IMP3 expression in biopsy specimens of colorectal cancer predicts lymph node metastasis and TNM stage

IMP3 is associated with lymph node metastasis and TNM stage and is a good independent prognostic biomarker for colorectal cancer (CRC). However, the expression status and clinical implication of IMP3 in biopsy specimens have not yet been studied. We aim to address whether the presence of IMP3 expression in preoperative biopsies of CRC could predict lymph node metastasis and TNM stage. In this study, we examined IMP3 expression in paired biopsy and resection specimens of 71 CRC and analyzed the correlation of IMP3 expression with clinicopathological parameters. In the biopsy specimens, IMP3 positive expression was observed in 56 of 71 cases (78.9%) whereas negative expression was observed in 15 of 71 cases (21.1%). In the resection specimens, IMP3 positive expression was detected in 83.1% cases (59/71) whereas negative expression was detected in 16.9% cases (12/71). The absolute concordance rate between biopsy and resection specimens was 90.1% (64/71). The Spearman correlation test documented the existence of a strong linear correlation between the percentage of IMP3-positive cells in the biopsy and resection specimen (r = 0.629; P < 0.001). IMP3 expression in resection specimens was significantly related to histological grade (P = 0.043), T classification (P = 0.035), lymph node metastasis (P = 0.023), TNM stage (P = 0.007), tumor border (P = 0.049) and tumor budding (P = 0.012). IMP3 expression in biopsy specimens was significantly related to lymph node metastasis (P = 0.004), TNM stage (P = 0.005) and tumor budding (P = 0.001). In conclusion, IMP3 expression in biopsy specimens could be used to predict lymph node metastasis and TNM stage in CRC patients.     

Mixed Carcinoma as an Independent Prognostic Factor in Submucosal Invasive Gastric Carcinoma

Mixed carcinoma shows a mixture of glandular and signet ring/poorly cohesive cellular histological components and the prognostic significance of each component is not fully understood. This study aimed to investigate the significance of the poorly cohesive cellular histological component as a risk factor for lymph node metastasis and to examine the diagnostic reliability of endoscopic biopsy. Clinicopathologic characteristics of 202 patients who underwent submucosal invasive gastric carcinoma resection with lymph node dissection in 2005–2012 were reviewed. Mixed carcinoma accounted for 27.2% (56/202) of cases. The overall prevalence of lymph node metastasis was 17.3% (35/202). Lymphatic invasion (P < 0.001), family history of carcinoma (P = 0.025), tumor size (P = 0.004), Lauren classification (P = 0.042), and presence of any poorly cohesive cellular histological component (P = 0.021) positively correlated with the lymph node metastasis rate on univariate analysis. Multivariate analyses revealed lymphatic invasion, family history of any carcinoma, and the presence of any poorly cohesive cellular histological component to be significant and independent factors related to lymph node metastasis. Review of preoperative biopsy slides showed that preoperative biopsy demonstrated a sensitivity of 63.6% and a specificity of 100% in detecting the presence of the poorly cohesive cellular histological component, compared with gastrectomy specimens. The presence of any poorly cohesive cellular histological component was an independent risk factor associated with lymph node metastasis in submucosal invasive gastric carcinoma. Endoscopic biopsy had limited value in predicting the presence and proportion of the poorly cohesive cellular histologic component due to the heterogeneity of mixed carcinoma.     

Expression of p53 and NDP-K/nm23 in gastric carcinomas--association with metastasis and clinicopathologic parameters.

To evaluate the role of p53 and NDP-K/nm23(nm23) protein as a prognostic factor and their relation to metastasis of cancer, we studied metastatic and nonmetastatic gastric carcinoma specimens by immunohistochemical staining. Among the 101 specimens examined, 37(36.6%) showed positivity in staining for p53 protein and 64(63.4%) showed no detectable p53 protein in tumor cells. p53 overexpression was correlated with depth of invasion, lymphatic invasion, lymph node metastasis and distant metastasis. Out of 101 specimens, 35 cases had no staining for nm23. 62 cases(61.4%) exhibited a cytoplasmic staining on most cells and 42 cases (41.6%) had nuclear staining. In 16 of 101 cases(15.8%), a mild to moderate membranous staining was observed in some cells. Cytoplasmic nm23 expression was negatively correlated with lymph node metastasis(P < 0.01) and distant metastasis(P < 0.01). The nuclear nm23 expression showed negative correlation with depth of invasion(P < 0.01), lymphatic invasion(P < 0.01), lymph node metastasis(P < 0.01), and distant metastasis(P < 0.04). The membranous nm23 expression revealed negative correlation with lymphatic invasion(P < 0.02), lymph node metastasis(P < 0.01) and distant metastasis(P < 0.02).     

Analysis of pathological risk factors for lymph node metastasis of submucosal invasive colon cancer.

There are currently no universally accepted indications and criteria for additional surgical resection of the colorectum after endoscopic resection of the submucosal invasive cancer. The purpose of the present study is to establish accurate indications and criteria for additional surgical resection of the colorectum, based on the prediction of lymph node metastasis, after endoscopic resection of the submucosal invasive cancer. We investigated 140 submucosal invasive colorectal cancers and analyzed the pathologic factors of lymph node metastasis. The tumors were evaluated for pathologic factors in the invasive area of the submucosal carcinoma and were compared between the cases with lymph node metastasis and those without lymph node metastasis. Lymph node metastasis was observed in 13 cases (9%). Univariate logistic regression analysis showed that the depth of invasion, cribriform-type structural atypia, absence of lymphoid infiltration, lymphatic permeation, and venous permeation were statistically significant as risk factors for lymph node metastasis. Multivariate logistic regression analysis showed that the important risk factors included, in decreasing order, lymphatic permeation, absence of lymphoid infiltration, cribriform-type structural atypia, venous permeation, and depth of invasion. Submucosal invasion of 2 mm or more, and/or, depth of lymphatic permeation of 2 mm or more are risk factors for lymph node metastasis. The pathologic criteria based on our results for additional colectomy enables greater accuracy selection of patients who will undergo further surgical treatment after endoscopic resection.     

中性粒细胞与淋巴细胞比值联合检测纤维蛋白原对结直肠癌预后的判断价值

目的: 探讨中性粒细胞与淋巴细胞比值(NLR)和纤维蛋白原(Fibrinogen,FIB)联合形成指标FIB-NLR 在结直肠癌预后中的临床意义。方法:回顾性分析我院2010 年6 月至2011 年6 月接受手术治疗的250 例结直肠癌患者的临床资料,分别分析NLR 和FIB 与结直肠癌的病理特征的关系,将NLR 与FIB 进行联合形成一个指标(FIB-NLR)。将250 名结直肠癌患者分为3 组,患者NLR逸2.95 及FIB逸348 mg/ dl 定为FIB-NLR 2 分组,NLR逸2.95 及FIB<348 mg/ dl 或者NLR<2.95 及 FIB逸348 mg/ dl 定为1 分组,NLR<2.95 及FIB<348 mg/ dl 为0 分组,并分析3 组患者在结直肠癌的浸润深度、分期、淋巴结转移、神经浸润、远处转移、组织学分级中是否具有差异性。并将3 组患者按生存时间做生存分析,并对3 组患者的生存率进行比较。结果:中晚期及有淋巴结转移结直肠癌患者NLR 值明显高于分期较早及无淋巴结转移患者的NLR,差异具有统计学意义(P<0.001),肿瘤浸润深度较深、有神经浸润、有远处转移的患者其NLR 值明显高于浸润深度较浅、无神经浸润、无远处转移患者的NLR 值,差异具有统计学意义(P =0.006、P =0.002、P =0.007)。中晚期、有淋巴结转移、有远处转移的结直肠癌患者其FIB 值明显高于早期及无淋巴结转移、无远处转移的结直肠癌患者的FIB 值,差异具有统计学意义(P<0.001),浸润深度越深及有神经浸润的结直肠癌患者FIB 值明显高于浸润深度浅及无神经浸润患者的FIB 值,差异具有统计学意义(P =0.015、P=0.012)。NLR 与FIB 均在肿瘤的组织学分级、年龄大小、性别肿瘤部位无明显关联(P>0.05)。结直肠癌的临床分期越晚、浸润深度越深、有淋巴结转移、有远处转移、有神经浸润的患者其FIB-NLR 评分较早期、浸润深度浅、无淋巴结转移及无远处转移、无神经浸润患者高,差 异具有统计学意义(P<0.001)。生存分析发现,评分越高组其5 年生存率越低,差异具有统计学意义(P =0.001)。结论:FIB-NLR 可能是一个潜在的判断结直肠癌进展及预后的有效指标。     

Depressed-type of early colon cancer with extensive lymph node metastasis

Early colorectal cancer (ECC) is defined as invasive tumor limited to the colonic and rectal mucosa or submucosa, regardless of the presence or absence of lymph node metastasis. The incidence of lymph node metastasis in ECC ranges from 0 to 15.4%, and risk factors include depth of submucosal invasion, growth patterns (polypoid or non-polypoid), histologic subclassification, and lymphatic invasion. Of non-polypoid growth patterns, the depressed types of colorectal cancer have higher malignant potential than polypoid types, even for small sizes. Unfortunately, this type is also difficult to detect on colonoscopic examination. In this report, we describe a case of depressed type ECC with extensive lymph node metastasis without regional lymph node involvement.     

Role of the integrin-binding protein osteopontin in lymphatic metastasis of breast cancer

Although a primary route of breast cancer metastasis is believed to be via lymphatics, the molecular factors involved are poorly understood. We hypothesized that one such factor may be the integrin-binding protein osteopontin (OPN), and we investigated this clinically and experimentally. In breast cancer patients undergoing sentinel lymph node biopsy, OPN levels were significantly higher in lymph node metastases than in the primary tumor (P < 0.001). To test the functional contribution of OPN to lymphatic metastasis and to determine whether the RGD (Arg-Gly-Asp) integrin-binding sequence of OPN is important for this process, we transfected wild-type OPN or mutant OPN (lacking the RGD sequence) into MDA-MB-468 human breast cancer cells. In vitro, cells overexpressing OPN demonstrated increased anchorage-independent growth in soft agar (P = 0.001) and increased RGD-dependent adhesion (P = 0.045). Following mammary fat pad injection of nude mice, cells overexpressing OPN showed increased lymphovascular invasion, lymph node metastases, and lung micrometastases at earlier time points (P = 0.024). Loss of the RGD region partially abrogated this effect in the lymphatics (P = 0.038). These novel findings indicate that OPN is a key molecular player involved in lymphatic metastasis of breast cancer, potentially by affecting RGD-mediated adhesive interactions and by enhancing the establishment/persistence of tumor cells in the lymphatics.     

结直肠癌淋巴管生成的特点及其临床病理意义

目的探讨结直肠癌中淋巴管的分布特点、增殖状态及其与转移和预后的关系。方法采用淋巴管特异标记podoplanin对96例结直肠癌及其相应正常组织进行免疫组织化学染色检测微淋巴管密度,以CD34标记血管检测微血管密度作为对比,并分别与Ki-67进行双标免疫组织化学染色检测淋巴管和血管增殖活性,结合结直肠癌临床病理参数和预后分析。结果结直肠癌中心及浅表部淋巴管多为闭锁的条索状,边缘区淋巴管多呈管样扩张状。结直肠癌边缘区淋巴管密度(51.2±25.5)及较正常结直肠组织(29.4±9.0)和肿瘤其他区域显著性增高(P<0.01),并且其淋巴管内皮Ki67指数(0.23±0.17)也较其他区域显著性增高(P<0.05)。结直肠癌边缘区微淋巴管密度与淋巴管受累、淋巴结转移、远处器官转移及预后密切相关(P<0.01或P<0.05)。结论结直肠癌组织中存在新生淋巴管,且主要分布于肿瘤边缘区,癌周围淋巴管密度增加与癌细胞转移相关,结直肠癌边缘区微淋巴管密度测定对评估其淋巴结转移和预后判断可能具有意义。     

Pathologic prognostic factors in esophageal squamous cell carcinoma: a follow-up study of 74 patients with or without preoperative chemoradiation therapy.

One of the primary goals of pathologic examination of esophageal squamous cell carcinoma resection specimens is to provide information regarding morphologic features which can help prognosticate and guide management of affected patients. The purpose of this study was to determine the prognostic utility of a variety of histopathologic prognostic factors in patients with esophageal squamous cell carcinoma with and without preoperative chemotherapy and radiotherapy (chemrad). Multiple clinical and histologic features such as peri-tumoral lymphocytic infiltrate, Crohn's-like lymphoid reaction, degree of residual tumor, mitosis per 1000 cells, tumor differentiation, lymphatic/vascular invasion, perineural invasion, desmoplastic reaction, and tumor growth pattern were evaluated in patients with (53) and without (21) preoperative chemrad and correlated with survival (mean follow-up, 25 mo). Data were analyzed for the entire cohort and for each separate treatment group by univariate and multivariate analysis. Patients who received chemrad showed no significant survival benefit (hazard ratio = 2.5, P = .10). In the whole cohort of patients, higher pathologic stage (P = .04), poor tumor differentiation (P = .003), increased mitotic count (P = .005), perineural invasion (P = .01), lymphatic/vascular invasion (P = .002), tumor size (P = .05), and absence of a Crohn's-like lymphoid reaction (P = .05) were significantly associated with poor survival by univariate analysis. In multivariate analysis, poor tumor differentiation (P = .005), high mitotic count (P = .01), and vascular invasion (P = .03) were important prognostic features, independent of pathologic stage, for the entire cohort. In the chemrad group only, tumor size (in patients with macroscopic residual tumor) (P = .05), lymph node metastasis (P = .03), mitotic count (P = .01), and lymphatic/vascular invasion (P = .02) were significant prognostic indicators by univariate analysis. Upon multivariate analysis, only lymphatic/vascular invasion (P = .02) and mitotic rate (P = .01) were independent predictors of survival. In the nonchemrad group, only tumor differentiation was significant by both univariate (P = .008) and multivariate analysis (P = .03). The differences in pathologic prognostic factors between chemrad and nonchemrad treated cases suggests that chemrad has a significant effect on the biologic properties of these tumors.     

Inducible nitric oxide synthase expression correlates with angiogenesis, lymphangiogenesis, and poor prognosis in gastric cancer patients

Increased nitric oxide synthase expression plays a key role in tumor progression. To examine inducible nitric oxide synthase expression and its correlation with clinical variables, such as tumor progression, angiogenesis, lymphangiogenesis, and prognosis in gastric cancer, we studied inducible nitric oxide synthase expression in gastric cancer samples from 211 patients with 5-year follow-up. CD105 and D2-40 were adopted as biomarkers for tumor angiogenesis and lymphangiogenesis, respectively. Inducible nitric oxide synthase staining was mainly found in the cytoplasm of gastric cancer tumor cells. Positive inducible nitric oxide synthase immunoreactivity was seen in 54.03% of gastric cancer specimens, which was correlated with lymph node metastasis, vascular invasion, distant metastasis, and TNM stage. Compared with inducible nitric oxide synthase negative patients, inducible nitric oxide synthase-positive patients had significantly shorter survival times and higher microvessel density and lymphatic vessel density. Intratumor and peritumor blood microvessel density and lymphatic vessel density correlated with inducible nitric oxide synthase expression (Spearman ρ test, P < .05). We conclude that inducible nitric oxide synthase expression correlates with lymph node metastasis, vascular invasion, distant metastasis, TNM stage, and poor survival rate in gastric cancer. We propose that synthesized inducible nitric oxide synthase increases angiogenesis, and lymphangiogenesis thus promotes tumor progression. Inducible nitric oxide synthase expression may be a good biomarker for poor prognosis in gastric cancer.     

Loss of membranous Ep-CAM in budding colorectal carcinoma cells.

Tumor budding is a histological feature that reflects loss of adhesion of tumor cells and is associated with locoregional metastasis of colorectal carcinoma. Although nuclear localization of beta-catenin is associated with tumor budding, the molecular mechanism remains largely elusive. In this study, we hypothesize that the epithelial cell adhesion molecule (Ep-CAM) is involved in tumor budding. In order to address this question, we performed immunohistochemistry on Ep-CAM using three different antibodies (monoclonal antibodies Ber-ep4 and 311-1K1 and a polyclonal antibody) and a double staining on beta-catenin and Ep-CAM. In addition, Ep-CAM mRNA was monitored with mRNA in situ hybridization. Subsequently, we determined the effect of Ep-CAM staining patterns on tumor spread in rectal cancer. In contrast to the tumor mass, budding cells of colorectal carcinoma displayed lack of membranous but highly increased cytoplasmic Ep-CAM staining and nuclear translocation of beta-catenin. mRNA in situ hybridization suggested no differences in Ep-CAM expression between the invasive front and the tumor mass. Importantly, reduced Ep-CAM staining at the invasive margin of rectal tumor specimens (n=133) correlated significantly with tumor budding, tumor grade and an increased risk of local recurrence (P=0.001, P=0.04 and P=0.03, respectively). These data demonstrate abnormal processing of Ep-CAM at the invasive margin of colorectal carcinomas. Our observations indicate that loss of membranous Ep-CAM is associated with nuclear beta-catenin localization and suggest that this contributes to reduced cell-cell adhesions, increased migratory potential and tumor budding.     

Angiogenic and lymphangiogenic microvessel density in breast carcinoma: correlation with clinicopathologic parameters and VEGF-family gene expression.

Angiogenesis and lymphangiogenesis are essential for breast cancer progression and are regulated by vascular endothelial growth factors (VEGF). To determine clinical and molecular correlates of these processes, we measured blood and lymphatic vascular microvessel density in 29 invasive carcinomas (22 ductal, six lobular, one papillary), using the vascular marker CD31 and the novel lymphatic marker D2-40. Microvessel density was assessed microscopically and by image cytometry, and was compared with tumor histology, grade, stage, lymph node metastasis, hormone receptors, HER2/neu status, and expression of VEGF, VEGF-C and VEGF-D by immunohistochemistry or quantitative RT-PCR. Strong correlation was observed between visual and image cytometric microvessel density using D2-40 but not CD31 (P=0.016 and 0.1521, respectively). Image cytometric CD31 microvessel density correlated with tumor size, grade, stage and lymph node metastasis (P=0.0001, 0.0107, 0.0035 and 0.0395, respectively). D2-40 microvessel density correlated with tumor stage (P=0.0123 by image cytometry) and lymph node metastasis (P=0.0558 by microscopy). Immunohistochemical VEGF signal in peritumoral blood vessels correlated with image cytometric CD31 and D2-40 microvessel density (P=0.022 and 0.0012, respectively), consistent with the role of VEGF in blood and lymphatic vascular growth. Intratumoral VEGF-C and VEGF-D expression by quantitative RT-PCR correlated with D2-40 (P=0.0291 by image cytometry) but not with CD31 microvessel density, which could suggest a selective role of VEGF-C and VEGF-D in lymphangiogenesis. CD31 and D2-40 microvessel density correlated significantly with several prognostic factors, including lymph node metastasis. Thus, measurements of angiogenesis and lymphangiogenesis may have utility for breast cancer pathology, particularly for estimation of metastatic risk.     

Codon 201 Mutation of DCC Gene and Tumor Biologic Behavior in Human Colorectal Carcinoma

Objective To explore the relationship between a point mutation of codon 201 in deleted in colorectal carcinoma ( DCC) gene and the biological behavior of colorectal carcinoma. Methods Tumor tissues and matched adjacent normal colon mucosa collected in 35 patients during surgical resection for colorectal carcinoma were analyzed. Forty normal colon mucosa tissues obtained by biopsy from patients who had neither colorectal tumor nor a family history of colorectal cancer during colonscop ic examination were used as control. Codon 201 mutatian was detected with allele-specific PCR and a restriction enzyme digestion method. The tumors were reviewed as clinical data, tumor location, histology,metastasis, and pathological staging (Dukes classification). Results The frequency of mutation at codon 201 in tumor tissue and corresponding adjacent normal mucosa was 71.4 % and 60 %, respectively, and either of the rates was significantly higher than that of normal control(32.5 % ). The point mutation rate in tumor tissues did not differ from that in the corresponding normal adjacent tissues. Statistic analysis showed that the mutation rate had no relationship to the sex, age of the patients, the histological pattern , differentiation, and invasion depth of the tumors. However, 93. 8 % of the mutation rate in colorectal cancer with lymph node invasion and/or distant metastasis is significantly higher than 52. 6 % of mutant rate in colorectal cancer uithout lymph nodes invasion or metastasis ( P <0. 05). Conclusion The point mutation at codon 201 of DCC gene is an early genetic event in colorectal cancer, and play some role in invasion and metastasis of colorectal carcinoma. It may serve as a useful genetic marker for identifying higher risk patients with colorectal carcinoma.     

VEGF-C表达与胰腺癌淋巴结转移及预后的关系

目的 观察血管内皮生长因子(VEGF)-C在胰腺癌组织内的表达情况,分析VEGF-C的表达与胰腺癌淋巴结转移和预后之间的关系。方法 取胰腺癌病例52例,其中,伴淋巴结转移组36例,无淋巴结转移组16例。应用免疫组化法和Western blot技术观察VEGF-C在胰腺癌组织内的表达。以D2-40作为淋巴管内皮特异性标记物,观察胰腺癌组织内淋巴管生成的情况。采用Kaplan-Meier法绘制生存曲线判断VEGF-C的表达对胰腺癌预后的影响。结果 Western blot和免疫组化法检测结果表明,VEGF-C主要表达于胰腺癌细胞浆内,淋巴结转移组阳性表达量明显高于无淋巴结转移组(p<0.05)。D2-40表达于胰腺癌组织内淋巴管内皮细胞,VEGF-C阳性组淋巴管数密度明显高于VEGF-C阴性组(p<0.05),表明VEGF-C的表达与胰腺癌淋巴管生成密切相关。Kaplan-Meier生存分析表明VEGF-C表达阴性患者的生存率均高于VEGF-C表达阳性患者,VEGF-C的表达影响患者的预后。结论 VEGF-C在胰腺癌的淋巴管生成和淋巴结转移过程中发挥重要作用,VEGF-C的表达是影响胰腺癌患者预后的主要因素之一。     

Up-regulated biglycan expression correlates with the malignancy in human colorectal cancers

Biglycan, an extracellular matrix protein, has been implicated in the oncogenesis and cancer development in various types of human cancer. The clinical significance of biglycan in colorectal cancer, however, remains unclear. In the present study, biglycan mRNA expression was analyzed in 110 samples (primary colorectal tumor and matched adjacent normal tissue) derived from 55 patients with colorectal cancer using quantitative real-time RT-PCR. The correlations between biglycan up-regulation and the clinicopathological data were also evaluated. We found that the up-regulation of biglycan occurred in 61.8% (34/55) of colorectal cancer tissues, and biglycan expression in colorectal cancer tissues was markedly higher than that in corresponding normal tissues (P = 0.0264). Moreover, statistical analysis displayed a significant correlation in biglycan up-regulation with poor tumor differentiation (P = 0.009), lymph node metastasis (P = 0.041), and distant metastasis (P = 0.036). However, there was no significant correlation between biglycan up-regulation and other clinicopathological factors (all P > 0.05). In conclusion, biglycan may be a potential marker for the malignancy of colorectal cancer.     

VEGF-C在卵巢癌局部淋巴结内淋巴管生成中的作用

目的观察血管内皮生长因子-C(VEGF-C)在卵巢癌组织内的表达,分析其与卵巢癌局部淋巴结内淋巴管生成之间的关系。方法取卵巢癌64例,其中,有淋巴结转移40例,无淋巴结转移24例。应用免疫组化法和Western blot技术观察VEGF-C在卵巢癌组织内的表达。以D2-40作为淋巴管内皮特异性标记物,检测卵巢癌局部淋巴结内淋巴管生成情况。结果 VEGF-C主要表达于卵巢癌细胞浆和胞膜以及癌组织周围浸润的炎性细胞,在有淋巴结转移组的表达率明显高于其在无淋巴结转移组的表达率。Western blot检测结果表明,VEGF-C蛋白在有淋巴结转移的卵巢癌组织中的表达量高于其在无淋巴结转移的卵巢癌组织内的表达量。D2-40表达于卵巢癌局部淋巴结内的淋巴管内皮细胞,在有转移的淋巴结内可见大量新生的淋巴管,淋巴管腔内存在入侵的肿瘤细胞,在无转移的淋巴结内观察到新生的淋巴管。在无淋巴结转移组病例中,卵巢癌组织VEGF-C阳性者局部淋巴结内淋巴管密度明显高于VEGF-C阴性者淋巴结内的淋巴管密度。结论 VEGF-C的表达与卵巢癌淋巴结转移密切相关,卵巢癌在发生局部淋巴结转移之前存在淋巴结内淋巴管生成的现象,卵巢癌组织内VEGF-C的表达在卵巢癌局部淋巴结内的淋巴管生成中可能发挥重要作用。     

Histopathological predictors of regional lymph node metastasis at the invasive front in early colorectal cancer

Akishima‐Fukasawa Y, Ishikawa Y, Akasaka Y, Uzuki M, Inomata N, Yokoo T, Ishii R, Shimokawa R, Mukai K, Kiguchi H, Suzuki K, Fujiwara M, Ogata K, Niino H, Sugiura H, Ichinose A, Kuroda Y, Kuroda D & Ishii T
(2011) Histopathology 59 , 470–481 Histopathological predictors of regional lymph node metastasis at the invasive front in early colorectal cancer Aims: In early colorectal cancer (ECC), prediction of lymph node (LN) metastasis is vital for the decision of additional surgical treatment after endoscopic mucosal/submucosal resection. The aim of this study was to determine the relationship between LN metastasis and comprehensive histopathological findings including the cancer microenvironment in ECC. Methods and results: Using 111 ECC cases, including 36 cases with LN metastasis, histopathological observations and immunohistochemistry for lymphatic vessel endothelial hyaluronan receptor‐1 (LYVE‐1), von Willebrand factor, matrix metalloproteinase‐7 (MMP‐7), CXC chemokine ligand‐12 (CXCL12) and angiopoietin‐like‐4 (ANGPTL4) were conducted. Relationships between LN metastasis and growth pattern, status of muscularis mucosae, depth of cancer invasion, overall histopathological type, histopathological type at the invasive front, tumour budding, neutrophil infiltration in cancer cells (NIC), fibrotic cancer‐stroma type, Crohn’s‐like lymphoid reaction, microscopic abscess formation and lymphatic invasion were determined. In addition, the expression of MMP‐7, CXCL12 and ANGPTL4 in cancer cells at the invasive front were also considered in the context of LN metastasis. By multivariate analysis, lymphatic invasion, NIC and MMP‐7 expression at the invasive front were independent predictors of LN metastasis. Conclusions: LN metastasis is regulated not only by the characteristics of cancer cells but also by microenvironmental factors of lymphatics and neutrophils, especially at the invasive front.     

Clinicopathological significance of vascular endothelial growth factor-C in breast carcinoma with long-term follow-up.

Expression of angiogenic and lymphangiogenic factors by tumors may influence the route of metastatic spread. The angiogenic factor vascular growth factor-C (VEGF-C) is implicated in the development of lymphatic vessels and promotion of lymphatic metastasis. The purpose of this study was to determine whether VEGF-C correlates with lymph node metastasis or prognosis. We assessed VEGF-C expression using immunohistochemistry in 123 invasive breast carcinomas with long-term follow-up. The relationship between VEGF-C expression and lymph node status and other established clinicopathological parameters was assessed. Whether VEGF-C expression plays a prognostic role in breast cancer was also investigated. VEGF-C expression was identified in 103 cases (83.7%). Positive VEGF-C was significantly correlated with lymph node metastasis (P = 0.0131). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that positive VEGF-C was associated with both disease-free survival (P = 0.0165) and overall survival (P = 0.0175). On the basis of our findings, VEGF-C plays a crucial role in lymph node metastasis and may be a significant prognostic factor for long-term survival in breast cancer.