Complex karyotype in a case of cutaneous lymphangiosarcoma associated with chronic lymphedema of the lower limb

Lymphangiosarcoma is a rare malignant neoplasm of endothelial cells. The term is used to describe an angiosarcoma associated with chronic lymphedema. The skin of the head and neck region is the most common site of origin. Rather few cytogenetic studies on lymphangiosarcoma are reported in the literature. We here describe a case of an 87-year-old woman, with a history of recurring lymphangitis and with an ulcerated nodular lesion of the leg. The histological diagnosis was a malignant neoplasm of vascular origin, with the morphological and immunohistochemical features of a lymphangiosarcoma. A series of antibodies (CD31, CD34, vimentin, podoplanin and HHV-8), conventional and molecular cytogenetic and Spectral Karyotyping (SKY-FISH) analyses were used to study this case.The immunohistochemical evaluation revealed that the neoplasm was positive for vimentin, CD31, CD34 and podoplanin and negative for HHV-8. The proliferation rate (Ki-67) was about 70%. Karyotype was defined using conventional cytogenetic and SKY-FISH. In addition, high-level of amplification was observed with MYC split signal probe.The morphological and immunohistochemical evaluations supported the diagnosis of lymphangiosarcoma. Moreover, the cytogenetic and molecular findings contributed towards accurately defining the karyotypic aberrations of this rare sarcoma.     

15-脂氧合酶-1 mRNA、Podoplanin在食管鳞癌中的表达及临床意义

目的 探讨15-脂氧合酶-1(15-LOX-1)和Podoplanin在食管鳞癌(ESCC)中的表达及其与肿瘤淋巴结转移的关系.方法 RT-PCR法测定45例ESCC患者癌组织和相邻癌旁正常组织中15-LOX-1 mRNA的表达,免疫组化法检测Podoplanin的表达,计数淋巴管密度(LVD).结果 15-LOX-1 mRNA在45例ESCC的表达率为28.9%(13/45),明显低于相应癌旁正常组织73.3%(33/45),P<0.05.Podoplanin特异表达于淋巴管内皮,多位于癌巢周围间质中.40例ESCC中,淋巴结转移组LVD均值高于无淋巴结转移组(P=0.019).15-LOX-1 mRNA和LVD均值与肿瘤分化程度、淋巴结转移有关.结论 15-LOX-1表达下调与食管鳞癌分化程度和病期进展有关.肿瘤内部存在的新生淋巴管可能参与了肿瘤淋巴道转移.Podoplanin是较特异的淋巴内皮标志物,通过检测Podoplanin的表达,评价淋巴管生成,可能成为预测患者淋巴结转移和病情进展的手段之一.     

Podoplanin increases migration and angiogenesis in malignant glioma

Expression of podoplanin in glial brain tumors is grade dependent. While serving as a marker for tumor progression and modulating invasion in various neoplasms, little is known about podoplanin function in gliomas. Therefore we stably transfected two human glioma cell lines (U373MG and U87MG) with expression plasmids encoding podoplanin. The efficacy of transfection was confirmed by FACS analysis, PCR and immunocytochemistry. Cells were then sorted for highly podoplanin expressing cells (U373P^high/U87P^high). Transfection did not influence the production of pro-angiogenic factors including VEGF, VEGF-C and D. Also, expression of VEGF receptors (VEGFR) remained unchanged except for U87P^high, where a VEGFR3 expression was induced. U373P^high showed significantly reduced proliferation as compared to mock transfected group. By contrast, podoplanin significantly increased migration and invasion into collagen matrix. Furthermore, conditioned media from P^high glioma cells strongly induced tube formation on matrigel. In conclusion, podoplanin increased migration of tumor cells and enhanced tube formation activity in endothelial cells independent from VEGF. Thus, podoplanin expression may be an important step in tumor progression.     

Lymphatic Vessel Density at the Site of Deepest Penetration as a Predictor of Lymph Node Metastasis in Submucosal Colorectal Cancer

Purpose Lymph node metastasis is an important factor that influences curability after endoscopic treatment of submucosal colorectal cancer. This study was designed to determine the usefulness of identification of lymphatic vessels by immunohistochemistry in predicting lymph node metastasis of submucosal colorectal cancer. Methods Lymphatic involvement was assessed by hematoxylin and eosin staining and podoplanin immunostaining on samples resected from 268 patients with submucosal colorectal cancer. Lymphatic vessel density was estimated by two investigators by average count of three fields (×200) in the area of greatest number of podoplanin-positive capillaries at the site of deepest submucosal penetration. Relations with other clinicopathologic parameters also were investigated. Results Lesions with high lymphatic vessel density (≥9 vessels per field) showed a significantly greater incidence of lymph node metastasis than did those with low lymphatic vessel density (<9 vessels per field; 23.3 vs. 8.4 percent). By multivariate analysis, lymphatic vessel density was determined to be an independent risk factor for lymph node metastasis of submucosal colorectal cancer (P = 0.0044). Lymphatic vessel density also correlated with tumor budding and the degree of inflammation at the invasive front. Conclusions Identification of lymphatic vessels by podoplanin immunostaining provides objective and accurate evaluation of lymphatic involvement. Lymphatic vessel density at the site of deepest penetration is a useful predictor of lymph node metastasis of submucosal colorectal cancer. Supported by a grant from the Japanese Society of Gastroenterological Endoscopy, Chugoku Branch. Presented at the meeting of The Japanese Society of Gastroenterology, Kokura, Fukuoka, Japan, April 20 to 22, 2006. Reprints are not available.     

Lymphatic differentiation in renal angiomyolipomas

Renal angiomyolipomas are mesenchymal neoplasms with varying proportions of smooth muscle, adipose tissue, and abnormal blood vessels. Although the presence of lymphangiomatous-like foci is frequently noted in large series of angiomyolipoma, lymphatic differentiation has not been previously studied. Twelve angiomyolipomas from 10 patients were identified. All tumors expressed a melanocytic marker, HMB-45 or Melan-A. Twenty-eight paraffin blocks (1-4 per tumor) were stained for lymphatic endothelial cell markers, podoplanin, and D2-40, and the presence and distribution of lymphatic differentiation were recorded. The angiomyolipomas ranged from typical triphasic tumors to leiomyoma-like and lipoma-like tumors. All 12 tumors showed positive staining with podoplanin, and all 6 tumors stained for D2-40 were also positive, indicative of lymphatic differentiation. Lymphatic differentiation was variably observed throughout the tumors. It was most prevalent in myoid areas of the triphasic angiomyolipomas and in the leiomyoma-like variant, but infrequent and widely scattered within the adipose regions of triphasic angiomyolipoma and in the lipoma-like variant. The lymphatics were usually small, often irregularly shaped, and isolated vessels in fat, whereas in myoid regions lymphatics were clustered and in some areas formed a sinusoidal or labyrinth-like pattern. Lymphatics were commonly adjacent to abnormal arteries. However, unlike the lymphatics in the normal renal cortex, a consistent adventitial association was not observed and the clustering around arteries is regarded as reflecting the myoid regions that typically exist in these areas. In conclusion, lymphatic differentiation is common in angiomyolipomas, preferentially located in myoid regions. These data expand the mesenchymal pluripotential profile of renal angiomyolipomas.     

Type and location of tumor-infiltrating macrophages and lymphatic vessels predict survival of colorectal cancer patients

The type of tumor-infiltrating macrophages may be decisive in tumor immunity, lymphangiogenesis and in the clinical outcome of cancer. Here, we elucidated the prognostic significance of lymphatic vessels, different types of macrophages and the balance between different macrophage types in colorectal cancer. We analyzed the impact of density, type and location of macrophages on the clinical behavior of 159 primary colorectal carcinomas using CD68 as a pan-macrophage marker and CLEVER-1/Stabilin-1 as a marker for regulatory/suppressive macrophages. Podoplanin was used as a pan-lymphatic vessel marker. A high number of CLEVER-1/Stabilin-1(+) peritumoral macrophages positively correlated with survival (p = 0.04). However, in more advanced disease (Stage IV), the patients with a high number of peritumoral or intratumoral CLEVER-1/Stabilin-1(+) macrophages had a shorter disease-specific survival (p = 0.05, and p = 0.008, respectively). Moreover, a low number of suppressive intratumoral CLEVER-1/Stabilin-1(+) macrophages among high numbers of CD68(+) macrophages correlated with a low number of distant recurrences (p = 0.01) and to fewer disease relapses exclusively in the liver as well (p = 0.006). A high number of intratumoral lymphatics correlated with poor survival (p = 0.03). The results of this work suggest that the type of macrophages, number of lymphatic vessels and their location contribute to the clinical behavior of colorectal cancer in a disease stage-specific manner.     

VEGF-C和VEGFR-3在人结肠癌组织中的表达及意义

目的：探讨血管内皮生长因子C（VEGF—C）及其受体3（VEGFR-3）在结肠癌淋巴管生成及淋巴道转移中的作用。方法：取55例人结肠癌组织样本，应用免疫组织化学法，观察VEGF—C和VEGFR-3在人结肠癌组织中的表达，应用Podoplanin标记淋巴管，检测结肠癌组织中的微淋巴管密度。结果：55例结肠癌组织中，VEGF—C阳性表达率为61．8％，明显高于癌周正常组织内的表达（P〈0．05）；结肠癌组织中VEGFR-3表达的阳性率为69．1％，明显高于癌周正常组织（P〈0．01）。经计数淋巴管数量，癌组织中的LMVD明显高于癌周正常组织（P〈0．01），并且LMVD与VEGF—C的表达显著相关（P〈0．01）。结论：VEGF—C通过与VEGFR-3的结合促进癌组织中淋巴管的生成，使癌组织中LMVD增高．对肿瘤细胞发生淋巴道转夥起促进作用。     

乳腺癌中淋巴管密度的研究

 目的 研究原发人类乳腺癌组织中淋巴管密度的变化,并探讨乳腺癌中淋巴管生成(lymphangiogenesis)的情况.方法 随机选取40例乳腺良性病变标本,33例乳腺癌标本及其癌旁"正常腺体",进行免疫组化染色,用兔抗人podoplanin单克隆抗体标记淋巴管,在光镜下观察并计数各标本中的淋巴管密度.结果 乳腺癌组织中podoplanin染色阳性的淋巴管具有壁薄、管腔形状不规则、细胞核突向腔内等特点,与癌旁"正常腺体"和良性病变相比,乳腺癌组织中淋巴管密度均增加,差异均具有统计学意义(P＜0.05).结论 乳腺癌组织中存在淋巴管密度的增加,提示乳腺癌中可能存在淋巴管生成.     

miRNA expression profiling divides follicular dendritic cell sarcomas into two groups,related to fibroblasts and myopericytomas or Castleman's disease

Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumours, which are fatal in 20% of the patients and usually occur in secondary lymphoid organs or extranodal localizations. Due to the rareness of these tumours, only few studies have been conducted on molecular level. In the present study, we performed microRNA (miRNA) profiling of 31 FDC sarcomas and identified two subgroups, one with high miRNA expression and the other group with low miRNA expression levels. The first group showed a strong similarity to fibroblasts and myopericytomas, whereas the second group was more closely related to FDCs from Castleman's disease. Both groups showed important differences compared with myeloid-derived dendritic cells, confirming mesenchymal origin of FDCs and their derived sarcomas. The two FDC sarcoma groups did not differ on morphological grounds, mitotic activity or BRAF mutation status. However, patients of group I presented a tendency to a shorter overall survival and more frequent podoplanin expression by immunohistochemistry. The importance of these newly recognized FDC sarcoma subgroups in terms of clinical behaviour and therapeutic implications should be assessed in a larger cohort in future studies.