Podoplanin expression predicts prognosis in patients with oral squamous cell carcinoma treated with neoadjuvant radiochemotherapy

Despite new therapeutic approaches patients with advanced oral squamous cell carcinoma still have a dismal prognosis. The main factor contributing to this problem is locoregional failure due to a lack of response to treatment. Several trials have proven the effect of neoadjuvant radiochemotherapy followed by radical surgery in comparison to primary surgery followed by adjuvant radiochemotherapy. No reliable parameters have been identified so far to predict response to radiochemotherapy. The aim of our study was to assess whether podoplanin expression in pretreatment biopsies could serve as a biomarker to predict the host response to neoadjuvant radiochemotherapy.In this retrospective study, podoplanin expression was examined in a set of 63 patients with oral squamous cell carcinoma by immunohistochemistry. We analyzed associations between the level of podoplanin expression and various clinicopathologic parameters, including response to radiochemotherapy, clinical and histological N-status. Furthermore we evaluated the effects of these parameters on overall survival and on locoregional control in univariate and multivariate analysis.The χ²-test revealed that high expression of podoplanin in pretreatment biopsy material was associated with non-regression of the tumor (p = 0.013) and poor overall survival (p < 0.001). Five-year survival rates of 92.9% for patients with weak expression and 15.0% for high expression were revealed. Podoplanin expression was also significantly associated with ypN status (p = 0.004) and ypUICC status (p < 0.001).We concluded that podoplanin might serve as a factor to predict treatment response in oral squamous cell carcinoma treated with neoadjuvant platin-based radiochemotherapy as well as a prognostic factor for overall survival and locoregional control.     

血管内皮生长因子C及Podoplanin在人食管癌组织中的表达

目的研究血管内皮生长因子C（VEGF—C）及Podoplanin在食管癌组织中的表达及意义。方法取临床手术切除的50例食管癌组织,用免疫组化方法检测食管癌中VEGF—C及Podoplanin的表达情况。结果在食管癌的癌细胞中可见VEGF—C阳性表达,阳性颗粒主要定位于肿瘤细胞胞浆内,并且进展期食管癌中VEGF-C表达明显高于早期,VEGF-C的表达与患者的性别、年龄无关（P〉0．05）,而与有无淋巴结转移密切相关（P〈0．01）。Pndoplanin只表达于淋巴管内皮细胞,进展期食管癌组织微淋巴管密度（LMVD）明显高于早期食管癌组织（P〈0．01）。结论食管癌癌细胞VEGF—C的表达与肿瘤进展呈正相关,提示VEGF—C可促进食管癌组织淋巴管生成,从而引起癌细胞经淋巴道转移。Podoplanin可作为淋巴管的特异性标记物之一。     

Podoplanin expression as a predictive marker of dysplasia in oral leukoplakia

Purpose

Recent studies have emphasized the role of podoplanin in oral lesions at risk of malignant transformation. We investigated a group of oral leukoplakias (OLs) to determine a possible relation between altered podoplanin expression and dysplasia, and to compare the results with those obtained by other, widely used biomarkers.

Podoplanin expression in primary central nervous system germ cell tumors: a useful histological marker for the diagnosis of germinoma

Podoplanin, a mucin-like transmembrane sialoglycoprotein, promotes platelet aggregation and may be involved in cancer cell migration, invasion, metastasis, and malignant progression. Podoplanin/aggrus is highly expressed in testicular seminoma, suggesting that it may be a sensitive marker for testicular seminomas. Here we investigated the expression of podoplanin in central nervous system (CNS) germ cell tumors (GCTs) by immunohistochemical staining of tumor samples from 62 patients. In 40 of 41 (98%) germinomas (including germinomatous components in mixed GCTs), podoplanin was diffusely expressed on the surface of germinoma cells; lymphocytes, interstitial cells, and syncytiotrophoblastic giant cells were negative for podoplanin. Except for immature teratomas (12/17; 71%), podoplanin expression was absent in non-germinomatous GCTs, including seven teratomas, seven embryonal carcinomas, seven yolk sac tumors, and seven choriocarcinomas. In immature teratomas, focal podoplanin staining was observed in fewer than 10% of immature squamous and columnar epithelial cells. Thus, podoplanin expression may be a sensitive immunohistochemical marker for germinoma in CNS GCTs. As such, it may be useful for diagnosis, for monitoring the efficacy of treatment, and as a potential target for antibody-based therapy.Kazuhiko Mishima and Yukinari Kato contributed equally to this work.     

Podoplanin (d2-40): a new immunohistochemical marker for reactive follicular dendritic cells and follicular dendritic cell sarcomas

The diagnosis of follicular dendritic cell (FDC) sarcoma can be challenging because of its morphologic overlaps with many other spindle cell neoplasms and, therefore, new phenotypic markers will be helpful in its differential diagnosis. Podoplanin is a mucin-type transmembrane glycoprotein that has recently been detected in reactive FDCs. In this study, we investigated the expression patterns of podoplanin using a new mouse monoclonal antibody D2-40, and compared them with CD21, a well-established FDC marker, in a comprehensive panel of cases. The panel included 4 FDC sarcomas, 38 spindle cell neoplasms of other types, 25 reactive lymphoid hyperplasia, and 117 lymphoid and 5 myeloid malignant hematopoietic neoplasms. Our study revealed that D2-40 strongly stained 3 of 4 FDC sarcomas. In contrast, D2-40 stained only 2/38 other spindle cell neoplasms tested. Furthermore, we observed that D2-40 highlighted more FDC meshworks than CD21 in Castleman's disease, follicular lymphoma, nodular lymphocyte predominance Hodgkin lymphoma, and residual reactive germinal centers in a variety of lymphoma types. D2-40 and CD21 stained an equal number of cases of reactive lymphoid hyperplasia, progressively transformed germinal centers and angioimmunoblastic T-cell lymphoma. No expression of podoplanin was detected in normal or neoplastic lymphoid and myeloid cells. We conclude that podoplanin (D2-40) is a sensitive and specific FDC marker, which is superior or equal to CD21 in evaluating both reactive and neoplastic FDCs. In addition, our results suggest that podoplanin (D2-40) can be used to support the diagnosis of FDC sarcoma.     

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 the mouse salivary glands

OBJECTIVE: Podoplanin is one of the most highly expressed lymphatic-specific genes. Here, we report the distribution of cells expressing podoplanin in mouse salivary glands. DESIGN: We immunohistochemically investigated the distribution of cells expressing podoplanin in mouse major salivary glands by laser-scanning microscopy. The expression of endothelial cell marker PECAM-1 was tested to discriminate lymphatic endothelium from salivary gland cells, and myoepithelial cells were identified by an antibody for P-cadherin. RESULTS: The podoplanin expression was rarely found in acini of the parotid gland but clearly found at the basal portion of acini in the submandibular and sublingual glands. The number of portion reacted with anti-podoplanin is greater in the sublingual gland than in the submandibular gland. The expression was also found at the basal portion of ducts in all major salivary glands. The P-cadherin expression was rarely found in acini of the parotid gland but found in acini of the sublingual gland and on ducts in parotid and sublingual glands, corresponding to the area of podoplanin expression. CONCLUSIONS: It was suggested that the acinar and myoepithelial cells in the salivary glands have the ability to express podoplanin, and that the expression may be concerned with the mucous saliva excretion.     

Endothelial follicle-stimulating hormone receptor expression in invasive breast cancer and vascular remodeling at tumor periphery

Background

Follicle-stimulating hormone receptor (FSHR) is expressed on the endothelial surface of blood vessels associated with solid tumor periphery, where angiogenesis is known to occur. The correlation between FSHR expression and formation of new peritumoral vessels has not been previously investigated.

Methods

We used immunohistochemical techniques involving specific antibodies to detect FSHR and the endothelial markers (CD34, VEGFR2, and D2-40) in tissue samples from 83 patients with lymph node-negative, invasive breast cancer representing four main clinical treatment groups: HR+/HER2-, HR+/HER2+, HR-/HER2+ and triple-negative.

Results

The FSHR+ vessels were exclusively located at breast cancer periphery, in a layer that extended 2 mm into and 5 mm outside of the tumor. The percentage of blood vessels expressing FSHR reached a maximum of 100% at the demarcation line between the tumor and the normal tissue. Common among FSHR+ vessels, regardless of breast cancer type, were the high densities of arterioles and venules (6.4 ± 1.4 and 13.9 ± 2.1 vessels/mm², respectively). These values were 3-fold higher that those noticed for CD34+ arterioles and venules associated with normal breast tissue located at a distance greater than 10 mm outside the tumors. The average density of FSHR+ and CD34+ blood vessels as well as of D2-40+ lymphatic vessels did not differ significantly among breast cancer subgroups. FSHR+ vessels did not express VEGFR2. The endothelial FSHR expression correlated significantly with the peritumoral CD34+ vessels’ density (p < 0.001) and tumor size (p = 0.01).

Conclusion

Endothelial FSHR expression in breast cancer is associated with vascular remodeling at tumor periphery.     

血小板源性生长因子受体-β、Podoplanin在非小细胞肺癌间质中的表达与癌相关成纤维细胞及淋巴管生成的关系

目的探讨血小板源性生长因子受体-β(PDGFR-β)、Podoplanin在非小细胞肺癌(NSCLC)间质中的表达与癌相关成纤维细胞(CAFs)和淋巴管生成的关系。方法采用免疫组织化学Elivision二步法,检测80例NSCLC患者间质及20例癌旁正常肺组织间质中PDGFR-β、Podoplanin的表达,用肌动蛋白α(α-SMA)标记CAFs,D2-40标记微淋巴管,计数微淋巴管密度(LMVD),分析PDGFR-β、Podoplanin表达情况及与CAFs、LMVD和临床病理参数之间的关系。结果 NSCLC中PDGFR-β、Podoplanin在间质中的表达均高于癌旁正常肺组织(P均<0.05)。NSCLC间质中PDGFR-β与Podoplanin的表达呈正相关(r=0.380,P<0.05),且其表达与CAFs密切相关。癌组织中LMVD明显高于癌旁正常肺组织(P<0.05);且淋巴结转移组LMVD更高(P<0.05);PDGFR-β或Podoplanin阳性表达组LMVD明显高于阴性表达组(P均<0.05)。间质中PDGFR-β的阳性表达与患者组织分化程度相关(P<0.05)。Podoplanin的阳性表达与组织分化程度和淋巴结的转移相关(P均<0.05)。结论 PDGFR-β、Podoplanin在NSCLC间质中的表达与CAFs有关,且与肿瘤淋巴管的形成密切相关。