P27kip1在结直肠癌中的表达及临床意义

Objective To investigate the significance of p27 expression in colorectal carcinomas (CRCs). Methods The samples were obtained from 44 cases. P27 expression was detected by immunohistochemistry using the SABC staining method at the three sites: carcinoma tissue, pericarcinoma (1 cm away from CRC) and the incision margin (3 cm away from CRC). Results Expression of p27 was found in 56.82% (25/44) of CRCs, in 88.64% (39/44) of percarcinoma and and in 97.73% (43/44) of the mucosa at the incison margin. P27 expression in CRCs was correlated significantly with Dukes stage (P<0.05), histology grade (P<0.01) and local lymph node involvement (P<0.05), but not with age, gender, and site or size of the CRC. Conclusion The decrease of p27 expression may be involved in the malignant transformation of colorectal epithelial cells to CRC. Expression of p27 in CRC correlates with some clinicopathological characteristics and may be of prognostic significance.     

散发性结直肠癌中微卫星不稳定性及临床病理意义

目的通过微卫星位点BAT-25和BAT-26的分析,观察散发性结直肠癌原发和转移灶中微卫星不稳定性（MSI）的阳性率,并探讨其与临床病理参数的关系。方法收集73例结直肠癌原发灶和53例转移灶石蜡标本,分离基因组DNA,通过荧光标记多重PCR法扩增微卫星位点BAT-25和BAT-26;应用全自动DNA测序仪和GeneScan 3．1软件进行片段分析,观察这2个位点重复序列长度的变化。以1例己知有MSI-H的遗传性非息肉病性结直肠癌（HNPCC）病例为阳性对照。结果73例散发性结直肠癌中,MSI的阳性率为15．1％,MSI与患者的性别、肿瘤发生部位、分化程度和预后有关（P〈0．05）;53例转移患者中,转移灶的MSI阳性率（17．0％）略高于原发灶（13．2％）,差异无统计学意义（P〉0．05）,但有2例原发灶MSI阴性,转移灶MSI阳性。结论散发性大肠癌中MSI是一个常见的分子事件;MSI可作为临床判断大肠癌恶性程度、预后等的重要参考指标,根据MSI对散发性结直肠癌进行分类有重要的理论和实际意义;MSI在部分散发性大肠癌的转移中可能起一定的作用。     

CD10蛋白在结直肠癌组织中的表达及其临床意义

目的：研究CD10蛋白在结直肠癌组织中的表达及其与结直肠癌的各临床病理指标之间的关系，探讨其在结直肠癌发生、发展中的作用。方法：收集78例结直肠癌组织标本及22例癌旁正常组织样本，运用免疫组化EliVision法检测CD10蛋白的表达，并采用卡方检验分析其表达强度及分布比例与结直肠癌临床病理指标的关系。结果：CD10蛋白在结直肠癌组织和正常结肠黏膜组织中的阳性表达率分别为46.2%（36/78）和0，差异有统计学意义（P < 0.01）。结直肠癌组织中CD10蛋白表达比例与各临床病理指标均无明显相关（P > 0.05）。结直肠癌组织中CD10蛋白表达强度与患者性别、年龄、肿瘤部位、分化程度、浸润深度无明显相关（P > 0.05），而与肿瘤的临床分期、有无脉管侵犯及淋巴结转移有关（P < 0.05），中晚期结直肠癌CD10蛋白表达强度高于早期肿瘤（P=0.033），周围淋巴结转移阳性的结直肠癌CD10蛋白表达强度高于淋巴结阴性病例（P=0.023），存在脉管受侵犯的结直肠癌CD10蛋白表达强度高于无脉管受侵病例（P=0.004）。结论：CD10蛋白在结直肠癌组织中呈高表达，且表达强度与肿瘤的临床分期、有无脉管侵犯及淋巴结转移有关，可能有促进结直肠癌发展和浸润转移的作用。     

CD10蛋白在结直肠癌组织中的表达及其临床意义

目的：研究CD10蛋白在结直肠癌组织中的表达及其与结直肠癌的各临床病理指标之间的关系,探讨其在结直肠癌发生、发展中的作用。方法：收集78例结直肠癌组织标本及22例癌旁正常组织样本,运用免疫组化EliVision法检测CD10蛋白的表达,并采用卡方检验分析其表达强度及分布比例与结直肠癌临床病理指标的关系。结果：CD10蛋白在结直肠癌组织和正常结肠黏膜组织中的阳性表达率分别为46.2%（36/78）和0,差异有统计学意义（P < 0.01）。结直肠癌组织中CD10蛋白表达比例与各临床病理指标均无明显相关（P > 0.05）。结直肠癌组织中CD10蛋白表达强度与患者性别、年龄、肿瘤部位、分化程度、浸润深度无明显相关（P > 0.05）,而与肿瘤的临床分期、有无脉管侵犯及淋巴结转移有关（P < 0.05）,中晚期结直肠癌CD10蛋白表达强度高于早期肿瘤（P=0.033）,周围淋巴结转移阳性的结直肠癌CD10蛋白表达强度高于淋巴结阴性病例（P=0.023）,存在脉管受侵犯的结直肠癌CD10蛋白表达强度高于无脉管受侵病例（P=0.004）。结论：CD10蛋白在结直肠癌组织中呈高表达,且表达强度与肿瘤的临床分期、有无脉管侵犯及淋巴结转移有关,可能有促进结直肠癌发展和浸润转移的作用。     

Vascularization in primary breast carcinomas: its prognostic significance and relationship with tumor cell dissemination.

PURPOSE: The interaction between tumor cells, stroma, and endothelial cells is important for the dissemination of tumor cells. The aim of the present study is to examine vascularity in primary breast carcinomas and its prognostic significance and relationship with tumor cell dissemination. EXPERIMENTAL DESIGN: A total of 498 invasive breast carcinomas were analyzed. Representative tumor sections were stained for CD34 and CD105, and vascularity was quantified by the Chalkley method. The relationship between Chalkley counts, vascular invasion, disseminated tumor cells (DTC) in the bone marrow, other clinicopathologic variables, and clinical outcome was evaluated. RESULTS: High vascular grades determined by Chalkley counts were significantly associated with shorter distant disease-free survival and breast cancer-specific survival in all patients (P < 0.001, log-rank) and in node-negative patients not receiving adjuvant systemic therapy (P < 0.05). In multivariate analysis, both CD34 and CD105 Chalkley counts showed prognostic significance for distant disease-free survival (P = 0.014 and P = 0.026), whereas CD34 also showed prognostic significance for breast cancer-specific survival (P = 0.007). Vascular invasion and DTCs in the bone marrow showed independent prognostic significance. DTC did not discriminate survival for CD34 low Chalkley counts, whereas a very poor prognosis was observed for DTC-positive patients with high CD34 counts. In node-negative patients not receiving systemic chemotherapy, high CD34 and high CD105 counts in combination identified patients with unfavorable outcome, as opposed to all other CD34/CD105 combinations. CONCLUSIONS: Improved identification of risk groups could be obtained by adding CD34 and CD105 vascular analysis to DTC, vascular invasion, and other primary tumor factors. This may facilitate the selection of candidates for adjuvant systemic therapy.     

Neuroendocrine differentiation in follicle-cell thyroid carcinoma: correlation to prognostic factors in papillary carcinoma

The presence of NE-differentiation in the follicle-cell thyroid carcinoma has been investigated by immunohistochemical detection of chromogranin A in the neoplastic cells. It has been found that NE-differentiation was present in a significant percentage in the papillary Ca alone (46.60%) whereas all Huerthle-cell neoplasms and the large majority of follicular and undifferentiated carcinomas showed non reactivity for Chromogranin A. Moreover, we have correlated the presence of NE-differentiation to well known prognostic factors in papillary Ca. We found a statistically significant correlation between the neuroendocrine differentiation and some unfavourable factors such as old age of the patient, size of the tumor, invasion of thyroid capsule and lymphnode involvement. We suggested that NE-differentiation could be considered as an index of poor prognosis.     

Metabotropic glutamate receptor 4 expression in colorectal carcinoma and its prognostic significance.

PURPOSE: Metabotropic glutamate receptors (mGluR) play a variety of roles in both neuronal and nonneuronal cells. Recently, we reported that mGluR4 mediates 5-fluorouracil resistance in a human colon cancer cell line. In this study, we evaluated the nonneural expression of mGluR4 and clarified the existence of mGluR4 in normal colon epithelium and colorectal carcinomas. We also investigated the association of mGluR4 expression levels with various clinicopathologic parameters. EXPERIMENTAL DESIGN: mGluR4 expression was investigated in 21 normal and 312 malignant tissues from various organs using immunohistochemistry. In addition, 241 cases of colorectal carcinomas were examined and correlations between mGluR4 expression and various clinicopathologic parameters were then statistically analyzed. RESULTS: Expression of mGluR4 was identified in the normal epithelia of the upper respiratory tract, gastrointestinal tracts, breast, uterine cervix, urinary bladder, and skin, whereas it was not detected in the thyroid, lung alveoli, liver, testis, or prostate. In the corresponding malignant tissues, mGluR4 expression was frequently identified in colorectal carcinoma (68%), followed by malignant melanoma, laryngeal carcinoma, and breast carcinomas. Expression of mGluR4 was detected in 131 (54%) of 241 colorectal carcinomas and 12 (5%) cases among them showed overexpression in their cytoplasms. Loss of mGluR4 expression was negatively associated with tumor differentiation (P = 0.028), whereas overexpression of mGluR4 was positively associated with recurrence (P = 0.034) and poor disease-free survival (P = 0.017) in multivariate analyses. CONCLUSIONS: Our results suggest that mGluR4 signaling may play a role in colorectal carcinomas and that overexpression of mGluR4 is associated with poor prognosis.     

结直肠癌患者 DHRS9的表达及其临床意义

目的：探讨脱氢酶/还原酶家族成员9（DHRS9）表达对结直肠癌临床预后的意义。方法：采用免疫组织化学染色方法检测163例临床结直肠癌组织样本,并挑选58例新鲜样本,提取总蛋白和总 RNA,采用Western blot 和 qPCR 方法检测 DHRS9表达情况。结果：Western blot 和 qPCR 检测结果表明,结直肠癌组织中DHRS9蛋白和 mRNA 表达均下调,且淋巴结转移（P =0.032）、TNM 晚期（P =0.021）、疾病复发（P =0.001）和患者死亡（P =0.014）显著影响 DHRS9表达。Kaplan - Meier 分析结果显示,DHRS9表达下调预示患者无病生存期（P =0.003）和疾病特异性生存时间（P =0.021）较短。Cox 多变量分析表明,DHRS9表达下调是结直肠癌患者疾病预后不良的独立预后标志物。此外,联合采用 DHRS9表达检测和 TNM 分期对患者预后进行判断更加准确。结论：DHRS9表达下调与结直肠癌患者肿瘤发展密切相关,可以作为结直肠癌患者疾病临床预后标志物。     

复发转移性结直肠癌的外科治疗及预后分析

背景与目的:结直肠癌是常见恶性肿瘤之一,其发病率有逐渐增高的趋势.其主要的治疗方法是根治性手术,手术后的复发及转移是导致患者死亡的主要原因.目前复发性结直肠癌的再手术是提高患者生存率和生存质量的主要方法.本文探讨结直肠癌术后复发的原因、诊断和外科治疗方法.方法:回顾性分析2003-2006年35例复发与转移性结直肠癌的外科治疗及预后.结果:手术后1年内复发者9例 (26%),3年内复发者26例(74 %).本组35例复发或转移性结直肠癌均行再次手术,7例复发性直肠癌再切除4例,造瘘3例,28例复发性结肠癌中,根治性切除8例(包括5例肝转移灶切除),姑息性切除10例,盲肠或横结肠造瘘10例.总切除率为63 %(22/35),其中根治性切除率为55%(12/22),姑息性切除45%(10/22).术后随访6～36个月,2例失访,12例根治性切除组中,9例无瘤生存,1例肺转移,2例肝转移;23例姑息治疗组中,5例死亡,4例肝转移,其余14例带瘤生存.结论:结肠癌的手术治疗,应根据其生物学特点,采取规范的手术方式、彻底清除原发灶、转移的肠系膜及淋巴结,术中注意无瘤操作,术后酌情辅以化疗或放疗,定期随访,是预防结直肠癌术后复发的主要措施.而对复发和转移病例,应根据其部位、临床特征,选择以手术为主的综合治疗方案,酌情达到根治或姑息治疗的目的.     

Rb蛋白在结直肠癌中的表达及临床意义

目的 分析Rb蛋白表达与结直肠癌临床病理特征的关系。方法 应用免疫组化SABC法，检测44例结直肠癌癌中心、癌旁（距肿瘤边缘1cm)、切缘（距肿瘤边缘3cm以上）Rb蛋白表达情况，并分析Rb蛋白表达与结直肠癌临床病理特征的关系。结果 44例结直肠癌癌中心Rb蛋白表达为61.36%（27／44）,癌旁粘膜为90.91%(40/44)，切缘为97.73%（43／44）；Rb蛋白表达与年龄、性别、肿瘤部位、大小及分化程度无显著相关，而与肿瘤临床分期及淋巴结转移显著相关。结论 Rb蛋白的表达与结直肠癌的部分临床病理特征密切相关，可能是判断结直肠癌预后的一项重要指标。     

p53 in colorectal cancer: clinicopathological correlation and prognostic significance

p53 protein was detected by immunohistochemistry in 42% of 52 colorectal adenocarcinomas. Positive tumours were significantly more frequent in the distal colon, and demonstrated a higher rate of cell proliferation. No correlation was found with tumour grade, Dukes' stage, presence of DNA aneuploidy or patient survival. The role of p53 in colorectal carcinogenesis is discussed with particular reference to differences between proximal and distal large bowel cancers.     

Ezrin在散发性结直肠癌中的表达及意义

Objective： The membrane-linking protein Ezrin is highly expressed in several types of human cancers. The correlations between its immunoreactivity and histopathological data as well as patient outcome have previously been shown. However, the role played by Ezrin in the carcinogenesis, progression and metastasis of primary sporadic colorectal carcinoma （SCRC） is still under investigation. This study assessed Ezrin protein expression in a series of clinical specimens. Methods： Immunohistochemical analysis was used to characterize patterns of Ezrin expression in 132 cases of SCRC, including 74 metastatic cases and 58 non-metastatic cases and 43 adjacent normal colorectal mucosa. Results： （1） The expression rate of Ezrin in SCRC （79.5%） was significantly higher than in adjacent normal colorectal mucosa （11.6%） （P 〈 0.001）; （2） The total expression rate of Ezrin was 86.5% and 70.7% in metastatic group and non-metastatic group, respectively （P = 0.026）; the membrane expression rate of Ezrin was 31.1% and 6.9% in the two groups, respectively （P 〈 0.01）; （3） There was no relationship between the expression of Ezrin with age, gender, tumor size, location, degree of differentiation and invasive depth; （4） In the cases with followed-up data, univariate analysis demonstrated that Ezrin expression and its membrane translocation was correlated with worse patient＇s disease-free survival （DFS） （Puni 〈 0.05）. Conclusion： Ezrin was expressed in the majority of SCRC and associated with adverse prognostic factors. The increase expression and the switch of Ezrin localization from the cytoplasm to the membrane were closely correlated with metastasis in SCRC. It might be served as an important parameter for determining tumor biological behavior.     

Heterogeneity and prognostic significance of macrophages in human colonic carcinomas

Previously, we reported that high concentrations of eosinophils in human colonic carcinomas are associated with better prognoses, that sections taken 1 cm remote from (deep to) the margin of tumor (SRM) and sections contiguous to the margin (SCM) of tumor and adjacent uninvolved colon contain significantly different concentrations of eosinophils, and that concentrations of eosinophils in SCM and SRM are both useful and complementary for the prediction of prognosis. As a first step towards studying the ecology of the eosinophil in colonic carcinoma and with the goal of identifying other kinds of cells that might be useful for the prediction of prognosis, we counted cells in SCM and SRM that expressed histochemically demonstrable acid phosphatase, alpha-naphthylbutyrate esterase, and peroxidase. The tumors of patients with and without metastases at the time of resection of the primary tumor contained different (P = 0.0314) concentrations of cells with histochemically demonstrable alpha-naphthylbutyrate esterase in SCM but not in SRM. In contiguous 1- to 2-micron sections, morphologically macrophage-like cells with histochemically demonstrable acid phosphatase and cells with histochemically demonstrable alpha-naphthylbutyrate esterase were found to be present in different concentrations both in SCM (P less than 0.01) and in SRM (P less than 0.01); i.e., these phenotypic markers appear to identify different subpopulations of macrophages in tumors. In contrast to our previous study of human pulmonary alveolar macrophages, examination of sections stained sequentially for these phenotypic markers that are commonly used for the identification of macrophages in tumors revealed numerous cells in the same sections that expressed histochemically demonstrable acid phosphatase (red) but not alpha-naphthyl butyrate esterase (brown) and vice versa. Several of these markers promise to be useful and complementary for the prediction of prognosis.     

Expression and prognostic significance of angiopoietin in colorectal carcinoma

BACKGROUND AND OBJECTIVES: Growth and metastasis of malignant tumors depend on the angiogenesis. The aim of this study was to elucidate the prognostic significance of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) expression in advanced colorectal carcinoma. METHODS: Totally, 101 patients with surgically resected advanced colorectal carcinomas were enrolled. The tumor expressions of Ang-1 and Ang-2 were evaluated immunohistochemically, and their relationships with clinicopathological factors and prognosis were investigated. Tumor microvessel density (MVD) was also calculated and correlated with angiopoietin expression. RESULTS: Ang-1 and Ang-2 were detected in 26 (25.7%) and 45 (44.6%), respectively, of 101 cancerous lesions. Overexpression of Ang-1 was correlated with high MVD. Overexpression of Ang-2 was correlated with lymph node metastasis, venous invasion, preoperative carcinoembryonic antigen levels, and high MVD (P < or = 0.05). MVD was not significantly upregulated by Ang-1 expression, but was significantly upregulated by Ang-2 expression (P < or = 0.01). However, only patients with Ang-2 overexpression showed a significantly worse prognosis than those without Ang-2 overexpression. Multivariate analysis with logistic regression for 5-year survival revealed that cancerous stage and Ang-2 overexpression were independent prognostic indicators. CONCLUSIONS: The Ang-1 expression correlated with MVD. However, Ang-2 expression was a useful prognostic marker in the management of patients with advanced colorectal carcinoma.     

Colony forming ability of human breast carcinomas: lack of prognostic significance

To study whether colony growth in vitro reflects the prognosis of breast cancer patients, specimens from a total number of 138 patients with primary breast carcinomas were cultivated in the Courtenay-Mills soft agar method. The plating efficiency (PE) values were related to various clinical and histopathological parameters. No significant correlation was found between colony forming ability and menopausal status, histopathology, TNM-status or steroid hormone receptor status. The crude survival of the patients was not significantly correlated to the in vitro growth of the tumours; neither was there any difference in relapse-free survival between patients whose tumours failed to grow in vitro and those having growing tumours (PE greater than 0). A multivariate survival analysis of 115 patients with primary tumours without distant metastases revealed that the PE was not a significant independent prognostic indicator, as it gave no additional prognostic information above that of node and ER status. It is concluded that routine measurement of colony formation in vitro is not warranted in the management of breast cancer.     

Minichromosome maintenance protein 7 in colorectal cancer: implication of prognostic significance

Minichromosome maintenance (MCM) proteins are essential components for DNA replication, and also prognostic markers for various human tumors. MCM-positive but Ki67-negative cells (e.g. primary oocytes) are thought to be licensed non-proliferating populations, and are significantly correlated with the clinicopathological profiles of some human tumors. In the present study, we evaluated the expression levels of MCM7, MCM2 and Ki67 in colorectal cancer to clarify their pathobiological significance. We carried out Western blot analyses of 5 human colorectal cancer cell lines and performed immunohistochemistry on 202 surgically removed colorectal cancers of Dukes' B and C stages. Double-labeling immunofluorescence was also carried out on the cancer specimens to identify MCM-positive but Ki67-negative tumor cells. MCM proteins were detected in all the 5 cell lines examined. MCM7 and MCM2 were coexpressed in almost the same populations of tumor cells, whereas MCM7-negative but Ki67-positive tumor cells were absent in the double-labeled specimens, except for mitotic cells. The mean positive tumor labeling indexes (LIs) for MCM7, MCM2 and Ki67 were 58.1, 57.1 and 40.6%, respectively. The mean LI for MCM7-positive but Ki67-negative tumor cells was 17.6%, and significantly correlated with the N status (P=0.01), distant metastasis (P=0.01) and UICC stage (P=0.02). The high LI of >58.1% for MCM7 were independent prognostic factors in multivariate Cox regression analysis (relative risk = 2.12; P=0.02). Our results indicate that MCM7 expression is an independent prognostic factor for human colorectal cancer, and MCM7-positive but Ki67-negative tumor cells are correlated with tumor metastases.     

Gastric and intestinal phenotypic marker expression in gastric carcinomas and its prognostic significance: immunohistochemical analysis of 136 lesions

OBJECTIVE: It is well known that both gastric and intestinal phenotypic cell markers are expressed in gastric carcinomas, irrespective of their histologic type. However, the clinicopathologic significance of these expressions has not yet been clarified. METHODS: We analyzed the correlations among gastric and intestinal phenotypic marker expression patterns of the tumor, clinicopathologic findings and the patient's outcome in 136 advanced gastric carcinomas. RESULTS: Phenotypic marker expression was immunohistochemically evaluated using the monoclonal antibodies 45M1 (anti-human gastric mucin; HGM), CLH5 (anti-MUC6), Ccp58 (anti-MUC2) and 56C6 (anti-CD10). All tumors were classified as gastric (G), gastric and intestinal mixed (GI), intestinal (I) or unclassified (UC) phenotype. Of the 136 gastric carcinomas, 50 (36.8%), 56 (41.2%), 21 (15.4%) and 9 (6.6%) were classified as G, GI, I and UC phenotype, respectively. The G-phenotype tumors were associated with a higher rate of undifferentiated-type and infiltrative histology as compared with the I-phenotype tumors (p < 0.05 and p < 0.001, respectively). Furthermore, both univariate and multivariate analysis of survival revealed the G-phenotype tumor to be associated with a significantly poorer outcome than the I-phenotype tumor (p < 0.05). CONCLUSION: Our present results indicate that the gastric and intestinal phenotypic marker expression pattern of tumors, determined by the combination of HGM, MUC6, MUC2 and CD10 expression, is prognostically useful for patients with gastric carcinoma.     

Growth differentiation factor 15: a prognostic marker for recurrence in colorectal cancer

Background:

Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta superfamily and has been associated with activation of the p53 pathway in human cancer. The aim of this study was to assess the prognostic value of GDF15 in patients with colorectal cancer (CRC).

Methods:

Immunohistochemistry and tissue microarrays were used to analyse GDF15 protein expression in 320 patients with CRC. In a subgroup of 60 patients, the level of GDF15 protein in plasma was also measured using a solid-phase proximity ligation assay.

Results:

Patients with CRC with moderate to high intensity of GDF15 immunostaining had a higher recurrence rate compared with patients with no or low intensity in all stages (stages I–III) (HR, 3.9; 95% CI, 1.16–13.15) and in stage III (HR, 10.32; 95% CI, 1.15–92.51). Patients with high plasma levels of GDF15 had statistically shorter time to recurrence (P=0.041) and reduced overall survival (P=0.002).

Conclusion:

Growth differentiation factor 15 serves as a negative prognostic marker in CRC. High expression of GDF15 in tumour tissue and high plasma levels correlate with an increased risk of recurrence and reduced overall survival.