后的关系。方法应用免疫组织化学方法,检测分析110例HCC组织中CD44v6及p116蛋白表达,结合随访资料分析。结果在HCC中,CD44v6和p16阳性表达率分别为42.7%和34.5%。CD44v6阳性表达的HCC转移率高(P<0.05),分化程度和患者>5年生存率低(P<0.05);p16阳性表达的HCC转移率低(P<0.05),分化程度和患者>5年生存率高(P<0.05)。CD44v6与p16表达呈负相关(r=-0.59,P<0.005)。结论CD44v6和p16表达与HCC转移和患者生存期密切相关,检测CD44v6和p16蛋白的表达可作为判断HCC预后的参考指标。     

Colorectal Polyps in Carriers of the APC I1307K Polymorphism

PURPOSE The probability of colorectal cancer is moderately increased among carriers of the APC I1307K polymorphism. However, it is not known if endoscopic surveillance of this high-risk group is warranted. The prevalence of polyps and adenomas in specimens of colorectal cancer who are carriers and noncarriers of the APC I1307K polymorphism is compared. METHOD Prevalence of adenomatous polyps in the pathology specimens of the study participants, stratified by their APC I1307K polymorphism status, was studied in 900 consecutive cases of colorectal cancer diagnosed in northern Israel between 1998 and 2002, within the framework of a population-based, case-controlled study (MECC Study). RESULTS The APC I1307K mutation was detected in 78 colorectal cancer cases (8.7 percent) of the study population. Prevalence was higher among Ashkenazi Jews (11.2 percent) than among non-Ashkenazi Jews (2.7 percent) or Arabs (3.1 percent). After adjustment for age, APC I1307K carriers were significantly more likely than noncarriers to have polyps in their surgical specimen (51.3 percent vs. 32.6 percent, P = 0.002). Adenomas with a tubular component (either tubular adenomas or tubulovillous adenomas), but not villous adenomas, were significantly more frequent among carriers (37.2 percent vs. 23.6 percent, P = 0.005). CONCLUSION Together with former evidence of I1307K being a risk factor for colorectal cancer, these data suggest that colonoscopic surveillance for colorectal adenomas and cancer may be warranted in I1307K carriers, even in the absence of other identifiable risk factors. Supported by the National Institutes of Health grant RO1-CA81488 to S.B.G. and G.R.     

大肠癌组织RAB5A和CD44v9表达的意义

目的:探讨大肠癌组织RAB5A和CD44v9表达的意义．方法:应用SP免疫组化法检测43例大肠癌病理蜡块中RAB5A和CD44v9的蛋白质表达;取 60例大肠癌患者新鲜组织标本,提取RNA并逆转录合成cDNA,应用Real-time PCR法检测组织样本中RAB5A和CD44v9的基因表达;分析CD44v9和RAB5A的基因与蛋白质表达量与大肠癌分化及转移程度的相关性．结果:RAB5A蛋白表达阳性率为100％,阳性表达位于胞质和胞膜;CD44v9表达阳性率为 86．7％,阳性表达位于胞质;荧光定量PCR结果经熔解曲线分析各样本扩增产物的Tm值一致并与阳性对照的Tm值吻合．RAB5A cDNA 的表达量在高分化和中分化大肠癌组织中低于低分化大肠癌组织(P<0．01),在无淋巴结转移的大肠癌组织中低于有淋巴结转移的组织(P<0．01),而CD44v9 cDNA的表达趋势与 RAB5A相同;RAB5A与CD44v9的蛋白和基因表达均呈正相关(x2=14．532,P<0．01)．结论:RAB5A和CD44v9的表达与大肠癌的分化和转移有关,可能在跨膜信号传导和基质侵袭中共同发挥作用．     

Mutation of p53 tumor suppressor gene in flat neoplastic lesions of the colorectal mucosa

PURPOSE: In a recent comparative histologic survey of flat colorectal neoplasias, we found more lesions with highgrade dysplasia (HGD) and carcinoma in Japanese than in Swedish patients. The purpose of this work was to assess the p53 protein overexpression in flat colorectal neoplasias in Swedish patients and to compare results with those reported in Japan. METHOD: A total of 57 neoplastic lesions of the colorectal mucosa were investigated: 29 had been regarded both at endoscopy and at histology as flat and the remaining 28 as exophytic. Deparaffinized, rehydrated sections were treated immunohistochemically to detect the p53 protein. Lesions having a moderate (++) or high (+ + +) staining were considered as overexpressing the p53 protein. RESULTS: Results indicated that 16.7 percent (1/6) of the exophytic adenomas with low-grade dysplasia (LGD) had distinct p53 overexpression as well as 57.1 percent (8/14) of those with HGD and 87.5 percent(7/8) with invasive growth. In flat neoplastic lesions, 7.7 percent (1/13) of the tubular adenomas with LGD, 25 percent (3/12) of tubular adenomas with HGD, and 75 percent (3/4) of adenocarcinomas arising in flat adenomas had p53 overexpression. CONCLUSIONS: In Swedish patients, the proportion of flat and exophytic colorectal neoplasias showing p53 immunoreactivity increased with increasing degree of dysplasia, the highest percent being recorded in lesions with invasive growth. Because a similar stepwise increase was reported for exophytic and flat colorectal neoplasias in Japan, it seems that the comparison of results in both countries is justifiable. One possible conclusion from this comparison is that the higher proportion of flat neoplastic colorectal lesions with HGD and carcinoma in the Japanese (compared with the Swedish) takes place for reasons extraneous to the overexpression of the p53 protein.Supported by grants from the the Cancer Society, Stockholm, and the Karolinska Institute.