Research progress on the mechanism of role of podoplanin in sepsis / 中华危重病急救医学

Podoplanin (PDPN) is a small transmembrane mucin-like glycoprotein which is expressed on the surface of lymphatic endothelial cells, glomerular podocytes, type-Ⅰ alveolar epithelial cells and some tumor cells. PDPN plays crucial function in variety of physiological and pathological processes such as embryonic development, immunoreaction, inflammation and cancer. C-type lectin-like receptor 2 (CLEC2) is mainly expressed on the platelet which specific ligand is PDPN. The interaction between PDPN and CLEC2 has received extensive attention. In this review, we summarized recent researches on the role of in sepsis and elaborated the possible mechanisms and some potential therapies for sepsis by targeting PDPN, which may provide theoretical basis for the mechanism and treatment of sepsis.

Role of twist and podoplanin in partial epithelial-mesenchymal transition in oral squamous cell carcinoma

Abstract The aim of this study was to perform a comparative analysis of podoplanin (PDPN) and Twist immunoexpressions in lower lip and oral tongue squamous cell carcinomas (LLSCC and OTSCC, respectively). PDPN and Twist immunoexpressions were semi-quantitatively evaluated by analyzing the invasion front, the compressive areas, the large islands and nests and dissociated cells of the chosen carcinomas. Their statistical associations and correlations with clinical-pathological characteristics were verified by the Mann-Whitney and Spearman's test. Twist expression was low in both carcinomas, with <25% labeling on the invasive front. Significant differences were observed for LLSCC (p=0.032) and OTSCC (p=0.025) regarding PDPN immunoexpression in relation to the worst invasion patterns determined by a histological malignancy gradation system. Statistically significant negative correlations between PDPN membrane expression and general (r=-0.356, p=0.024) and cytoplasmic Twist expressions (r=-0.336; p=0.034) in LLSCC were also observed. Twist and PDPN are suggested to be associated to a more aggressive invasion pattern in both LLSCC and OTSCC cases but not related to the different biological behaviors on these anatomical sites. Also, it was seen that PDPN membrane expression is inversely related to general and cytoplasmic Twist expression in LLSCC cases.

Resumo O objetivo deste estudo foi realizar uma análise comparativa das imunoexpressões de podoplanina (PDPN) e Twist em carcinomas de células escamosas de lábio inferior e língua oral (CCELI e CCELO, respectivamente). As imunoexpressões de PDPN e Twist foram avaliadas semi-quantitativamente através da análise do front invasivo, das áreas compressivas, das grandes ilhas e ninhos e das células dissociadas dos carcinomas escolhidos. Suas associações estatísticas e correlações com características clínico-patológicas foram verificadas pelos testes de Mann-Whitney e Spearman. A expressão de Twist foi baixa nos dois carcinomas, com marcação <25% no front invasivo. Diferenças significativas foram observadas para CCELI (p=0,032) e CCELO (p=0,025) em relação à imunoexpressão de PDPN em relação aos piores padrões de invasão determinados por um sistema de gradação histológica de malignidade. Também foram observadas correlações negativas estatisticamente significantes entre a expressão membranar de PDPN e as expressões geral (r=-0,356, p=0,024) e citoplasmática do Twist (r=-0,336; p=0,034) no CCELI. Sugere-se que o Twist e o PDPN estejam associados a um padrão de invasão mais agressivo nos casos de CCELI e CCELO, mas não relacionados aos diferentes comportamentos biológicos nesses sítios anatômicos. Também foi observado que a expressão membranar de PDPN está inversamente relacionada à expressão geral e citoplasmática de Twist em casos de CCELI.

Association of the co-expression of SOX2 and Podoplanin in the progression of oral squamous cell carcinomas - an immunohistochemical study

Abstract SOX2 is a transcription factor related to the maintenance of stem cells in a pluripotent state. Podoplanin is a type of transmembrane sialoglycoprotein, which plays an important role in tumor progression and metastasis. This study aims to determine association of SOX2 and podoplanin expression in the progression of oral squamous cell carcinomas and to elucidate the association between two proteins. Methodology: The immunohistochemical expression of SOX2 and podoplanin were evaluated in 60 cases of primary oral squamous cell carcinomas. The correlation between the SOX2 and podoplanin expression and the clinicopathological features of the tumors and the patient outcomes were assessed. Results: The expression of SOX2 was seen in 38/60 (63%) of the cases and the expression for podoplanin was seen in 45/60 (75%) cases. There was a significant inverse correlation between the expression of SOX2 and podoplanin with the tumor grade (p=0.002 and p=0.017, respectively). There was a high expression of SOX2 in 9/13 cases that presented with disease free survival. Survival analysis showed that a high expression of SOX2 correlated positively (p=0.043) with the disease-free survival. There was a significant positive association between the pattern of SOX2 and podoplanin expression (p=0.002). Conclusion: A high expression of SOX2 was associated with better disease-free survival. The expression of podoplanin was associated with the degree of differentiation of the tumors. Analysis of these biomarkers can aid in the prognosis and treatment of oral squamous cell carcinomas.

Stromal podoplanin expression and its clinicopathological role in breast carcinoma

@#Introduction: Breast cancer is still a serious health problem in 21st century and diagnosis, treatment and prognosis of this malignant disease are subject to many research. While cancer research has been focused on tumour cells primarily, recent studies showed that tumour stroma contribute to carcinogenesis as well as tumour cells. Especially fibroblasts adjacent to epithelial tumour cells are not ordinary fibroblasts and play the critical role. Studies showed that these cancer associated fibroblasts (CAFs) have different genetic profile and protein expression. One of the differently expressed molecules recently found is podoplanin. Podoplanin, utilised as a lymphatic endothelial marker, is found to be expressed in CAFs. The aim of this study is to evaluate the relationship between the stromal expression of podoplanin in invasive breast carcinoma and clinicopathological parameters. Materials & Methods: Podoplanin expression was evaluated immunohistochemically in 153 breast cancers. Tumours with ≥ 10% distinct cytoplasmic podoplanin staining in CAFs were considered as positive. Results: In 65.3% of analysed tumours, podoplanin expression was found positive in CAFs. According to our results, podoplanin positive CAFs correlated significantly with tumour size (p= 0.012), tumour grade (p= 0.032) and cerbB2 score (p= 0.032). Discussion: Our results suggest that podoplanin expression by CAFs could predict poor patient outcome in breast carcinoma.

Podoplanin expression and clinical prognosis of patients with esophageal squamous cell carcinoma: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective    To analyze the Podoplanin expression in patients with esophageal squamous cell carcinoma and to find out the relationship between Podoplanin expression and tumor embolus, lymph node metastasis, tumor differentiation as well as prognosis, and to provide clinical evidence for reducing the recurrence of esophageal squamous cell carcinoma and prolonging the disease-free survival and overall survival. Methods    A retrospective analysis of 70 patients with esophageal squamous cell carcinoma in our hospital from June 2010 to June 2012 was conducted, including 39 males and 31 females, with a mean age of 63.6 years. Positive diagnosis of tumor thrombus was achieved in 35 patients and negative in 35 patients. Postoperative pathological specimens were examined and normal esophageal tissues (esophageal tissue more than 5 cm from the edge of the tumor) of patients were excised as a control group. Results    The positive rate of Podoplanin was 34.2% in normal esophageal tissues and 62.8% in tumor tissues. The positive rate of Podoplanin expression was 77.1% and 48.6% in esophageal squamous cell carcinoma patients with or without tumor embolus, respectively. The positive rate of Podoplanin expression in tumor cells of patients with positive and negative lymph node metastasis was 71.9% and 23.1%, respectively (P<0.05). The mean disease-free survival of patients with Podoplanin expression-negative esophageal squamous cell carcinoma was 15.2 months, which was significantly longer than that of patients with Podoplanin expression-positive esophageal squamous cell carcinoma (P<0.05).  Conclusion    Podoplanin expression in the tumor cells and vessels can be an important reference index to the prognosis of patients with esophageal squamous cell carcinoma.

Expresión de Podoplanina en Mucosa Oral Normal, Displasia Epitelial Oral y Carcinoma Oral de Células Escamosas / Immunoexpression of Podoplanin in Normal Oral Mucosa, Epithelial Displasia and Oral Squamous Cell Carcinoma

RESUMEN: Evaluar la inmunoexpresión de podoplanina (PDPN) en el epitelio y vasos linfáticos en muestras de mucosa oral normal (MON), displasia epitelial oral (DEO) y carcinoma espinocelular oral (CECO). Estudio descriptivo de serie de casos. La muestra estuvo constituida por 19 casos de MON, 18 de DEO y 19 de CECO. Se consideraron positivas aquellas células con tinción de membrana y/o citoplasmático. Para la evaluación de PDPN epitelial se realizó un análisis semicuantitativo a través del producto entre la intensidad y porcentaje de células teñidas (immunoreactive score- IRS), mientras que para la evaluación de los vasos linfáticos, se determinó la densidad media vascular (DMV) a partir del promedio de la densidad linfática en tres campos ópticos por muestra. El mayor valor de IRS se observó en el grupo de CECO, seguido por DEO y el menor valor fue en el grupo de MON, con diferencias estadísticamente significativas al comparar CECO/DEO (p= 0,0200) y CECO/MON (p= 0,0078). Al comparar los valores de DMV según diagnóstico, se obtuvo que estos fueron bastante similares y no presentaron diferencias significativas entre sí (p= 0,4273). Finalmente, se analizó la relación entre los valores de IRS de podoplanina epitelial y la densidad media vascular de los linfáticos, a través del test de independencia de Spearman, el cual determinó que no hay un grado de asociación entre ambas variables (p= 0,2056). Conclusión: el IRS epitelial aumenta su valor al comparar muestras de MON, DEO y CECO. No existen diferencias significativas, en las muestras estudiadas, entre los valores de DMV linfática. No existe relación entre la expresión de PDPN epitelial y DMV linfática en muestras de DEO y CECO.

ABSTRACT: The objective of this study was to evaluate the expression of Podoplanin (PDPN) in epithelium and lymphatic vessels in normal oral mucosa (NOM), oral epithelial displasia (OED) and oral squamous cell carcinoma (OSCC). A descriptive case study was carried out. Nineteen histological samples diagnosed with NOM, 18 diagnosed with OED and 19 with OSCC. Immunopositive cells for PDPN were those that presented membrane and/or cytoplasmic staining. A semi-quantitative analysis of the stained sections was made according to the immunoreactive score (IRS) for the extension and intensity of epithelial cells, while the evaluation of lymphangiogenesis was made through the calculation of the mean vascular density (MVD). The results indicated the higher IRS value was in OSCC followed by OED and lowest in NOM, with significant differences between OSCC/OED (p= 0.0200) and OSCC/NOM (p= 0.0078). No differences in MVD were found between the studied samples (p= 0.4273). Finally, the correlation between the value of epithelial IRS and MVD was analyzed through Spearman Independence test, which determined there was no statistically significant relationship between the studied variables (p= 0.2056). In conclusion, epithelial IRS value is greater in OSCC samples than OED and NOM. There was no statistically significant difference in lymphatic MVD in the studied samples. There is no correlation between the epithelial PDPN expression and lymphatic MVD in OSCC and OED samples.

Valor prognóstico da imunoexpressão de podoplanina e de CD44v6 na recidiva locorregional dos pacientes com câncer de lábio / Prognostic value of podoplanin and CD44v6 immunoexpressions on locoregional recurrence of the patients with lip cancer

O objetivo deste estudo consistiu em avaliar a expressão imuno-histoquímica da podoplanina e do CD44v6 pelas células malignas, verificando a associação destas proteínas com as variáveis clínicas, microscópicas, com o índice histopatológico de malignidade e com a sobrevivência livre de doença de 91 pacientes portadores de carcinomas espinocelulares (CEC) de lábio inferior, tratados no Centro de Tratamento e Pesquisa do Hospital do Câncer A.C.Camargo, São Paulo. Os tumores foram corados, separadamente, com os anticorpos anti-podoplanina e anti-CD44v6, sendo avaliada a imunoexpressão destas proteínas pelas células neoplásicas, no front de invasão tumoral, por meio de um método semi-quantitativo de escores. A associação da expressão da podoplanina e do CD44v6 com as variáveis demográficas, clínicas e microscópicas foi feita pelo teste do qui-quadrado ou exato de Fisher. As taxas de sobrevivência livre de doença, acumuladas em cinco e dez anos, foram calculadas pelo teste de Kaplan-Meier e a influência das variáveis clínicas e microscópicas no prognóstico avaliadas pelo modelo de regressão de Cox. A correlação entre a podoplanina e o CD44v6 foi analisada pelo teste de Spearman. Em todos os testes estatísticos utilizou-se um nível de significância de 5%. Os resultados mostraram uma predominância da forte expressão membranosa e citoplasmática da podoplanina pelas células malignas. Verificou-se uma associação significativa da podoplanina citoplasmática com a recidiva locorregional (p=0,028) e da podoplanina membranosa com o índice histopatológico de malignidade tumoral (p=0,026). O CD44v6 foi fortemente expresso pelas células neoplásicas de 95,4% dos CECs e significativamente, associado com o estadiamento clínico T (p=0,034). Não houve correlação entre a podoplanina e o CD44v6 nos CECs de lábio inferior. A forte expressão de podoplanina membranosa (p=0,016) e citoplasmática (p=0,030) pelas células malignas foi fator de prognóstico favorável independente na sobrevivência livre de doença. Concluímos que a podoplanina e o CD44v6 são fortemente expressos pelas células neoplásicas e que a forte imunoexpressão membranosa e citoplasmática da podoplanina pode auxiliar na identificação do risco de recidiva locorregional nos pacientes portadores de carcinoma espinocelular de lábio inferior.(AU)

The aim of this study was evalute the podoplanin and CD44v6 immunohistochemical expression by malignant cells and its association with the clinical and microscopic variables, tumor histopathological grading and disease-free survival of 91 patients with lip squamous cell carcinomas (SCC), submitted to surgical treatment at Research and Treatment Center of the Cancer Hospital A.C. Camargo, São Paulo. The tumors were stained separately, with the antibodies anti-podoplanin and anti-CD44v6, and the immunoexpression of these proteins, by the neoplastic cells in the invasion front, was evaluated by a semi-quantitative scores method. Chi-square test or Fishers exact test was used to analyze the association of podoplanin and CD44v6 expression with demographic, clinical, and microscopic variables. Disease-free survival in five and ten years, were calculated by the Kaplan-Meier method and the influence of clinical and microscopic variables on prognosis were evaluated by the Cox regression model. The correlation between podoplanin and CD44v6 expression was analyzed by Spearman's test and a significance level of 5% was used in all statistical tests. The results showed a predominance of strong membranous and cytoplasmic podoplanin expression by malignant cells. An association between cytoplasmic podoplanin and locorregional recurrence (p=0,028) and membranous podoplanin with tumor histopathological grading (p=0,026). CD44v6 was strongly expressed in 95.4% of the SCCs neoplastic cells and significantly associated with the clinical staging T (p=0,034). There was no correlation between podoplanin and CD44v6 expression in the lower lip SCC. The strong expression of membranous (p=0.016) and cytoplasmic (p=0.030) podoplanin by malignant cells was a favorable independent prognostic factor in disease-free survival. Concluding, the podoplanin and CD44v6 are strongly expressed by neoplastic cells and the strong membranous and cytoplasmic immunoexpression of podoplanin can help the identification of locoregional recurrence risk in patients with squamous cell carcinoma of the lower lip.(AU)

Progress in platelet-activating C-type lectin-like receptor-2 and hematogenous metastasis of tumor / 肿瘤

The process of tumor metastasis is extremely complicated. The growing evidence indicates that platelets are closely involved in hematogenous metastasis of tumors. Platelets can secret an array of bioactive factors to help cancer cells evading immune surveillance and natural killer cell-mediated cytotoxicity, induce epithelialmesenchymal transition (EMT), proliferation, invasion of tumor cells, and subsequently promote cancer progression. Recent studies have showed that the interaction between platelet-activating C-type lectin-like receptor-2 (CLEC-2) and its ligand podoplanin (PDPN) can activate platelets and affect the proliferation, migration, and metastasis of tumor cells. Therefore, using anti-CLEC-2 antibody and blocking the CLEC-2/PDPN interaction maybe the novel anticancer treatments. This review illuminates the role of CLEC-2 in hematogenous metastasis of tumors and its clinical application prospect.

Progress and application of podoplanin's biological functions / 肿瘤研究与临床

Podoplanin (PDPN), being mucin-like transmembrane sialoglycoprotein, is expressed on lymphatic endothelial cells, with its significant role in the development of inflammation, separation of blood and lymphatic circulation, platelet aggregation, integrity of the renal filtration barrier and alveolar. In recent years, many researches have demonstrated that PDPN is overexpressed on the surface of some tumor cells. The interaction between PDPN and CLEC-2 plays an important role in the development of tumor growth, migration and transfer, therefore, anti-PDPN antibody offers a new direction for the treatment of tumor patients. This paper aims at reviewing the progress and application prospect of PDPN.

Role of podoplanin in potentially malignant disorders and oral squamous cell carcinoma and its correlation with lymphangiogenesis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) ranks as one of the most common types of cancer and oral potentially malignant lesions (OPMLs) provides with an overall increased risk for development of carcinoma. As podoplanin expression is attracting interest as a marker for cancer diagnosis and prognosis, this study assesses the role of podoplanin expression in such lesions. MATERIALS AND METHODS: Podoplanin expression and lymphatic vessel density (LVD) was determined using D2‑40, a marker for podoplanin, in 70 diagnosed cases of potentially malignant lesions and OSCC. RESULTS: Normal epithelium showed negligible podoplanin expression, whereas the expression extended predominantly at the basal layer and the suprabasal layer or above at one or multiple areas in potentially malignant lesions. Podoplanin expression in OSCC showed two different patterns‑diffuse and focal. A statistically significant increase in mean LVD was seen from normal epithelium to potentially malignant lesions (P < 0.001) and to OSCC (P < 0.022) while a non‑significant increase was seen (P < 0.594) between OPMLs and OSCC. Overall no significant correlation was found between D2‑40 epithelial positivity and LVD (P = 0.122). CONCLUSION: This study suggests the utility of podoplanin as a biomarker for cancer risk assessment as it detects the early changes and thus provides an additional value beyond current clinical and histopathological evaluations. Hence, podoplanin is suggested to be a marker of tumor initiation and to a lesser extent of tumor progression.

Expression of podoplanin-positive stromal cells in esophageal squamous cell carcinoma and its clinical significance / 临床与实验病理学杂志

Purpose To study the correlation between the expression of podoplanin-positive stromal cells and clinicopathologic features in squamous cell carcinoma ( SCC) of esophagus, and to explore the role of podoplanin-stromal cells in the progression of SCC of e-sophagus. Methods Immunohistochemical EnVision method was used to detect the expression of podoplanin in the stromal cells of e-sophageal SCC. The correlation between the expression of podoplanin-positive stromal cells and clinicopathologic features in SCC of e-sophagus was analyzed. Results Of 69 cases of SCC, podoplanin-positive stromal cells were seen in 43 and the positive rate was 62. 3%. Lymphatic vessel density in SCCs with podoplanin-positive stromal cell was 45. 72 ± 14. 36, which was higher than that with-out podoplanin-positive stromal cell (21. 23 ± 10. 49) (P0. 05). Conclusion Podoplanin-positive stromal cells may promote the lymphangiogenesis and lymph vessel invasion of esophageal SCC.

Are Podoplanin Gene Polymorphisms Associated with Atopic Dermatitis in Koreans?

BACKGROUND: The histologic characteristics of atopic dermatitis (AD) include perivascular edema and dilated tortuous vessels in the papillary dermis. A single nucleotide polymorphism (SNP) of the fms-related tyrosine kinase 4 (FLT4) gene is associated with AD. OBJECTIVE: To investigate the associations between podoplanin (PDPN) gene SNPs and AD. METHODS: We genotyped 9 SNPs from 5 genes of 1,119 subjects (646 AD patients and 473 controls). We determined the promoter activity of 1 SNP (rs355022) by luciferase assay; this SNP was further investigated using 1,133 independent samples (441 AD patients and 692 controls). RESULTS: The rs355022 and rs425187 SNPs and the C-A haplotype in the PDPN gene were significantly associated with intrinsic AD in the initial experiment. The rs355022 SNP significantly affected promoter activity in the luciferase assay. However, these results were not replicated in the replication study. CONCLUSION: Two SNPs and the C-A haplotype in the PDPN gene are significantly associated with intrinsic AD; although, the results were confirmed by luciferase assay, they could not be replicated with independent samples. Nevertheless, further replication experiments should be performed in future studies.

Expression of podoplanin in oral premalignant and malignant lesions and its potential as a biomarker.

Aim: To analyze and compare the expression of podoplanin in normal oral tissues, leukoplakia and oral squamous cell carcinoma (OSCC) and to predict its use as a biomarker. Materials and Methods: Ninety‑two formalin fixed paraffin embedded tissue samples comprising of 32 cases of leukoplakia, 50 cases of OSCCs and ten normal gingival samples. The samples were retrieved from archives and immunohistochemically analyzed using podoplanin. Appendix tissue samples were used for control purposes. The results were tabulated and statistically analyzed using ANOVA/Kruskal–Wallis test with post‑hoc tests, where demographic details are compared and analyzed using Pearson Chi‑square test. Results: The study results showed, absence of podoplanin expression in the epithelium of all the gingival samples (Group I). Positive podoplanin expression noticed in 19 out of 32 (59.4%) cases of leukoplakia (Group II) and 41 out of 50 (82%) cases of OSCCs (Group III). The expression of podoplanin among different groups was highly significant (P = 0.000). Conclusion: The podoplanin may be considered as a predictor marker in assessing malignant transformation of premalignancies and prognosis of oral malignancy. Indeed it is believed that podoplanin might play a role in tumor progression though exact mechanism is not fully elucidated. Further research is required to understand its exact pathophysiology.

Study of the distribution and morphologic feature of the renal lymphatics / 安徽医科大学学报

Objective To observe the fine distribution and morphologic feature of the intrarenal lymphatics. Meth-ods 20 Wistar rats were involved in this study and nephridial tissues were obtained from each animal. Double im-munofluorescence was applied to detect the lymphatic distribution by using Podoplanin and CD34. Renal tissues were obtained from the cortex, medulla and junctional zone,and put in 3% glutaric dialdehyde stationary liquid for transmission electron microscope to observe the fine distribution and morphologic feature of the intrarenal lymphat-ics. Results Under immunofluorescence double staining, lymphatic capillary appeared anomalism, large lumina, thin wall and located in connective tissue region. Cortilymph obviously exceeded medulla lymph in rats. Under e-lectron microscope, the basal lamina of lymphatic was discontinuity. A lot of lysosome and vesicles existed in the endothelial of capillary lymphatics. Many of the vesicles liberated in cytoplasm. The intercellular junctions of the renal lymphatics were held in close apposition. Conclusion The intercellular junctions of the renal lymphatics are held in close apposition by adhesion devices. A lot of lysosomes and vesicles exist in the endothelial of capillary lymphatics, which are the base for renal to transport big molecules and fluids.

Podoplanin, alpha-Smooth Muscle Actin or S100A4 Expressing Cancer-Associated Fibroblasts Are Associated with Different Prognosis in Colorectal Cancers

The interactions between the tumor microenvironment and tumor cells determine the behavior of the primary tumors. Whether cancer-associated fibroblasts (CAF) have a tumor progressive or a protective role likely depends on the type of tumor cells and the CAF subpopulation. In the present study, we analyzed the prognostic significance of CAF subpopulations in colorectal cancer (CRC). CAF phenotypes were analyzed in 302 CRC patients by using antibodies against podoplanin (PDPN), alpha-smooth muscle actin (alpha-SMA), and S100A4. The relationship between the CAF phenotypes and 11 clinicopathological parameters were evaluated and their prognostic significance was analyzed from the disease-free and overall survival times. We observed that at the tumor invasive front, PDPN CAFs were present in 40% of the cases, and S100A4 or alpha-SMA CAFs were detected in all the cases. PDPN/S100A4 and alpha-SMA/S100A4 dual-stained CAFs were observed in 10% and 40% of the cases, respectively. The PDPN+ CAFs were associated with 6 favorable clinicopathological parameters and prolonged disease-free survival time. The PDPN-/alpha-SMA(high) CAFs were associated with 6 aggressive clinicopathological parameters and tended to exhibit shorter disease-free survival time. On the other hand, the PDPN-/S100A4(high) CAFs were associated with 2 tumor progression parameters, but not with disease prognosis. The PDPN+ CAF phenotype is distinct from the alpha-SMA or S100A4 CAFs in that it is associated with less aggressive tumors and a favorable prognosis, whereas the PDPN-/alpha-SMA(high) or PDPN-/S100A4(high) CAFs are associated with tumor progression in CRC. These findings suggest that CAFs can be a useful prognostic biomarker or potential targets of anti-cancer therapy in CRC.

Expression of endoglin and podoplanin in early and advanced oral squamous cell carcinoma

OBJECTIVES: Angiogenesis and lymphangiogenesis are correlated with tumor growth and lymph node metastasis in cases of oral squamous cell carcinoma (OSCC). Endoglin is one of the representative vascular endothelial cell markers. Podoplanin is also a representative marker used in order to detect lymphatic endothelial cells. The aim of this study was to determine the correlation between the expression of endoglin/podoplanin and clinical variables associated with OSCC progression. MATERIALS AND METHODS: Paraffin embedded tissue specimens from 21 patients diagnosed with OSCC were used in this study. Ten patients were diagnosed with early clinical stage (I or II) and 11 patients with advanced clinical stage (III or IV) OSCC. Five patients had positive lymph node involvement. Primary antibodies for endoglin and podoplanin were used to perform the immunohistochemical detection of the vascular and lymphatic endothelial cells. The expression of endoglin and podoplanin was examined by an image analysis program in the three most highly expressed regions of each specimen. RESULTS: The average endoglin expression was observed to be 1.691+/-0.920 in the advanced stage (III, IV) specimens and 0.797+/-0.583 in the early stage (I, II) specimens (P=0.020). The average expression of podoplanin was 0.286+/-0.228 in the advance stage (III, IV) specimens and 0.374+/-0.157 in the early stage (I, II) specimens (P>0.05). There was no statistically significant difference in the expression of endoglin and podoplanin, regardless of whether or not the lymph node was positive. CONCLUSION: The expression of endoglin was significantly higher in the advanced stage specimens than that in the early stage specimens. Therefore, we concluded that endoglin is a useful molecular marker for use in the evaluation of the progression of OSCC.

Pathologic characteristics of lymphangiogenesis in renal transplants and its clinical implication / 第二军医大学学报

Objective: To investigate the pathologic characteristics of lymphangiogenesis in renal transplants and to analyze its clinical implication. Methods: The morphology and distribution of lymphangiogenesis were investigated by a biotin-streptavidin horseradish-peroxidase method with anti-podoplanin monoclonal antibody in 45 archival biopsies. The lymphatic vessel density (LVD) was calculated and the results were compared between different pathologic types and with the normal renal tissues. Results: Fewer podoplanin-positive lymphatic vessels were identified in the biopsies from the renal transplants with normal function, and the transplants had a similar morphological profile as normal renal tissues. More podoplanin-positive lymphatic vessels were observed in the transplants suffering acute rejection episode; the vessels mainly located around peripheral arteriole with different lumen sizes. Transplants with chronic rejection had the most podoplanin-positive lymphatic vessels with focal mononuclear infiltration and distended/ distorted lymphatic vessels. The lowest mean LVD (1.26±0.27) was observed in the biopsies from transplants with normal function, which was significantly different from those in the acute rejection and chronic rejection groups (P<0.05). The highest mean LVD was found in the chronic rejection group (20.76±5.30), which was significantly higher than those of the other 2 groups (P<0.01); no significant difference was observed between the transplants with normal function and the normal kidney. Conclusion: Lymphatic neoangiogenesis occurs in the renal transplant and its pathologic characteristics differs in the transplants with different rejection types.

Neoplasias salivares com diferenciação mioepitelial: estudo da imunoexpressão do CD10 (CALLA/NEP 24.11) e da podoplanina (D2-40) / Salivary neoplasias with myoepithelial differentiation

CD10 e Podoplanina (D2-40), além de expressos nas células mioepiteliais, estão envolvidos na progressão tumoral e podem ser utilizados como marcadores prognósticos. Em 79 neoplasias salivares com diferenciação mioepitelial (44 malignas e 35 benignas), analisamos a expressão dessas proteínas nas células neoplásicas, na reação desmoplásica tumoral e, nos carcinomas adenóides císticos (CAC), verificamos possível correlação com fatores prognósticos. CD10 foi negativo nas células epiteliais em 100 por cento dos casos. Nas mioepiteliais, foi positivo em 25,71 por cento das lesões benignas e em 27,27 por cento das malignas, sendo esses resultados significantemente inferiores àqueles da a-SMA (60 por cento e 88,64 por cento, respectivamente). CD10 foi positivo em 83,33 por cento, 30 por cento, 27,7 por cento e 40 por cento dos carcinomas epiteliais-mioepiteliais (CEME), adenomas pleomórficos, mioepiteliomas e carcinomas mioepiteliais, respectivamente, e negativo em 100 por cento dos CAC, adenocarcinomas polimórficos de baixo grau (APBG) e adenomas de células basais. No estroma tumoral, a expressão do CD10 (38,64 por cento) foi significantemente...

CD10 and Podoplanin (D2-40) are expressed in myoepithelial cells and, in addition, are involved in tumoral progression and can be utilized as prognostic markers. In a series of 79 salivary neoplasias with myoepithelial differentiation (44 malignant and 35 benign), the expression of these proteins was analyzed in tumor cells as well as in tumor-associated stromal cells and it was correlated with prognostic factors in a select group of lesions (adenoid cystic carcinomas). In epithelial cells, CD10 was negative in 100 per cent of the cases. In myoepithelial cells, CD10 was positive in 25.71 per cent of the benign neoplasias and in 27.27 per cent of the malignant ones and this expressions was significantly lower in comparison to that of a-smooth muscle actin (a-SMA) (60 per cent and 88.64 per cent, respectively). In neoplasias classified according to histological subtype, CD10 was positive in 83.33 per cent, 30 per cent, 27.27 per cent and 40 per cent of epithelial-myoepithelial carcinomas (EMC), pleomorphic adenomas, myoepitheliomas and myoepithelial carcinomas, respectively...

Expression and clinical significance of Bmi-1,Podoplanin and p53 in human thymic epithelial tumor / 上海第二医科大学学报

Objective To investigate the expression and clinical significance of Bmi-1,Podoplanin and p53 in human thymic epithelial tumor(TET) according to new histological classification of World Health Organization. Methods One hundred and ten TET tissue chips were prepared,and the expressions of Bmi-1,Podoplanin and p53 were detected by NovoLinkTM Polymer detection systems. Results The positive expressions of Bmi-1,Podoplanin and p53 were 68.2%,41.8% and 42.7%,respectively.The positive expressions of Bmi-1,Podoplanin and p53 were significantly associated with pathologic histological classification,Masaoka staging and clinic pathological grading(P

The Investigation of the Relation Between the Expression of Podoplanin and the Lymphatical Metastasis in the Human Colonic Carcinoma / 医学研究杂志

Objective To provide the morphology data for the study on the molecular mechanism of tumor metastasis,we observed the expression of podoplanin on the blood vessels and lymphatics in the human colonic carcinoma.Methods We observed the expression of podoplanin on the blood vessels and lymphatics in the colonic carcinoma from the patients of the operation in the defferent stages with the methods of HE staining and podoplanin immunohistochemistry staining. Results Podoplanin has not been stained,but podoplanin was positively expressed on the colonic carcinoma lymphatics.And, The podoplanin expression positive rate of the colonic carcinoma were increased along with the increase of tumor stages and occurence of lymph nodes metastasis. Conclusion Podoplanin choosed to express in lymphatics in the colonic carcinoma and could correctly distinguish the blood vessels and lymphatic vessels,could be regarded as the specific marker to mark lymphatic vessel. And, The podoplanin expression positive rate of the colonic carcinoma were increased along with the increase of tumor stages and occurence of lymph nodes metastasis.It indicates,It was correlated with colonic carcinoma lymphatical metastasis that the count of lymphatic vessels were increased in the colonic carcinoma along with the tumor advancing.