Relationship between intracellular localization of p34<Superscript>cdc2</Superscript> protein and differentiation of esophageal squamous cell carcinoma

Purpose G2/M cyclins including cyclins A and B can exert their biologic functions of mitosis and proliferation of the tumor cells by being combined by protein kinase p34cdc2. The aim of the current study was to elucidate the clinicopathologic significance of immunohistochemical expression of p34^cdc2 in esophageal squamous cell carcinoma (ESCC), which has not been resolved.Methods Immunohistochemical expression of p34^cdc2 was examined for 91 cases of ESCC, and the relationship between the type of p34^cdc2 expression and the clinicopathologic features of the patients and tumors was analyzed.Results Forty-one ESCCs demonstrated cytoplasm dominant expression of p34^cdc2 and the other 50 ESCCs showed nuclei dominant p34^cdc2 expression. This differential expression pattern of p34^cdc2 did not reflect a prognostic aspect; however, the proportion of keratinizing tumors ESCCs with cytoplasm dominant expression of p34^cdc2 was significantly higher than that among ESCCs presenting nuclei-dominant p34^cdc2 expression (P=0.006).Conclusion Cellular differentiation in squamous cell carcinoma of the esophagus may be mediated by an intracellular localization of p34^cdc2.     

Survival Stratification Panel of Colorectal Carcinoma with Combined Expression of Carcinoembryonic Antigen,Matrix Metalloproteinases-2, and p27<Superscript>kip1</Superscript>

Purpose The prognosis varies greatly in colorectal carcinoma patients, even in the same stage. We examined the association between the expression of matrix metalloproteinases-2, carcinoembryonic antigen, p27^kip1, and clinicopathologic features in patients with colorectal carcinoma to identify a possible panel of tumor markers in predicting prognosis of colorectal carcinoma. Methods The expressions of three individual markers in 127 colorectal carcinoma cases were analyzed by immunohistochemistry method. Univariate and multivariate analysis were performed to analyze the expression with the disease-free survival time in colorectal carcinoma. Results High expression of matrix metalloproteinases-2, carcinoembryonic antigen, and low expression of p27^kip1 were related to poor prognosis in univariate analysis (P = 0.0002; P < 0.0001; P = 0.0008). The expression of matrix metalloproteinases-2, carcinoembryonic antigen, p27^kip1, and tumor differentiation were independent prognostic factors for disease-free survival by Cox regression analysis. The coexpression panel of matrix metalloproteinases-2, carcinoembryonic antigen, and p27^kip had significant prognostic value in all patients (P_AB = 0.0103; P_BC = 0.0068; P_CD = 0.0117). Multivariate analysis with Cox regression reveals that coexpression of matrix metalloproteinases-2, carcinoembryonic antigen, and p27^kip1 were independent prognostic factors as tumor differentiation in colorectal carcinoma. In different stages, coexpression tumor markers functioned in Stages II and III but not in the 19 cases of Stage I. The reason might be the number of patients was too small. Conclusions The results of this study provided further evidence that the combination of tumor markers of matrix metalloproteinases-2, carcinoembryonic antigen, and p27^kip1 was more informative than any single tumor marker alone for the disease-free survival stratification of colorectal carcinoma. Coexpression of matrix metalloproteinases-2, carcinoembryonic antigen, and p27^kip1 might be a useful survival stratification panel for clinical management. Supported by the Research fund of the Beijing Municipal Science & Technology Commission (Grant H020920030390); Beijing New Star Project on Science & Technology (Grant 2006B55). Poster presentation at Digestive Disease Week, Los Angeles, California, May 20 to 25, 2006.     

Nuclear to cytoplasmic shift of p33<Superscript>ING1b</Superscript> protein from normal oral mucosa to oral squamous cell carcinoma in relation to clinicopathological variables

Purpose p33^ING1b, as a candidate tumour suppressor gene, has been found to be expressed a proportion of oral squamous cell carcinomas (OSCCs), however, its clinicopathological significance is not studied yet. Our aim was to investigate association of p33^ING1b expression with clinicopathological variables and particularly interesting new cysteine–histidine rich protein (PINCH) in OSCCs. Methods p33^ING1b expression was immumohistochemically examined in 20 normal oral mucosa specimens and 49 OSCCs. Results Normal squamous cells showed only p33^ING1b nuclear expression (no cytoplasmic expression), with a rate of 90% positive cases. While 24% of OSCCs appeared cytoplasmic expression (11 of them with weak nuclear staining) and the rest tumours (76%) were negative for p33^ING1b. Furthermore, the cases having lymph node metastasis showed a higher frequency of positive cytoplasmic expression than those without metastasis (P = 0.03). The p33^ING1b cytoplasmic expression was positively related to PINCH expression (P = 0.04), the cases positive for both proteins had a high rate of the metastasis (P = 0.03). Conclusions The transfer of p33^ING1b protein from the nucleus to the cytoplasm may result in loss of normal cellular function of the protein, which might play a role in the tumourigenesis and metastasis of OSCCs.     

Flow cytometric examination of p53 protein in primary tumors and metastases to the liver and lymph nodes of colorectal cancer

PURPOSE AND METHODS: To confirm prognostic significance of overexpression of p53 in cases of colorectal cancer, expression of p53 protein was examined by flow cytometry in 113 cases of colorectal cancer and its metastasis to the liver and lymph nodes. RESULTS: Overexpression of p53 was found in 44 (39 percent) of the 113 primary tumors. There were no significant correlations among the level of p53 protein in the primary tumor, clinicopathologic features, and prognosis of colorectal cancer. Overexpression of p53 protein was detected in 72 percent (18/25) of liver metastases and in 40 percent (10/25) of lymph node métastases. Frequency of samples that were positive for p53 was significantly higher for liver metastases than for primary tumors and lymph node metastases (P<0.01). By comparing overexpression of p53 in primary tumors with that in corresponding secondary tumors, a decrease of more than 5 percent in the fluorescence index, compared with primary tumor, was not found in liver metastasis but was found in 20 percent of lymph node metastases. Incidence of cases with lower level expression of p53, compared with primary tumor, was significantly higher in lymph node metastases (32 percent) than in liver metastases (8 percent;P<0.05). CONCLUSIONS: From these results, it seems possible that overexpression of p53 may not be a good prognostic indicator of colorectal cancer and may be influenced by environments of the tumor.Presented at the meeting of the Japanese Gastroenterological Surgery, Fukui City, Japan, July 20 and 21, 1995.     

Evaluation of Tumor Cell Dissociation as a Predictive Marker of Lymph Node Metastasis in Submucosal Invasive Colorectal Carcinoma

PURPOSE Tumor cell dissociation—the histologic finding of small solid carcinoma cell clusters and groups of dissociated dedifferentiated carcinoma cells at the invasive front–is related to tumor metastasis and patient prognosis. However, few previous reports have examined tumor cell dissociation in submucosal invasive colorectal carcinoma. We investigated the relation between tumor cell dissociation and lymph node metastasis in submucosal invasive colorectal carcinoma. We also examined immunohistochemical expression of E-cadherin and beta-catenin in submucosal invasive colorectal carcinoma.METHODS Submucosal invasive colorectal carcinoma tissue samples from 20 patients with lymph node metastasis and 100 patients without lymph node metastasis were evaluated. Sections stained with hematoxylin and eosin were evaluated for tumor cell dissociation. Immunohistochemistry was used to determine the expression and cellular distribution of E-cadherin and beta-catenin.RESULTS Tumor cell dissociation was more frequently identified in submucosal invasive colorectal carcinoma cases with lymph node metastasis than in those without lymph node metastasis (P = 0.0001). Decreased membranous expression of E-cadherin occurred more frequently in submucosal invasive colorectal carcinoma cases with lymph node metastasis than in those without lymph node metastasis (P = 0.025). Nuclear expression of beta-catenin tended to be present in submucosal invasive colorectal carcinoma cases with lymph node metastasis (P = 0.063). Decreased membranous expression of E-cadherin occurred more frequently in submucosal invasive colorectal carcinoma cases with tumor cell dissociation than in those without tumor cell dissociation (P = 0.0023).CONCLUSIONS Our results suggest that there is a relation between tumor cell dissociation and lymph node metastasis in submucosal invasive colorectal carcinoma. Tumor cell dissociation formation might be related to abnormal expression patterns of E-cadherin and beta-catenin in submucosal invasive colorectal carcinoma. Tumor cell dissociation and decreased membranous expression of E-cadherin would be important predictive markers for lymph node metastasis in submucosal invasive colorectal carcinoma.Presented at the 93rd Japanese Society of Pathology, Sapporo, Japan, June 9 to 11, 2004.     

<Emphasis Type="Italic">p16</Emphasis><Superscript><Emphasis Type="Italic">INK4A</Emphasis></Superscript> Alterations are accompanied by aberrant protein immunostaining in endometrial carcinomas

Purpose To date, the significance of p16^INK4A tumor suppressor gene inactivation in sporadic endometrial cancer (EC) has only rarely been described. In this study, we examined the alteration type and frequency of gene alterations [point mutations, aberrant promoter methylation and loss of heterozygosity (LOH)] in 50 sporadic ECs, and correlated the genetic findings with the immunohistochemical expression of the p16^INK4A protein and the classical clinicopathological features.Methods Gene mutations were detected by PCR-SSCP-sequencing analysis, promoter hypermethylation by methylation-specific PCR (MSP), and LOH by PCR of the STS-marker c5.1.Results In total, p16^INK4A alterations were found in 14 of 50 (28%) sporadic ECs. In six (12%) cases, two alterations occurred simultaneously. Partial p16^INK4A deletions were found in four of 50 (8%) samples. There was one missense mutation (codon 70; CCCGCC) and one frameshift mutation (1-bp deletion in exon 2). Only 2 of 47 (4.2%) tumors exhibited aberrant promoter methylation. An allelic loss was detected in 12 of 50 (24%) carcinomas with a higher incidence in advanced endometrial carcinomas than in early-stage uterine tumors. p16^INK4A alterations were generally accompanied by gene silencing, confirmed by aberrant protein immunostaining (r=-0.442; P=0.001). There was a significant difference in the frequency of p16^INK4A alterations between early (stage I; 18%) and advanced (stages II–IV; 58%) ECs (P=0.022). One case showed complete protein loss, but absence of genetic alterations.Conclusions Our data indicate that p16^INK4A inactivation plays a role in the tumorigenesis of the subset of sporadic ECs, particularly in cases exhibiting an aggressive clinical behavior. We demonstrate that p16^INK4A methylation can act efficiently and similarly to other genetic alterations as one of the two necessary hits according to the Knudson two-hit hypothesis of tumor suppressor gene inactivation.     

Coexpression of VEGF-C and Cox-2 in Human Colorectal Cancer and its Association With Lymph Node Metastasis

Purpose Several lines of experimental evidence indicated that over-expression of vascular endothelial growth factor-C and cyclooxygenase-2 genes promotes angiogenesis and lymphangiogenesis, both of which are essential for the growth and spreading of tumor cells. This study was designed to evaluate the coexpression of vascular endothelial growth factor-C and cyclooxygenase-2 in human colorectal carcinoma to determine their relationships and correlations with lymph node metastasis and prognosis. Methods Tissue samples of primary tumors and metastatic lymph nodes from 150 patients undergoing intentionally curative surgical resections for colorectal adenocarcinoma were immunohistochemically examined for vascular endothelial growth factor-C, cyclooxygenase-2, and CD34 expressions. Then, we analyzed their relationships and correlations with clinicopathologic findings and patients' survival time. Results The positivity rate of vascular endothelial growth factor-C and cyclooxygenase-2 in the primary tumor was 68 and 72.7 percent, respectively, and in the metastatic lymph nodes was 93.3 and 80 percent, respectively. A significant correlation was found between the expression scores of vascular endothelial growth factor-C and cyclooxygenase-2 (P < 0.0001), and both also were correlated to microvessels density and several clinicopathologic parameters, including primary tumor size, lymph node metastasis, lymphatic invasion, and TNM stage. Patients with vascular endothelial growth factor-C-positive and/or cyclooxygenase-2-positive tumors had a significant shorter survival time than those with negative tumors did. However, in a multivariate analysis, only cyclooxygenase-2 expression was recognized as an independent prognostic factor (P = 0.0412; relative risk ratio, 3.067; 95 percent confidence interval, 1.046–8.994). Conclusions These data show that in human colorectal carcinoma, vascular endothelial growth factor-C and cyclooxygenase-2 are coexpressed and significantly associated with lymph node metastasis and prognosis. Supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan. Presented at the meeting of the Japan Society of Clinical Oncology, Kyoto, Japan, October 27 to 29, 2004.     

Alteration of the <Emphasis Type="Italic">p14</Emphasis><Superscript><Emphasis Type="Italic">ARF</Emphasis></Superscript> gene and p53 status in human hepatocellular carcinomas

Background The INK4a/ARF locus encodes p16^INK4a and p14^ARF, both of which are crucial for two tumor suppressor pathways, retinoblastoma (RB)/p16^INK4a and p53/ARF. Inactivation of RB/p16^INK4a was frequently reported, but alterations of the p14^ARF gene in hepatocellular carcinoma (HCC) in the Japanese population have been insufficiently analyzed.Methods To determine the role of p53/ARF alteration in hepatocarcinogenesis, we examined 44 HCCs for mRNA expression, deletion, mutation, and promoter hypermethylation of the p14^ARF gene; alterations of p53 were also analyzed in the same series of HCCs.Results Homozygous deletion, spanning from exon 1 to exon 2, was found in 1 HCC mutations within exon 2 were found in 2 HCCs, but no promoter hypermethylation was detected. All 3 HCCs with p14^ARF alteration were well differentiated. Twelve of the 44 HCCs (27.2%) showed immunohistochemical evidence of p53 alteration; however, only 1 of the tumors with p53 alteration was well differentiated. TaqMan polymarase chain reaction (PCR) indicated that the expression of p14^ARF in HCCs was higher than in that in all but three of the corresponding non-tumorous tissues (P < 0.0001), and increased expression of p14^ARF seemed to be associated with poorly differentiated phenotype. Absence of p14^ARF expression was seen in only one HCC, with homozygous deletion of the p14^ARF gene.Conclusions Compared with p53 alteration, p14^ARF alteration does not occur frequently, but may play a role in a subset of Japanese HCCs in the early stage of hepatocarcinogenesis. On the other hand, overexpression of p14^ARF was frequently observed in HCC, especially in poorly differentiated tumors, probably reflecting oncogenic stimuli in these tumors.     

Predictive Histopathologic Factors for Lymph Node Metastasis in Patients With Nonpedunculated Submucosal Invasive Colorectal Carcinoma

PURPOSE Risk factors for lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma remain to be characterized. This study examines the relationship between lymph node metastasis and clinicopathologic factors in nonpedunculated submucosal invasive colorectal carcinoma.METHODS The study cohort comprised 155 patients who had undergone surgical treatment for nonpedunculated submucosal invasive colorectal carcinoma. The clinicopathologic factors investigated included gender, age, tumor location, macroscopic type, tumor size, histologic type and grade, intramucosal growth pattern, lymphatic invasion, venous invasion, degree of focal dedifferentiation at the submucosal invasive front, status of the remaining muscularis mucosa, and the depth and width of submucosal invasion.RESULTS Lymph node metastases were found in 19 patients (12.3 percent). Univariate analysis showed that lymphatic invasion, focal dedifferentiation at the submucosal invasive front, status of the remaining muscularis mucosa, and depth of submucosal invasion all had a significant influence on lymph node metastasis. Multivariate analysis showed lymphatic invasion (P = 0.014) and high-grade focal dedifferentiation at the submucosal invasive front (P = 0.049) to be independent factors predicting lymph node metastasis. No lymph node metastasis was found in tumors with a depth of submucosal invasion of <1.3 mm.CONCLUSIONS Lymphatic invasion and high-grade focal dedifferentiation at the submucosal invasive front are important predictors of lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma. Depth of submucosal invasion can be used as an identifying marker for patients who do not require subsequent surgery after endoscopic resection.Supported in part by a grant-in-aid for cancer research from the Ministry of Health and Welfare of Japan.     

MDM2 mRNA Expression in the p53 Pathway May Predict the Potential of Invasion and Liver Metastasis in Colorectal Cancer

Purpose  The p53/MDM2/p14ARF pathway is one of the major signaling cascades involved in the regulation of apoptosis. Although many tumors have been reported to show disruption of the p53/MDM2/p14ARF pathway, few studies have examined p53, MDM2, and p14ARF simultaneously in colorectal carcinoma. The present study was undertaken to clarify whether correlations exist among MDM2, p53, and p14ARF in colorectal cancer. Methods  We determined the presence of mutations in the p53 gene, MDM2 expression, and methylation status of the p14ARF in 97 primary colorectal carcinoma specimens. Associations with survival and clinicopathologic factors were investigated. Results  At least one abnormality of these three molecules was found in 82 (84 percent) tumors. We observed a significant inverse association between MDM2 expression and tumor invasion (P = 0.01). Furthermore, the presence of liver metastasis was also significantly associated with low MDM2 expression (P = 0.02). Conclusions  The results suggest that disruption of the p53/MDM2/p14ARF pathway may frequently participate in colonic carcinogenesis and that MDM2 expression status may be a factor in the prediction of potential invasion and liver metastasis of colorectal carcinomas. Reprints are not available.     

Cyclooxygenase-2 Expression as a New Marker for Patients with Colorectal Cancer

PURPOSE: Epidemiologic studies indicate that the use of nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase activity, reduce the risk of colorectal cancer. In addition, several studies demonstrate increased expression of cyclooxygenase-2 in human colorectal cancer tissues. However, the role of cyclooxygenase-2 expression in colorectal cancer has not yet been fully established. The aim of this study was to clarify the clinicopathologic significance of cyclooxygenase-2 expression in human colorectal cancer. METHODS: A total of 232 surgically resected colorectal cancer specimens were analyzed immunohistochemically with the use of a murine anti-human cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was then compared with clinicopathologic background and survival outcome. RESULTS: Cyclooxygenase-2 was expressed in the cytoplasm of the cancer cells but not in normal epithelium. Cyclooxygenase-2 expression was noted in 71.6 percent (166/232) of the cancer patients and correlated significantly with histologic type (P = 0.033), depth of invasion (P = 0.016), pathologic stage (P = 0.020), and metachronous liver metastasis (P = 0.001). Multivariate analysis for factors associated with metachronous liver metastasis showed that cyclooxygenase-2 expression was one of the independent risk factors, second only to lymph node metastasis. Patients with cyclooxygenase-2 expression showed a significantly poorer outcome compared with those without cyclooxygenase-2 expression (P = 0.002). CONCLUSION: Cyclooxygenase-2 expression in the primary lesion may be a useful marker for evaluating prognosis and liver metastasis in patients with colorectal cancer.     

Immunohistochemical localization of carcinoembryonic antigen as a predictor of lymph node status in submucosa-invasive colorectal carcinoma

PURPOSE: Submucosa-invasive colorectal carcinoma is a colorectal carcinoma extending only into the submucosal layer. To clarify the metastatic potential of submucosa-invasive colorectal carcinoma, we studied the relationship between the immunohistochemical staining pattern of carcinoembryonic antigen (CEA) and that of lymphatic invasion/ lymph node metastasis. METHODS: We investigated 49 submucosa-invasive colorectal carcinomas resected surgically or endoscopically. CEA distribution patterns of the neoplastic tissues were divided into three patterns: Pattern 1 = luminal type; Pattern 2 = apical cytoplasmic type; and Pattern 3 = diffuse cytoplasmic type. We also observed the submucosal stromal staining of CEA. RESULTS: Lymphatic invasion and lymph node metastasis were found in 48.8 percent (21/43) and 11.6 percent (5/43) of the Pattern 2/Pattern 3 cases, whereas these were seen in none (0/6) of Pattern 1 cases. Lymphatic invasion and lymph node metastasis were found in 63.3 percent (19/30) (chi-squared =21.94;P <0.001) and 16.7 percent (5/30) of the positive stromal CEA cases, whereas these were seen in 10.5 percent (2/19) and none (0/14) of the negative stromal CEA cases, respectively. CONCLUSION: Pattern 2/Pattern 3 and stromal CEA can be predictors of the lymph node metastasis with 11.6 percent and 16.7 percent risks.Read at the meeting of the Japanese Society of Gastroenterological Surgery, Tokyo, Japan, February 24 to 25, 1994.     

Aberrant Methylation of HLTF, SOCS-1, and CDH13 Genes Is Shown in Colorectal Cancers Without Lymph Node Metastasis

PURPOSE and METHODS In this study, we examined the combined methylation status of HLTF, SOCS-1, and CDH13 in 61 resected primary colorectal cancers using methylation-specific polymerase chain reaction and correlated the number of methylated genes with the clinicopathologic features of affected patients.RESULTS We found a significant difference in lymph node metastasis (P = 0.020) when we compared the number of methylated genes in colorectal cancers with lymph node metastasis to those without it.CONCLUSIONS Colorectal cancers without lymph node metastasis frequently exhibited the aberrant methylation of HLTF , SOCS-1 , and CDH13 genes.     

Curative Resection of T1 Colorectal Carcinoma: Risk of Lymph Node Metastasis and Long-Term Prognosis

PURPOSE The features of T1 colorectal adenocarcinoma and the risk determination of lymph node metastasis were reviewed. Prognostic factors were assessed to verify whether the risk of lymph node metastasis would influence the long-term prognosis.METHODS Patients undergoing curative resection of T1 colorectal adenocarcinoma at the Taipei Veterans General Hospital from December 1969 to August 2002 were retrospectively studied. Patients with synchronous colorectal cancer, distant metastasis, familiar adenomatous polyposis, or inflammatory bowel disease were excluded. The associations between lymph node metastasis and clinicopathologic variables were evaluated univariately using chi-squared test, Fisher’s exact test, or Student’s t -test, and multivariately using logistic regression. Univariate analysis by the log-rank test and multivariate analysis by Cox regression hazards model determined the factors influencing the overall survival.RESULTS A total of 159 patients were included. Sixteen patients (10.1 percent) had lymph node metastasis. The risk of lymph node metastasis included histologic grade (P = 0.005), lymphatic vessel invasion (P = 0.023), inflammation around cancer (P = 0.049), and budding at the invasive front of tumor (P = 0.022). Age (P = 0.001) and number of total sampling lymph nodes (P < 0.0001) were found to be the factors influencing the overall survival.CONCLUSIONS Variables that predict lymph node metastasis in surgically resected T1 colorectal carcinoma may not impact the long-term prognosis.Supported by a grant from the Research Foundation of Taipei Veterans General Hospital.     

Histopathologic characteristics of colorectal cancer with liver metastasis

PURPOSE: Although prognostic factors of colorectal cancer have been studied, factors associated with liver metastasis have not been fully investigated. The aim of this study was to clarify the histopathologic characteristics of colorectal cancer with liver metastasis. METHODS: We performed a retrospective histopathologic study on 335 patients who underwent resection of colorectal cancer during 15 years. Histopathologic parameters of tumors with liver metastasis were compared with those without liver metastasis. RESULTS: Forty-one patients (12 percent) had simultaneous liver metastasis. Tumors having liver metastasis, when compared with those not having liver metastasis, were characterized by high frequency of tumor size more than 6 cm (51vs. 28 percent;P<0.01), presence of serosal invasion (98vs. 66 percent;P<0.01), lymphatic invasion (34vs. 15 percent;P<0.01), venous invasion (24vs. 3 percent;P<0.01), and lymph node metastasis (85vs. 39 percent;P<0.01). Multivariate analysis showed that factors independently associated with liver metastasis were serosal invasion, venous invasion, and lymph node metastasis. Accuracy in the diagnosis of liver metastasis was highest for venous invasion (88 percent) and lowest for serosal invasion (41 percent). Among 98 patients with both serosal invasion and lymph node metastasis, tumors with and without liver metastasis were different in frequency of venous invasion (26vs. 6 percent;P<0.01) and extracolic lymph node metastasis (68vs. 47 percent;P<0.05). CONCLUSION: In colorectal cancer important factors associated with liver metastasis were serosal invasion, venous invasion, and lymph node metastasis. Significant determinants for liver metastasis from colorectal cancer were venous invasion and extracolic lymph node metastasis.Presented at the meeting of The Japanese Society for Cancer of the Colon and Rectum, Tokyo, Japan, July 4, 1997.     

CCR7和L-选择素在大肠癌组织中的表达及意义

目的探讨CC趋化因子受体7(CCR7)和黏附分子L-选择素在大肠癌组织中的表达及二者与大肠癌淋巴转移的关系。方法采用免疫组织化学方法检测63份大肠癌组织(大肠癌组)、44份癌旁正常组织(癌旁组)和31份转移灶组织(转移组)中CCR7和L-选择素的表达。结果大肠癌组、转移组CCR7、L-选择素阳性率明显高于癌旁组(P<0.01);CCR7与L-选择素表达显著相关(r=0.653,P<0.01);有淋巴结转移者明显高于无转移者,P<0.05。结论 CCR7与L-选择素在大肠癌中的表达与大肠癌的发生和淋巴转移有关,二者可能共同参与了大肠癌发生及淋巴结转移过程;检测二者表达情况有助于判断大肠癌患者的预后。     

Immunohistochemical Expression of PCNA and CD34 in Colorectal Adenomas and Carcinomas Using Specified Automated Cellular Image Analysis System: A Clinicopathologic Study

Background/Aim:

To evaluate the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) and CD34 in colorectal adenomas and carcinomas, and to correlate this expression with different clinicopathologic parameters.

Materials and Methods:

The study was retrospectively designed. A total of 86 tissue samples, including 33 paraffin blocks from patients with colorectal adenomas, 33 paraffin blocks from patients with colorectal adenocarcinomas, and a control group of 20 samples of nontumerous colonic tissue, were included in the study. From each block, 3 sections of 5 ΅m thickness were taken, 1 section was stained with hematoxylin and eosin (H and E) and the other 2 sections were stained immunohistochemically for PCNA and CD34. Scoring of the immunohistochemical staining was performed using a specified automated cellular image analysis system (Digimizer).

Results:

PCNA expression was significantly increased in a sequence of normal mucosa–adenoma–carcinoma. It was significantly higher in adenomas ≥ 1 cm and those with severe dysplasia, and it showed a significant positive correlation with grade and lymph node involvement in colorectal carcinoma. CD34 showed significantly higher expression in carcinoma than adenoma and in adenoma than in the control group. CD34 expression showed a significant correlation with adenomas carrying severe dysplasia and large-sized adenomas (≥1cm). It was significantly correlated with tumor grade, lymphovascular invasion, and lymph node involvement in colorectal carcinoma.

Conclusion:

PCNA plays an important role in colorectal neoplastic progression and can be utilized as ancillary marker for the risk of malignant transformation in colorectal adenomas as it correlates with high grade dysplasia and size. Intratumoral quantification of the mean (A and N) of CD34 in colorectal carcinoma reflects the grade of tumors and can predict lymph node involvement and lymphovascular invasion, to make a useful additional prognostic factor.     

Clinicopathologic significance of expression of cyclooxygenase-2 in human esophageal squamous cell carcinoma

BACKGROUND/AIMS: The focus of studies on cyclooxygenase-2 (COX2) have been on its ability to mediate the biological behavior of human tumors including tumorigenesis, tumor progression, apoptosis and differentiation. The aim of the current study was to elucidate a further finding on the clinicopathologic significance of immunohistochemical expression of COX2 in esophageal squamous cell carcinoma. METHODOLOGY: The immunohistochemical expression of COX2 was examined for 68 specimens of esophageal squamous cell carcinoma (ESCC) and the correlation of COX2 expression with clinicopathologic features was examined. COX2 immunoreactivity was weak in 27 (40%) and strong in 41 (60%) of the carcinomas. RESULTS: The proportion of poorly differentiated SCCs among tumors with a strong expression of COX2 (34%, 14 of 41) was significantly higher than among tumors with a weak expression of COX2 (19%, 3 of 14, p = 0.02). The depth of the tumors (p = 0.0004), lymph node metastasis (p = 0.009) and the stage of the tumors (p = 0.001) were advanced significantly more progressively in ESCCs with a strong COX2 expression. Moreover, survival was significantly reduced (p = 0.02) among patients with strong COX2 expression when compared with the COX2 weak group. CONCLUSIONS: This study showed that strong expression of COX2 was correlated with tumor progression and poor differentiation in ESCC.     

Expression of HSP90 and HIF-1α in human colorectal cancer tissue and its significance

Objective:To investigate the expression of HSP90 and HIF-1αin human colorectal cancer tissue,the influence of HSP90 and HIF-1αon human colorectal cancer biological behavior and their related factors.Methods:The expression of HSP90 and HIF-1 a protein in human colorectal cancer as well as normal tissue were detected by imnmnohistochemical method.Results:The positive expression rates of HSP90 and HIF-1αprotein in normal human colorectal tissue as well as colorectal cancer tissue were 30%vs.63.0%,15.0%vs.71.7%,respectively.There were significant difference(P=0.035 and P=0.005 respectively).The expression of HSP90 was significantly correlated with the differentiation,Dukes stages and lymph node metastasis(P0.05),while the expression of HIF-1 a was significantly correlated with the Dukes stages and lymph node metastasis(P0.05).Association analysis showed that the expression of HSF90 protein was significantly correlated with that of HIF-1αprotein(P0.01).Conclusions:The expression of HSP90 and HIF—1αprotein may be related to the development,metastasis and invasion of human colorectal cancer,and their synergistic effects may participate in the development of the colorectal carcinoma.     

¹⁸F-fluoro-2-deoxyglucose uptake on PET CT and glucose transporter 1 expression in colorectal adenocarcinoma

AIM: To evaluate the correlation between the level of ¹⁸F-fluoro-2-deoxyglucose (¹⁸F-FDG) uptake and glucose transporter 1 (GLUT1) expression in colorectal adenocarcinoma (CRA).METHODS: Forty four patients with resected CRA and preoperative ¹⁸F-FDG positron emission tomography - computed tomography data were investigated in this study. Comparison of maximum standardized uptake value (SUVmax) of the lesion was made with GLUT1 expression by immunohistochemistry and various clinicopathologic factors including tumor volume, invasion depth, gross finding, and lymph node metastasis.RESULTS: SUVmax was 14.45 ± 7.0 in negative GLUT1 expression cases, 15.51 ± 5.7 in weak GLUT1 expression cases, and 16.52 ± 6.8 in strong GLUT1 expression cases, and there was no correlation between between GLUT1 expression and SUVmax. SUVmax was significantly correlated with tumor volume (P < 0.001). However, there was no significant differences in SUVmax and GLUT1 expression among other clinicopathologic factors.CONCLUSION: GLUT1 expression does not correlates significantly with ¹⁸F-FDG uptake in CRA. ¹⁸F-FDG uptake was increased with tumor volume, which is statistically significant.