High-level expression of CD109 is frequently detected in lung squamous cell carcinomas

CD109 is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein, which is a member of the alpha2-macroglobulin/C3, C4, C5 family of thioester-containing proteins. It has been reported that CD109 is expressed in a subset of hematopoietic cells, endothelial cells and several kinds of human tumors. Herein it is reported that the CD109 protein is preferentially expressed in lung squamous cell carcinomas compared with other types of lung carcinoma including adenocarcinomas, large cell carcinomas and small cell carcinomas. Immunohistochemical staining of surgically resected lung specimens using an anti-CD109 antibody detected CD109 expression in basal cells of bronchial and bronchiolar epithelia and myoepithelial cells of bronchial secretary glands, but not in bronchial and bronchiolar apical epithelial cells and alveolar epithelial cells. Furthermore, the CD109 immunoreactivity was observed in squamous cell carcinomas at a high frequency compared with other types of lung carcinoma. Although the detailed function of CD109 protein is unclear, these results suggest that CD109 expression may play a role in the development of lung squamous cell carcinoma.     

CD117和Nestin在卵巢上皮性癌组织中的表达及临床意义

目的检测CD117及Nestin在卵巢上皮癌（EOC）中的表达水平,并探讨其临床意义。方法选择河北省邯郸市中心医院病理存档的石蜡标本80份,其中20份为正常卵巢标本,60份为卵巢上皮癌标本,采用免疫组化法（SP法）检测其CD117及Nestin的表达水平,并分析其与临床病理因素之间的关系。结果 CD117及Nestin在正常卵巢组织和卵巢上皮癌中的阳性表达率分别为10.0%、65.0%和5.0%、38.3%,差异有统计学意义（P〈0.05）。CD117及Nestin在EOC组中的表达水平与其FIGO分期及病理分级有关,在Ⅲ-Ⅳ期、低分化组（G3）比Ⅰ-Ⅱ期、高中分化（G1、G2）组表达率高（P〈0.05）。通过Kaplan-Meier生存曲线了解CD117和Nestin在预测卵巢癌预后中的价值。结论CD117与Nestin在卵巢上皮性癌中高表达,CD117及Nestin可能促进了卵巢上皮癌的发生、发展,并可能作为卵巢癌干细胞标志物用于判断卵巢上皮性癌的预后。     

CD44v6与MMP—9在口腔鳞癌中的表达意义

目的：探讨细胞粘附分子CD44v6和基质金属蛋白酶MMP－9相互关系及其在评估口腔鳞癌的组织学分级,肿瘤浸润以及转移等生物学特性中的意义。方法：运用免疫组化S－P法测定22例口腔鳞癌和6例正常口腔黏膜组织中CD44v6和MMP－9的表达,结果：CD44v6在正常口腔黏膜组织呈强阳性表达;癌组织中CDv6的表达明显弱于正常组织,高表达CD44v6的口腔鳞癌不仅分化程度较差而且易发生淋巴结转移,MMP－9在正常口腔黏膜组织中呈阴性或弱阳性表达,癌组织中MMP－9的阳性表达高达68．2％（15／22）。MMP－9的表达与病理分级和颈淋巴结转移呈正相关（P＜0．05）,口腔鳞癌中MMP－9与CD44v6的表达呈正相关（P＜0．01）,多因素分析示两者之间的交互作用是影响口腔鳞癌病理分化和颈淋巴结转移的最重要因素。结论：口腔鳞癌中CD44v6与MMP－9的表达密切相关。MMP－9和CD44v6可作为临床上评估口腔鳞癌浸润,转移以及预后的指标。     

Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome

Cancer stem cells (CSCs) play an important role in the recurrence and drug resistance of cancer. Isolation and characterization of CSCs from ovarian cancer samples may help to provide novel diagnostic and therapeutic targets in the management of recurrent disease and drug resistance in ovarian cancer. Here, we developed a xenograft model in which cells from 14 samples of human ovarian serous adenocarcinoma tissue or ascites were implanted in immunodeficient mice to test the tumorigenic potential of different populations of ovarian cancer cells. We identified and isolated the tumorigenic cells as CD117⁺Lineage⁻ from three different xenografts. As few as 10³ cells with the CD117⁺Lineage⁻ phenotype, which comprise < 2% of the xenograft tumor cells, were able to regenerate tumors in a mouse model, a 100-fold increase in tumorigenic potential compared to CD117⁻Lineage⁻ cells. The tumors that arose from purified CD117⁺Lineage⁻ cells reproduced the original tumor heterogeneity and could be serially generated, demonstrating the ability to self-renew and to differentiate, two defining properties of stem cells. Furthermore, immunohistochemistry analysis of 25 patients with advanced ovarian serous adenocarcinoma revealed positive immunostaining for CD117 in 40% (10 of 25) of patients. CD117 expression was statistically correlated with resistance to conventional chemotherapy (P = 0.027). In conclusion, our study demonstrates that human ovarian cancer cells with the CD117⁺ phenotype possess the unique properties of CSCs, including self-renewal, differentiation, a high tumorigenic potential, and chemoresistance. Future studies designed to target CD117⁺ cancer cells may identify more attractive and effective therapies for treatment of ovarian cancer.     

非小细胞肺癌中CD44v6的表达

目的　探讨CD4 4v6表达与非小细胞肺癌临床病理特征之间的关系。方法　采用免疫组化S P法检测 132例非小细胞肺癌、6 6例淋巴结转移癌和 115例正常肺组织CD4 4v6表达的情况。结果　非小细胞肺癌CD4 4v6阳性表达率为4 8 4 8% ,高于正常肺组织 17 39%的阳性表达率。CD4 4v6阳性表达与淋巴结转移状况、TNM分期、肿瘤大小和组织学类型有相关性。非小细胞肺癌淋巴结转移组、TNMⅢ期患者、直径 >3cm的肿瘤和鳞癌CD4 4v6阳性表达率分别高于无淋巴结转移组、TNMⅠ期和Ⅱ期患者、直径≤ 3cm的肿瘤和腺癌。淋巴结转移癌CD4 4v6阳性表达率高于肺原发癌。CD4 4v6阳性表达与患者的性别、年龄和组织学分级无相关性。结论　CD4 4v6阳性表达预示非小细胞肺癌具有较强的侵袭和转移能力 ,可作为一项预测非小细胞肺癌转移潜能生物学指标。     

Radiation sensitivities of 31 human oesophageal squamous cell carcinoma cell lines

The purpose of this study was to determine the radiosensitivities of 31 human oesophageal squamous cell carcinoma cell lines with a colony-formation assay. A large variation in radiosensitivity existed among 31 cell lines. Such a large variation may partly explain the poor result of radiotherapy for this cancer. One cell line (KYSE190) demonstrated an unusual radiosensitivity. Ataxia-telangiectasia-mutated (ATM) gene in these cells had five missense mutations, and ATM protein was truncated or degraded. Inability to phosphorylate Chk2 in the irradiated KYSE190 cells suggests that the ATM protein in these cells had lost its function. The dysfunctional ATM protein may be a main cause of unusual radiosensitivity of KYSE190 cells. Because the donor of these cells was not diagnosed with ataxia telangiectasia, mutations in ATM gene might have occurred during the initiation and progression of cancer. Radiosensitive cancer developed in non-hereditary diseased patients must be a good target for radiotherapy.     

Immunohistochemical expression of aminopeptidase N (CD13) in human lung squamous cell carcinomas, with special reference to Bestatin adjuvant therapy

Bestatin, a specific inhibitor of aminopeptidase N (CD13), has been reported to prolong survival time in patients with completely resected stage I lung squamous cell carcinoma. Considering the antitumor mechanism of Bestatin, it is interesting to know whether CD13 is expressed in human lung squamous cell carcinoma. The immunohistochemical expression of CD13 was examined in human lung carcinoma and the question of whether CD13 was immunohistochemically expressed in the interstitial tissue was investigated, mainly in the fibroblasts and blood vessels, surrounding the tumor nests of various kinds of non-small cell lung cancers, especially of squamous cell carcinomas. In Japanese squamous cell carcinoma of the lung, 38 (61.3%) out of 62 cancers were positively stained in the same manner on immunohistochemistry for CD13. The area of interstitial tissue positively stained for CD13 varied depending on the case. To confirm the cell nature of the interstitial tissue with CD13 positivity, double immunohistochemistry using CD34 and alpha-smooth muscle actin was performed. Double immunohistochemistry showed that the majority of CD13-positive cells were slender fibroblastic cells around the blood vessels and some endothelial cells.     

The telomere/telomerase binding factor PinX1 is a new target to improve the radiotherapy effect of oesophageal squamous cell carcinomas

Chemoradiotherapy (CRT) is a standard treatment for oesophageal squamous cell carcinoma (ESCC) in its advanced stages. The telomerase/telomere interacting protein PinX1 contributes to telomere maintenance, tumourigenicity, and influences the DNA damage agent‐induced apoptotic response in telomerase‐positive cancer cells. However, the clinical and biological significance of PinX1 in human ESCCs remains unclear. We examined the expression dynamics of PinX1 by immunohistochemistry in a learning cohort (n = 98) and a validation cohort (n = 59) of ESCC patients treated with definite chemoradiotherapy (CRT). A series of in vivo and in vitro assays were performed to elucidate the effect of PinX1 on ESCC cells' CRT response and underlying mechanisms. Knockdown of PinX1 did not affect ESCC cells' chemosensitivities to 5‐fluorouracil and cisplatin, but substantially increased ESCC cells' therapeutic efficacy of radiation both in vitro and in vivo. Ectopic overexpression of PinX1 dramatically enhanced ESCC cells' resistance to radiotherapy. Furthermore, we demonstrated that PinX1 resistance to radiotherapy (RT) was attributed to PinX1 maintaining telomere stability, reducing ESCC cell death by RT‐induced mitosis catastrophe (MC). High expression of Pinx1 correlated positively with ESCC's resistance to CRT, and was a strong and independent predictor for short disease‐specific survival (DSS) of ESCC patients. Our data suggest that PinX1 could serve as a novel predictor for a CRT response to ESCC patients, and the pathway of PinX1‐mediated telomere stability might represent a new target to improve the RT effect of ESCC. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

PINCH expression and its significance in esophageal squamous cell carcinoma

Particularly interesting new cysteine-histidine rich protein (PINCH), as a newly discovered protein of LIM family members, may play a role in signal transduction of integrin and growth factor, and involved in the incidence and development of tumors. PINCH protein is overexpressed in tumor-associated stroma of several types of tumors. However, there is no study of the PINCH in esophageal cancer, therefore we investigated PINCH expression in esophageal squamous cell carcinomas and its clinicopathological significance in the patients. PINCH expression was immunohistochemically examined in 20 normal esophageal samples and 64 esophageal squamous cell carcinomas. The results showed that PINCH expression in the stroma of cancers was heterogeneous, and its positive rate (56%) was higher than that of normal esophageal mucosa (5%, p<0.0001). The stronger staining was observed at the invasive edge of tumor when compared to the inner area of tumor. The rate of positive PINCH (90%) in the cases with lymph node metastasis was higher than that (41%) in the cases without metastasis (p<0.0001). PINCH expression was not correlated with patients' gender, age, tumor location, size and differentiation (p>0.05). The results suggest that PINCH protein may be a marker of tumor associated-stroma involving tumor development, and predicting the ability of invasion and metastasis of esophageal squamous cell carcinoma.     

Gli1 expression in cancer stem-like cells predicts poor prognosis in patients with lung squamous cell carcinoma

Purpose

Glioma-associated oncogene homolog 1 (Gli1) is involved in cancer stem cell (CSC) maintenance in various tumors; however, its expression and clinical significance in lung squamous cell carcinoma (LSCC) has not been reported. In this study, we aimed to reveal the clinical significance of Gli1 in LSCC and investigate the potential of Gli1 as a CSC marker by comparing its expression with that of other stemness-related genes in LSCC.

Immunohistochemical expression of CD117 and vascular endothelial growth factor in retinoblastoma: possible targets of new therapies

CD117 (C-kit) is thought to play an important role in tumourigenesis. There are limited data in the literature concerning C-kit expression in retinoblastoma. To date, no immunohistochemical studies have been performed to assess the possible association of C-kit with vascular endothelial growth factor (VEGF) in retinoblastoma. This study was designed to investigate C-kit and VEGF immunoexpression in retinoblastoma, their relationship with prognostic parameters as well as the correlation between them. A prospective immunohistochemical study was conducted on 56 retinoblastoma cases. Patients who had received preoperative chemotherapy were excluded. Positive C-kit and VEGF immunoreactivity was observed in 48.2% and 76.8% of retinoblastoma cases respectively. No C-kit immunostaining was seen in the adjacent uninvolved retina. However, VEGF expression was detected within its vasculature. Retinoblastomas with combined pattern of tumour growth revealed a highly significant positive C-kit expression (P = 0.002) compared to cases with endophytic or exophytic growths. Also, positive C-kit expression was statistically higher in cases with optic nerve invasion (P = 0.001) and choroidal invasion (P ≤ 0.01) compared to negative cases. A highly significant positive VEGF expression was detected in cases with optic nerve invasion (P = 0.013) compared to negative cases. Moreover, a highly significant positive correlation was detected between C-kit and VEGF expression (P = 0.006). C-kit is a feature of more aggressive retinoblastomas, with increased expression in tumours spreading beyond the retina. Moreover, VEGF is vastly expressed in retinoblastoma and is associated with optic nerve invasion. Both C-kit and VEGF may represent potential therapeutic targets for retinoblastomas.     

Prognostic value of CD117 in cancer: a meta-analysis

Background: The prognostic value of CD117 expression in cancers has been evaluated for several years while the results remain controversial. We thus performed a systematic review and meta-analysis of studies assessing the impact of CD117 expression on overall survival (OS) and disease-free survival (DFS) to clarify this issue. Methods: We searched Pubmed, Embase and Web of Science to identify studies on the prognostic impact of CD117 expression in cancers. A total of 4,458 patients from 39 eligible studies were included in the analysis. Pooled risk ratios (RRs) with 95% confidence interval (95% CI) were calculated to estimate the effect using random-effects model. Results: The analysis indicated that CD117 had significant association with poor OS of osteosarcoma (OR=1.36, 95% CI=1.03-1.79, I2=0%, fixed model) and renal carcinoma (OR=4.86, 95% CI=2.72-8.67, I2=0%, fixed model).However, no significant association between CD117 and DFS was found in overall studies. Conclusions: CD117 expression might be a predictive factor of poor prognosis in some surgically treated cancers, particularly in renal carcinoma.     

Differences in the vascular patterns of basal and squamous cell skin carcinomas explain their differences in clinical behaviour

Tumour angiogenesis is essential for tumour growth and appears to play an important role both at the transition from hyperplasia to invasive growth and at a late stage in the dissemination process. Basal cell carcinomas (BCCs) and trichoepitheliomas (TEs) are related tumours that share the properties of invasive growth but without the capacity to metastasize. Squamous cell carcinomas (SCCs) of the skin are derived from a similar cell type and they have both invasive and metastatic potential. The aim of this study was to investigate whether the behaviour of these tumours could be explained by differences in their microvasculature. The study looked both qualitatively and quantitatively at the microvasculature of BCCs (n=50) and TEs (n=33) and compared them with normal skin (n=6) and with SCCs of the skin (n=22). Vessel counts were performed using a standard graticule count method after immunohistochemical staining for CD31. Counts were made of blood vessels in the stroma surrounding the tumour and also for vessels in the body of the tumour. The stromal counts for all the tumour groups differed significantly from normal skin. The SCC counts differed significantly from the counts for the BCCs and TEs. There was no significant difference between the counts for different subtypes of BCC or TE groups. While vessels could be found in the body of the SCCs, none was seen in the nodular BCC or the TE groups. There was no correlation between the vascular density and the depth of invasion. Overall, invasive growth correlated with an angiogenic response in the stroma, while metastatic potential correlated with microvessels being present in the body of the tumour.