Sialyl Tn antigen expression is associated with the prognosis of patients with advanced colorectal cancer

BACKGROUND/AIMS: One of the main problems in multimodal cancer treatment is the lack of prognostic parameters for the individual patient. This study was conducted to clarify the prognostic factors in patients with advanced colorectal cancer. METHODOLOGY: We examined DNA ploidy, Ki-67-derived growth fraction and the expression of CA 19-9, Sialyl Tn (STN) and carcinoembryonic antigens (CEA), along with standard clinicopathological variables including age, sex, tumor location, tumor size, cell differentiation, depth of invasion, and lymph node metastasis in 78 patients with advanced colorectal carcinoma, who underwent curative surgical resection. In addition, we determined the prognostic significance of these parameters. RESULTS: Forty-six patients (59.0%) showed aneuploidy and 32 (41.0%) showed diploidy. The Ki-67 labeling index ranged from 13.9-40.3% with a mean of 24.9%. The index was not correlated with standard clinicopathological variables. There was no significant correlation between seropositive rates for CEA, CA 19-9, or STN and standard clinicopathological variables except for age. In tumor tissue, the positive rates for these antigens were 62.8% for CA 19-9, 67.1% for STN, and 96.2% for CEA. There was no significant correlation between positive rates and clinicopathological variables. The expression of STN in serum had the strongest association with survival, followed by lymph node metastasis and expression of STN in tissue. CONCLUSIONS: We conclude that not only lymph node metastasis but also STN expression are important prognostic factors in patients with advanced colorectal carcinoma who undergo curative surgical resection.     

CD44 expression in benign and malignant colorectal polyps

PURPOSE: This retrospective study was undertaken to evaluate immunohistochemically the expression of CD44 standard protein and CD44v5 and CD44v6 isoforms in colorectal adenomas and early invasive cancers developing within adenomas as possible markers characterizing colorectal polyps with a more aggressive biologic potential. METHODS: Archival tissues of 81 consecutive locally resected colorectal polyps, comprising 57 colorectal adenomas and 24 carcinomas-in-adenomas, were stained immunohistochemically with the use of commercially available mouse monoclonal antibodies: SFF-2 for CD44 standard protein, VFF-8 for CD44v5, and VFF-7 for CD44v6. RESULTS: Sixtythree percent of the colorectal polyps were positive for CD44 standard protein, 59 percent were positive for CD44v5, and 27 percent were positive for CD44v6. Ninetythree percent of the low-grade adenomas were CD44 standard protein-positive, in contrast to 50 percent of the high-grade adenomas and only 42 percent of the carcinomas-in-adenomas (Kendall's Tau =–0.42;P<0.0001). CD44v6 expression was more frequently found in early invasive cancers (54 percent) than in high-grade adenomas (25 percent) and low-grade adenomas (7 percent). This difference also was statistically significant (Kendall's Tau-b =0.39;P=0.00003). Surprisingly, a downregulation of CD44 standard protein expression was observed in the adenoma tissue adjacent to carcinomas (62 percent) and areas with high-grade atypia (71 percent), compared with low-grade adenomas (93 percent; Kendall's Tau-b =–0.28;P=0.004). CONCLUSIONS: Our data suggest that CD44 standard protein and CD44 isoform v6 expression differs considerably in benign and malignant colorectal polyps. Clinical studies with larger patient groups could clarify the prognostic potential of CD44 further     

Treatment patterns and costs associated with sessile colorectal polyps

OBJECTIVES: Because of the paucity of existing literature on treatment and costs associated with sessile lesions, the objectives of this study were to perform a retrospective analysis on patients with sessile polyps to identify patient and polyp characteristics, to determine treatment patterns, and to estimate the cost of treating these patients. METHODS: We conducted a retrospective, observational cohort study of 280 patients who presented to a large teaching hospital between 1997 and 2000 with at least one sessile or broad-based pedunculated colorectal polyp of any size or histology, not including adenocarcinoma greater than stage T1. RESULTS: Mean polyp size was 1.3 cm, and two thirds of polyps were removed in a single procedure. The number of repeat procedures increased with polyp size (Kendall T-b = 0.47; 95% CI = 0.39-0.55). Patients with polyps > or = 2 cm were 5.88 times more likely than patients with smaller polyps to undergo a surgical procedure. Surgical procedures required 88.01 min longer than nonsurgical procedures (95% CI = 74.43-102.42). Mean total cost of treatment was $2,038 (range $153 to $14,838). Open resection ($6,165) was the most costly surgical procedure, and piecemeal polypectomy ($892) was the most costly nonsurgical therapeutic procedure. CONCLUSIONS: One third of polyps required more than one procedure. Surgical procedures accounted for the majority of resource use in this sample. Finally, patients with polyps > or = 2 cm incurred almost half the total costs while accounting for only 22% of the sample. The greatest economic gains could be made by improving efficiency of polyp removal for these patients.     

HLA-DR抗原在大肠癌组织中的表达

目的 观察HLA-DR抗原在大肠癌组织中表达及其与临床病理的关系。 方法 用免疫组织化学ABC法检测30例正常大肠组织和92例大肠癌组织中HLA-DR抗原表达。 结果 正常大肠组织无HLA-DR表达,27例大肠癌组织中有HLA-DR表达,阳性率为29.4％。HLA-DR抗原在Dukes'A,B,C期大肠癌的表达率分别为23.5,30.3％和31.0％(P>0.05);HLA-DR抗原在高、中和低分化大肠癌组织中的表达率分别为44.4％,27.4％和28.6％(P>0.05)。 结论 大肠癌组织中有HLA-DR抗原表达,其表达与大肠癌Dukes分期及细胞分化程度无关。     

Different expressions of sialyl Tn antigen between polypoid and flat-type early colorectal cancers

PURPOSE: Sialyl Tn (STn) antigen is a cancer-associated carbohydrate antigen expressed in cancers of the digestive tract. We compared the proportion of specimens of flat-type colorectal cancers expressing STn with that of polypoid cancers, by examining the immunohistochemical reactivity of STn in various morphologic types of early and advanced colorectal cancers. METHODS; A total of 111 biopsies from the colorectal area were examined for STn expression, including 11 adenomas, 58 early cancers, and 42 advanced cancers. Each section was stained immunohistochemically for STn antigen. In each section, we examined STn expression in the cancer area, adjacent mucosa, and normal epithelium. RESULTS: STn expression was detected in 90.9 percent of adenomas, 36.2 percent of early cancers (T1), 64.3 percent of advanced cancers (>T1), and 52 percent of mucosa adjacent to cancer. The morphology of cancer tissue did not influence the number of specimens exhibiting STn antigen expression in mucosa adjacent to cancer cells. STn antigen was rarely expressed in flat or depressed-type early cancers (T1; 7.1 percent), and the expression was higher in moderately than in well-differentiated adenocarcinomas. In advanced cancers (>T1), a similar proportion of protruding and small ulcerative cancers expressed STn. CONCLUSION: Our results suggest that the low expression of STn antigen in flat-type cancers may be the result of different mechanisms of cellular transformation during carcinogenesis from the usual adenoma-carcinoma sequence in colorectal neoplasms.     

The relationship between circulating sialyl Tn antigen and polypoid or nonpolypoid growth characteristics in colorectal cancer

Recent studies delineated two different patterns of tumor growth in colorectal carcinoma characterized as polypoid and nonpolypoid (PG-type and NPG-type, respectively). We quantified serum sialyl Lewis (Le)^a (CA19–9), sialyl Le^x (SLX), sialyl Tn (STN), and carcinoembryonic antigen (CEA) in 269 colorectal cancer patients to establish whether their levels correlated with any biological or clinical differences between PG-type and NPG-type cancer. Patients were divided into high and low antigen groups (higher or lower than a selected diagnostic-based cut-off value) and compared. Statistical testing was by univariate and multivariate (logistic regression) analyses. Forty-seven (17.5%) patients with PG-type and 222 (82.5%) with NPG-type cancer were studied. In contrast to NPG-type, the characteristics of the PG-type cancers included a low rate of lymph node metastasis and a high serum STN level. In contrast to a low STN level, a high STN level was independently related to the presence of distant metastasis in patients with PG-type cancer, and also to the presence of distant metastasis and large-sized tumor in patients with NPG-type cancer. These data suggest that differences in STN levels in the serum of patients with PG-type or NPG-type colorectal carcinomas may be at least partly responsible for different tumor progression behavior. Received: 17 December 1999 / Accepted: 6 March 2000     

Increased expression of urokinase-type plasminogen activator in colorectal carcinoma and in adenomatous polyps

Human plasminogen activators (HPA) comprise the tissue type produced mainly by endothelial cells of 66 000 molecular weight (MW) which is principally involved in fibrinolysis (HPA66) and the urokinase type of 52 000 MW (HPA52) which is implicated in the invasion process of malignancy. The purpose of this study was to elucidate the pattern of HPA expression in histologically normal colonic mucosa, sporadic polyps, polyposis coli polyps, and in colon cancer tissue, to determine whether the expression of HPA52 is a correlate of neoplastic transformation of colonic epithelial cells. Homogenates of colonoscopic biopsies and resected colon tissue were subjected to polyacrylamide gel electrophoresis and the HPA activity was detected by a fibrin overlay gel. In histologically normal mucosal biopsies from non-cancer-bearing colons and in uninvolved mucosa from cancer-bearing colons, only HPA66 was detected. By contrast, all 19 colon cancer specimens expressed HPA52 and 16 of these also showed HPA66 activity. Two of three colon cancer cell lines showed HPA52 activity, but none expressed HPA66. HPA52 activity was observed in 17 of 20 adenomatous polyps, all of which displayed HPA66 activity. No correlation was found between polyp size, degree of epithelial dysplasia or the type of polyp architecture, and the semiquantitative estimates of HPA52 activity as judged by the areas of fibrinolysis generated.
This study of HPA52 in the colon epithelial neoplasms comprising adenomatous polyps, colon cancer tissue and colon cancer cell lines suggests that the transformation of the colon epithelial cell correlates with increased expression of HPA52, an enzyme that has been implicated in the invasive process of malignancy.     

Endoscopic resection of large colorectal polyps.

BACKGROUNDS: Endoscopic polypectomy is a common technique, but there are discrepancies over which treatment--surgical or endoscopic--to follow in case of polyps of 2 cm or larger. OBJECTIVES: To analyse the efficacy and complications of colonoscopic polypectomy of large colorectal polyps. PATIENTS AND METHODS: 147 polypectomies were performed on 142 patients over an eight-year period. The technique used was that of submucosal adrenaline 1:10000 or saline injection at the base of the polyp, followed by resection of the polyp using a diathermic snare in the smallest number of fragments. Remnant adenomatous tissue was fulgurated with an argon plasma coagulator. Lately, prophylactic hemoclips have been used for thick-pedicle polyps. Complete removal was defined as when a polyp was completely resected in one or more polypectomy sessions. Polypectomy failure was defined as when a polyp could not be completely resected or contained an invasive carcinoma. RESULTS: The mean patient age was 67.9 years (range, 4-90 years), with 68 men and 79 women. There were 74 sessile polyps, and the most common location was the sigmoid colon. The most frequent histology was tubulovillous. Most of the polyps (96.6%), were resected and cured. This was not achieved in four cases of invasive carcinoma, and a villous polyp of the cecum. All pedunculated polyps were resected in one session, whereas the average number of colonoscopies for sessile polyps was 1.35 +/- 0.6 (range, 1-4). The polypectomy was curative in all of the in situ carcinomata except one. As for complications, 2 colonic perforations (requiring surgery) and 8 hemorrhages appeared, which were controlled via endoscopy. There was no associated mortality. CONCLUSIONS: Endoscopic polypectomy of large polyps (> or =2 cm) is a safe, effective treatment, though it is not free from complications. Complete resection is achieved in a high percentage, and there are few relapses. It should be considered a technique of choice for this type of polyp, except in cases of invasive carcinoma.     

Mucin core protein expression by colorectal mucinous carcinomas with or without mucus hyperplasia

Background In the categorization of colorectal mucinous carcinomas, much attention has been paid to the amount of extracellular mucin, but little to that of intracellular mucin. Perhaps this factor would be useful in further categorization.Methods We estimated the amount of intracellular mucin morphologically, and classified colorectal tumors (tubular adenomas, mucinous carcinomas, and nonmucinous carcinomas) into two categories each, those with and without intracellular mucus hyperplasia. From preliminary results, we chose a range of 50% or more for the ratio of intracellular mucus to the total area of tumor cells for our definition of such hyperplasia. Then, mucin expression in the different categories was examined immunochemically with antibodies to the mucin core proteins MUC1, MUC2, MUC5AC, and MUC6.Results MUC1 expression was found in none of the 40 adenomas, 8 (17%) of the 48 mucinous carcinomas (with little difference in those with and without mucus hyperplasia), and 4 (16%) of the 25 nonmucinous carcinomas. MUC2 was found in all mucinous carcinomas. MUC5AC was found in 18 (86%) of the 21 mucinous carcinomas with mucus hyperplasia and 18 (90%) of the 20 adenomas with mucus hyperplasia, but in only 9 (33%) of the 27 mucinous carcinomas without mucus hyperplasia, 5 (20%) of the 25 nonmucinous carcinomas, and 2 (10%) of the 20 adenomas without mucus hyperplasia.Conclusions Mucinous carcinomas with and without mucus hyperplasia may arise from adenomas with and without mucus hyperplasia, respectively. The amount of intracellular mucin may be a morphologic reflection of the origin of colorectal mucinous carcinomas.     

Comparison of cyclo-oxygenase 2 expression in colorectal serrated adenomas to expression in tubular adenomas and hyperplastic polyps

BACKGROUND AND AIMS: Serrated adenoma (SA) is a newly defined category of colorectal neoplasia that contains features of both adenoma and hyperplastic polyp, and has two patterns, hyperplastic and cerebriform patterns. Since cyclooxygenase 2 (COX-2) has been found upregulated in colorectal cancers and adenomas, we examined whether either the hyperplastic or cerebriform pattern of SA has the potential for tumor progression and should be a target for clinical treatment. PATIENTS AND METHODS: An immunohistochemical scoring system was used to compare COX-2 expression in colorectal SAs (n=79), tubular adenomas (n=66), and hyperplastic polyps (n=21). RESULTS: COX-2 scores were significantly higher in SA of the cerebriform pattern (n=44) than in SA of the hyperplastic pattern (n=35). There was no difference in COX-2 scores between SA of the cerebriform pattern and tubular adenoma. In SA accompanied by hyperplastic polyp (n=26) the hyperplastic components expressed little COX-2, the same as traditional hyperplastic polyps. COX-2 expression in the SA component was similar to that in pure SA. CONCLUSION: SA of the cerebriform pattern should be treated similarly as traditional tubular adenomas. COX-2 induction may additionally be involved in progression from hyperplastic polyp to SA.     

Reliability of in situ measurements of colorectal polyps.

A reliable and sensitive in situ method for measuring polyp size is fundamental for growth studies of colonic polyps. A measuring probe inserted through a colonoscope can give a visual assessment of polyp diameter, and from a picture of the polyp the area of the polyp on the picture can be calculated by computerized analysis. To test the reliability and sensitivity of these two in situ measurements, 43 colonic polyps (mean diameter, 8.5 mm; range, 4-20 mm) removed by snare diathermy resection were examined. The maximal diameter was measured, and two Polaroid pictures taken of each polyp. After polypectomy each polyp was subjected to extracorporeal reassessment of diameter and measurement of weight and volume. By computerized analysis of the pictures the following variables were estimated: 1) area of the polyp on the picture; 2) largest diameter; 3) maximum width 90 degrees on the largest diameter; 4) maximum distance from centre of gravity; and 5) minimum distance from centre of gravity. Results showed good correlation between diameter measured in situ and after removal (r = 0.93), diameter raised to the 3rd power and weight (r = 0.93), and also to volume (r = 0.77). Area analysis compared with weight was less good (r = 0.72). A very high correlation was demonstrated between weight and volume (r = 0.99). We conclude that the measurement of diameter in situ with a measuring probe is sensitive and somewhat more reliable than computerized analysis of size. The present 3-year follow-up and intervention study will show which of the two methods is preferable for evaluation of polyp growth.     

Alcohol consumption in patients with colorectal adenomatous polyps.

The risk of developing colorectal adenomatous polyps is probably increased by a variety of dietary and environmental factors. We found an association with current alcohol and cigarette consumption. The risk of polyps was increased three times in drinkers who did not smoke and two times in smokers who did not drink, with those who both drank and smoked having 12 times the risk of total abstainers. Since colonic adenomatous polyps are generally regarded as premalignant lesions, these results lend support to the view that alcohol consumption may be an important factor in the pathogenesis of colorectal neoplasia, thus reinforcing the proposed polyp/carcinoma sequence in colorectal carcinogenesis. The role of smoking, however, is less clear particularly since the lack of association of colorectal carcinoma and smoking has been reported in many other studies.     

Mixed colorectal polyps. An immunohistologic and mucin-histochemical study

The morphology of mixed colorectal polyps was analysed. Thirteen such polyps were found out of 2700 colorectal polyps (0.5%). Histology showed a spectrum of hyperplastic crypts from almost pure goblet cell population (two polyps) to hypermature serrated epithelium with scanty goblet cells (seven polyps). Tubular adenomas occurred in 12 polyps, and a tubulovillous adenoma was found in the largest polyp. Moderate dysplasia was seen in the five large polyps. The border between neoplastic and hyperplastic cells was usually sharp. Mucin histochemistry showed similarities between the mixed polyps and colorectal carcinomas--namely, the reduction/absence of sialomucin in both mature hyperplastic crypts and adenomatous glands. The expression of carcinoembryonic antigen within the hyperplastic crypts and within the neoplastic crypts showing moderate dysplasia was similar to that seen in colorectal carcinomas, whereas it was normal within the neoplastic crypts with low-grade dysplasia. IgA was reduced or absent in both components. Blood group antigen was found only within the adenomatous component of the largest polyp showing also moderate dysplasia.     

Barrett食管粘蛋白表达及意义

目的检测Barrett食管中粘蛋白的表达，探讨粘蛋白表达的意义。方法采用免疫组化方法检测Barrett食管上皮中MUC1、MUC2、MUC3、MUC5AC及MUC6粘蛋白的表达，分析粘蛋白表达与Barrett食管组织病理学分型及放大内镜下小凹分型间的关系。结果Barrett食管胃型化生上皮以及肠化上皮均可见MUC1的弱阳性表达；肠化上皮中见MUC2的强阳性表达，阳性表达主要位于杯状细胞胞浆中；MUC3不仅在Barrett食管肠化上皮表层的柱状细胞及杯状细胞浆表达，而且在肠化上皮的无肠化区的柱状细胞内也可见阳性表达；MUC5AC不仅在Barrett食管胃、肠上皮化生的表层柱状上皮胞浆内强阳性表达，而且在杯状细胞亦见阳性表达；在Barrett食管胃、肠两型上皮化生的深层腺体均可见MUC6的阳性表达，抗原定位于细胞浆内，杯状和柱状细胞均有阳性反应物质；在不同分型小凹中，绒毛状及不规则型小凹上皮MUC2、MUC3的阳性表达显著高于点状和棒状（P〈0．01）；MUC2、MUC3仅在肠化上皮中表达，在胃底及交界型上皮中无表达；MUC1、MUCSAC及MUC6在胃型及肠型化生上皮中均呈阳性表达，阳性表达率在各组织病理分型间差异无统计学意义（P〉0．05）。结论Barrett食管肠化生上皮中特异表达MUC2与MUC3；MUC3的表达可能是肠化形成的早期事件；绒毛状及不规则型小凹中MUC2与MUC3高表达提示两型小凹的肠型分化特点，检测其表达有助于Barrett食管特殊肠上皮化生的识别。     

Micronucleus analysis in patients with colorectal adenocarcinoma and colorectal polyps

AIM： To determine, by counting micronucleus （MN） frequencies, whether chromosomal or DNA damage have an effect on the pathogenesis of early colorectal adenocarcinoma （CRC）. METHODS： We analyzed MN frequencies in 21 patients with CRC, 24 patients with colon polyps [10 neoplastic polyps （NP） and 14 non-neoplastic polyps （NNP）] and 20 normal controls. RESULTS： MN frequency was significantly increased in CRC patients and in NP patients compared with controls （3.72 ± 1.34, 3.58± 1.21 vs 1.97 ± 0.81, P 〈 0.001）. However, there was no difference in the MN frequency between CRC patients and NP patients （P 〉 0.05）. Similarly, there was no difference in the MN frequency between NNP patients （2.06 ±0.85） and controls （P 〉 0.05）. CONCLUSION： Our results suggest increased chromosome/DNA instabilities may be associated with the pathogenesis of early CRC.