Phosphorylated KDR expression in endometrial cancer cells relates to HIF1alpha/VEGF pathway and unfavourable prognosis.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor for many malignant neoplasms exerting its function through activation of specific membrane receptors, that is, KDR/flk-1, residing in endothelial cells. Several recent reports indicate that VEGF receptors are also expressed in cancer cells, suggesting that specific VEGF-originated cancer cell reactions may parallel the endothelial response. Using a novel monoclonal antibody, recognizing the activated (phosphorylated) form of the KDR receptor (pKDR), we assessed the expression of pKDR in normal and malignant endometrium. A strong and consistent cytoplasmic and nuclear pKDR expression was noted in the normally cycling endometrium, including epithelial, stromal and endothelial cells, suggesting a role in the normal menstrual cycle. Approximately, one-third of the 70 stage I endometrioid adenocarcinomas analysed exhibited an intense cytoplasmic and nuclear pKDR expression in both cancer cells and peritumoral vessels. It was noted that such pKDR reactivity in cancer cells was related directly to VEGF, VEGF/KDR complexes and HIF1alpha (hypoxia inducible factor 1alpha) expression. Furthermore, pKDR expression was significantly associated with poor prognosis. It is concluded that the VEGF/KDR pathway is activated in both normally cycling and malignant endometrium, suggestive of an important role in the biology of this tissue. The unfavourable prognosis that VEGF confers to endometrial adenocarcinomas could be attributed to its angiogenic activity, but also to a direct effect on cancer cells through an autocrine VEGF/KDR loop.     

Increased expression of hypoxia-inducible factor 1alpha in type I and type II endometrial carcinomas.

Hypoxia-inducible factor 1alpha (HIF-1alpha) is a nuclear protein that is upregulated in many tumors and triggers biologic events intimately associated with aggressive tumor behavior. The aim of this study was to analyze the expression of HIF-1alpha, vascular endothelial growth factor (VEGF), Ki-67 and p53 in type I and type II endometrial adenocarcinoma. In total, 149 patients diagnosed with endometrial adenocarcinoma in our institute from 1995 to 2001 were included in this study, of which 108 were type I and 41 were type II endometrial adenocarcinoma. Patient demographics, clinical and pathological data were reviewed. Tissue microarrays were prepared from the paraffin blocks and immunohistochemistry was performed for antibodies against HIF-1alpha, VEGF, Ki-67 and p53. High expression of HIF-1alpha, VEGF, Ki-67 and p53 were significantly more frequent in type II than type I endometrial adenocarcinoma (P<0.001). HIF-1alpha expression was highly correlated with VEGF expression in the tumor cells (P=0.001). In type I endometrial adenocarcinoma, high expression of HIF-1alpha showed a significant correlation with higher grade of the tumor, depth of myometrial invasion, adnexal invasion and clinical stage. A similar correlation was not observed in type II endometrial adenocarcinoma. Surgical stage was the only independent prognostic marker for survival. In conclusion, high expression of HIF-1alpha is more frequent in type II than in type I endometrial adenocarcinoma. In type I endometrial adenocarcinoma, HIF-1alpha expression correlates with morphologic features of aggressiveness. In type II endometrial adenocarcinoma, there is no correlation between HIF-1alpha expression and these features. Thus, HIF-1alpha may play an important role in endometrial adenocarcinoma progression, particularly in type I endometrial adenocarcinoma. Additional investigations of HIF-1alpha as a biomarker of aggressive potential and as a novel target for therapeutics in endometrial adenocarcinoma are warranted.     

Thymidine phosphorylase expression in normal and hyperplastic endometrium

AIMS: To investigate the expression of thymidine phosphorylase (TP), a known angiogenic factor for endothelial cells, in normally cycling endometrium and various forms of endometrial hyperplasia. METHODS: TP expression was assessed with the P-GF.44C monoclonal antibody, using the alkaline phosphatase anti-alkaline phosphatase method. Ninety two normal and hyperplastic endometria were studied. RESULTS: In normal proliferative endometrium, TP is found exclusively in the basal layer and the inner third of the functionalis; expression is cytoplasmic in glandular epithelium and nuclear in stromal cells. It is invariably patchy. This immunohistochemical picture remains almost unaltered during the early and mid secretory phase of the normal menstrual cycle but, most impressively, TP is expressed uniformly in the epithelium of all endometrial glands towards the end of the cycle. At this stage, expression is mixed nuclear/cytoplasmic and there is very little stromal nuclear staining. In simple endometrial hyperplasia, the staining pattern for TP is identical to normal proliferative endometrium, with a distribution that is usually limited to a few rather weakly proliferating glands and to the adjacent periglandular stroma of the deep endometrium. The distribution is more extensive in complex and atypical endometrial hyperplasias, where a mixed nuclear/cytoplasmic pattern usually prevails over the pure cytoplasmic reaction. CONCLUSIONS: TP is expressed consistently in normal and hyperplastic endometrium, suggesting a role in physiological and pathological angiogenesis. In normal endometrium, TP has a definite pattern of distribution, which is dependent on the phase of the menstrual cycle, whereas in all forms of endometrial hyperplasia the enzyme is randomly distributed and lacks an orderly pattern.     

Differential expression of Yes-associated protein is correlated with expression of cell cycle markers and pathologic TNM staging in non-small-cell lung carcinoma

Yes-associated protein, a downstream effector of the Hippo signaling pathway, has been linked to progression of non-small-cell lung carcinoma. The aim of this study was to investigate expression of Yes-associated protein in lung adenocarcinoma and squamous cell carcinoma. Associations of Yes-associated protein expression with clinicopathologic parameters, expression of cell cycle-specific markers, and epidermal growth factor receptor gene amplification were also analyzed. In a univariate analysis of the 66 adenocarcinomas, high nuclear expression of Yes-associated protein was significantly correlated with expression of cyclin A and mitogen-activated protein kinase. Multivariate analysis, including age and sex, showed that cyclin A expression was independently correlated with nuclear expression of Yes-associated protein in adenocarcinomas. Furthermore, high nuclear expression of Yes-associated protein was also a significant predictor of epidermal growth factor receptor gene amplification for adenocarcinoma. For the 102 squamous cell carcinomas, univariate analysis revealed that high cytoplasmic expression of Yes-associated protein was correlated with the low pathologic TNM staging (stage I) and histologic grading. Multivariate analysis, including age and sex, showed that cytoplasmic expression of Yes-associated protein was an independent predictor of low pathologic TNM staging. These results indicate that nuclear overexpression of Yes-associated protein contributes to pulmonary adenocarcinoma growth and that high cytoplasmic expression of Yes-associated protein is an independent predictor of low pathologic TNM staging and histologic grading. The differential effects of Yes-associated protein expression patterns in adenocarcinomas and squamous cell carcinomas suggest that Yes-associated protein may play important roles in different pathways in distinct tumor subtypes. These observations may, therefore, lead to new perspectives on therapeutic targeting of these tumor types.     

Immunohistochemical detection of hepatocyte nuclear factor 1beta in ovarian and endometrial clear-cell adenocarcinomas and nonneoplastic endometrium

Recent studies have noted specific expression of hepatocyte nuclear factor (HNF) 1beta in ovarian clear-cell adenocarcinoma (CCA). In this study, we aimed to determine whether HNF-1beta can be a specific marker of CCA in both the ovary and the endometrium and to assess the pathological significance of HNF-1beta expression in CCAs. We examined HNF-1beta expression immunohistochemically in 186 ovarian carcinomas, including 40 CCAs; 33 endometrial carcinomas, including 5 CCAs; 22 endometria at different stages of the menstrual cycle (5 in the proliferative, 12 in the secretory, and 5 in the menstrual phases); and 7 gestational endometria. The incidence of HNF-1beta immunoreactivity differed significantly between CCAs and other histology in both the ovary (100% in the former versus 2% in the latter) and the endometrium (100% in the former versus 0% in the latter) (P < .0001 each). In nonneoplastic endometrium, 25% or more immunoreactive cells were confined to the mid-to-late secretory phase of the menstrual cycle and gestational endometrium. HNF-1beta would be an excellent marker for distinguishing CCAs from other lesions in both the ovary and the endometrium. HNF-1beta expression seems to be associated with physiopathological cytoplasmic glycogen accumulation in these organs.     

β-catenin、Glut-1和PTEN蛋白在子宫内膜样腺癌发生过程中的表达及意义

目的 通过分析子宫内膜上皮内瘤变(EIN)诊断、分类与子宫内膜增生WHO(2003)分类的关系,探讨β-catenin、Glut-1和PTEN蛋白在子宫内膜样腺癌发生过程中的表达及其意义.方法 根据EIN诊断及分类标准,对83例子宫内膜增生病例进行再分类.采用免疫组织化学SP法,对10例增殖期子宫内膜、83例子宫内膜增生及24例子宫内膜样腺癌组织中β-catenin、Glut-1及PTEN蛋白的表达进行检测.结果 (1)83例子宫内膜增生病例中共检出24例EIN病例,总检出率为28.9%(24/83).24例EIN病例中,来自复杂型不典型性增生16例(66.7%,16/24),但EIN的检出率与不典型增生的分级无明显关系(P＞0.05).(2)β-catenin蛋白在增殖期子宫内膜中呈正常表达,良性子宫内膜增生的异常表达率为10.2%(6/59),而EIN和子宫内膜样腺癌的异常表达率(50%,12/24;66.7%,16/24)分别明显高于良性子宫内膜增生(P＜0.01),但二者间的异常表达率差异无统计学意义(P＞0.05).(3)Glut-1蛋白在增殖期子宫内膜、良性子宫内膜增生组织中均呈低表达,而在EIN和子宫内膜样腺癌中的高表达率分别为58.3%(14/24)和70.8%(17/24),均显著高于增殖期子宫内膜及良性子宫内膜增生(P＜0.01),但二者高表达率间差异无统计学意义(P＞0.05).(4)PTEN蛋白在EIN病例中的失表达率(37.5%,9/24)与子宫内膜样腺癌(62.5%,15/24)、增殖期子宫内膜(2/10)及良性子宫内膜增生(28.8%,17/59)比较差异均无统计学意义(P＞0.05),但子宫内膜样腺癌的失表达率则明显高于增殖期子宫内膜及良性子宫内膜增生病例,其差异均具有统计学意义(P＜0.05).结论 β-catenin蛋白的异常表达和Glut-1蛋白高表达是子宫内膜样腺癌发生过程中的早期事件,二者在区别良性子宫内膜增生、EIN和子宫内膜样腺癌中可能是有用的免疫标志物.PTEN蛋白失表达是子宫内膜样腺癌发生过程中的极早期事件,但将其作为EIN病变的诊断性标志物并不恰当.     

窖蛋白-1在肺癌中的表达及意义

目的 探讨窖蛋白-1（caveolin-1）在不同类型肺癌组织中的表达及其与微血管密度（MVD）和临床病理因素之间的关系。方法 对154例原发性肺癌、相应癌旁正常肺组织及36例淋巴结转移癌行caveolin-1免疫组织化学染色;对154例原发性肺癌行CD34免疫组织化学（SP法）染色并进行微血管密度计数;Western印迹法检测其中50例新鲜肺癌组织及其癌旁正常肺组织中caveolin-1的表达情况。结果 caveolin-1为膜／质表达蛋白,在正常支气管上皮细胞和肺泡上皮细胞中的阳性率为100％。在肺癌组织中的阳性率为59．1％（91／154）,低于癌旁正常肺组织,P＜0．01;Western印迹结果进一步证实caveolin-1在肺鳞癌、肺腺癌组织中的表达均显著低于癌旁正常肺组织,P＜0．01。caveolin-1在小细胞肺癌（SCLC）和非小细胞肺癌（NSCLC）中的阳性率分别为7．1％和64．3％,二者间差异有统计学意义,P＜0．01。NSCLC中,有淋巴结转移组caveolin-1表达高于无淋巴结转移组（P=0．005）;Ⅲ、Ⅳ期组caveolin-1表达显著高于Ⅰ、Ⅱ期组（P=0．042）,caveolin-1表达与NSCLC的其他临床病理因素及MVD值无关（P＞0．05）。结论caveolin-1其作为一种肿瘤抑制因子的同时,可能还具有促进NSCLC进展和转移的活性。     

Expression and prognostic value of FOXP1 in esophageal squamous cell carcinoma

BackgroundForkhead box protein P1 (FOXP1) has been suggested as a prognostic marker in several malignant tumors. However, the significance of FOXP1 in esophageal squamous cell carcinoma (ESCC) is still unclear. The purpose of this study was to investigate the expression pattern of FOXP1 in normal esophageal tissue and ESCC and to analyze the clinicopathological significance and prognostic value of FOXP1 in ESCC.MethodsFOXP1 was detected by immunohistochemistry using tissue microarrays containing tumor tissues and adjacent normal tissues from 270 ESCC patients with oncological follow-up data.ResultsNormal esophageal tissues predominantly showed an exclusive nuclear FOXP1 (n-FOXP1) expression pattern, and no exclusive cytoplasmic FOXP1 (c-FOXP1) staining was found. In ESCC, the expression rates of exclusive n-FOXP1-positive, exclusive c-FOXP1-positive, both nuclear and cytoplasmic positive and complete negative were 14.4%, 28.9%, 10.4% and 46.3%, respectively. High n-FOXP1 expression was significantly correlated with decreased postoperative recurrence and distant metastasis (P < 0.05). Furthermore, elevated c-FOXP1 expression was significantly associated with regional lymph node metastasis and distant metastasis (P < 0.05). High c-FOXP1 expression had an effect on shorter overall survival (OS) time, but the difference was not statistically significant (P > 0.05). Kaplan–Meier analysis showed that ESCC patients with high n-FOXP1 expression survived significantly longer than patients with low n-FOXP1 expression. Multivariate analysis confirmed that patients with high n-FOXP1 staining exhibit good prognosis and n-FOXP1 was an independent factor for ESCC prognosis.ConclusionsOur results suggest that FOXP1 plays an essential role in ESCC progression and prognosis and may be a useful biomarker for predicting survival.     

Forkhead box protein P1 is a useful marker for the diagnosis of mucinous minimal deviation adenocarcinoma of uterine cervix

Mucinous minimal deviation adenocarcinoma (MDA) is a rare highly differentiated tumor of uterine cervix, of which the confusing histopathology resembling some benign lesions usually makes difficulty for pathologic diagnosis. The expression of forkhead box protein P1 (FOXP1) is found in some kinds of human tumors and is considered to be associated with the progression of the tumors. The purpose of this study is to detect the FOXP1 expression in MDA and evaluate its possible role in the diagnosis of MDA. Twenty-two MDA cases and 20 control cases consisting of 10 cases of lobular endocervical glandular hyperplasia and 10 cases of normal endocervical tissue were included in this study. All available clinical data were collected and immunostaining for FOXP1, carcinoembryonic antigen (CEA), human milk fat globule antigen 1 (HMFG1), estrogen receptor, and progesterone receptor were performed on these cases. The nuclear/cytoplasmic expression of FOXP1 was found in 18 of 22 MDA cases while in 1 of 20 control cases, which showed statistical significance (P = .000). The cytoplasmic CEA expression was found in 14 of 22 MDA cases and 2 of 20 control cases (P = .000), whereas cytoplasmic HMFG1 expression was found in 10 of 22 MDA cases and 4 of 20 control cases (P = .081). No statistical difference was found between FOXP1 and CEA expression (P = .083) or between FOXP1 and HMFG1 expression (P = .375) in MDA. Neither estrogen receptor nor PR expression was found in MDA. The significant expression of FOXP1 in MDA may be helpful to some extent in the pathologic diagnosis of cervical MDA. A widened observation range and further researches are needed to elucidate the potential mechanism.     

Nuclear, compared with combined nuclear and cytoplasmic expression of maspin, is linked in lung adenocarcinoma to reduced VEGF-A levels and in Stage I, improved survival

Aims:  To evaluate whether there is a correlation between the subcellular localization of maspin and the histological, molecular and biological features of pulmonary adenocarcinoma, particularly addressing the hypothesis that the tumour inhibitor properties of maspin may be linked to a nuclear, compared with a combined nuclear and cytoplasmic expression pattern.
Methods and results:  The subcellular expression of maspin was determined in 80 resected pulmonary adenocarcinomas (Stage I, 46; Stage II, 10; Stage III, 20; Stage IV, 4) and correlated with histological grade, proliferative rate, p53 expression, vascular endothelial growth factor (VEGF)-A levels, and prognosis (mean follow-up of 41.5 months). Cases with nuclear (N) maspin ( n  = 47), compared with the [N + cytoplasmic (C)] group ( n  = 28), showed lower ( P  ≤ 0.05): histological grade, proliferative rate, p53 expression and VEGF-A levels. Cox multivariate analysis revealed in stage I adenocarcinomas (N) maspin as the only predictor of improved survival.
Conclusions:  (N) maspin selects lung adenocarcinomas with distinct molecular and clinical features, supporting the hypothesis that its tumour inhibitor properties may be linked to its nuclear localization.     

Correlation between infiltration of FOXP3 regulatory T cells and expression of B7-H1 in the tumor tissues of gastric cancer

Background

Substantial evidence suggests that the expansion of regulatory T cells (T_regs) plays a pivotal role in immunological evasion of tumors. Recent studies have demonstrated that a majority of tumor cells overexpress B7-H1, and this overexpression is associated with poor disease prognosis. Although an increase of T_regs and B7-H1 has been revealed in several malignancies, their correlation in gastric cancer has not been studied.

Methods

Tumor sections from 111 gastric cancer patients were stained for FOXP3 and B7-H1 by immunohistochemistry. The expression levels of these two molecules were statistically associated with various factors involved in disease progression and prognosis. The correlation between their expression levels was analyzed.

Results

The infiltration of FOXP3⁺ Tregs and expression of B7-H1 were observed in gastric cancer tissues, and there was a highly significant correlation between these two molecules (P < 0.01). The expression of FOXP3⁺ Tregs and B7-H1 was associated with lymph node metastasis and the clinicopathological stage and prognosis of gastric cancer patients. The expression levels of these two determinants in patients with lymph node metastasis and an advanced clinicopathological stage were distinctly higher (P < 0.05). The patients with enhanced expression of FOXP3⁺ Tregs and B7-H1 exhibited a lower overall survival rate and a worse prognosis (P < 0.05).

Conclusions

Increased expression of FOXP3⁺ Tregs and B7-H1 was observed in gastric cancer tissues; the two molecules were closely correlated with each other, suggesting that they might be used as new biomarkers to predict the disease progression and prognosis. Combinatorial immunotherapeutic approaches based on depleting the T_regs and blocking B7-H1 might improve therapeutic efficacy in gastric cancer.     

Beta-catenin expression as a prognostic indicator in cervical adenocarcinoma

The purpose of this study was to assess the prognostic influence of beta-catenin expression by immunohistochemistry in patients with cervical adenocarcinomas. The study group comprised of 51 patients who underwent total hysterectomy for cervical cancer. The median follow-up was 39 months (range 1-138 months). beta-catenin was expressed strongly on the membranes of normal cervical epithelial and glandular cells. Uniform membranous beta-catenin staining localized to intercellular borders was observed in 35% of tumors, whereas 65% of tumors demonstrated an abnormal pattern of reduced or aberrant beta-catenin expression (i.e., cytoplasmic and/or nuclear staining patterns). Abnormal beta-catenin immunoreactivity was associated statistically with advanced pathologic stage (p=0.018). The 10-year disease-free survival was 51.0% in patients with preserved expression of beta-catenin. On the other hand, a poorer prognosis was noted in the group with abnormal expression of beta-catenin with a 10-year disease-free survival of 43.4%. By multivariate analysis, low pathologic stage (stages I and II, p=0.001) and preservation of beta-catenin expression (p=0.012) were independently favorable prognostic factors. Our results indicate that changes in beta-catenin expression occur during the progression of cervical adenocarcinoma to an invasive phenotype. These results suggest that beta-catenin is an important intercellular adhesion molecule. Assessment of beta-catenin immunoreactivity may be a useful prognostic tool in cervical adenocarcinoma complementary to established prognostic factors. Furthermore, we developed a strategy for choosing biomarkers representing the steps in malignant progression in an effort to identify patients with occult metastases who will need adjuvant therapy and spare women from unnecessary interventions.     

Breast cancer risk in usual ductal hyperplasia is defined by estrogen receptor-alpha and Ki-67 expression

The hypothetical multistep model for breast carcinogenesis indicates that invasive carcinoma arises via a series of intermediate hyperplastic lesions through various grades of atypia to in situ and invasive carcinoma. Non-atypical hyperplasia [hyperplasia of usual type (HUT)] is a nonobligate precursor of breast cancer. Although its further morphological subclassification is unlikely, refining is more likely to depend on defining biological markers of risk. Having assembled a cohort of benign proliferative breast lesions of known outcome, we studied the expression of estrogen receptor-alpha (ER-alpha) and Ki-67 using morphometric image analysis as well as dual-labeled immunofluorescence in HUT foci and in surrounding normal lobules of 25 patients that progressed to breast cancer and 19 controls. Those patients that progressed to breast cancer (cases) showed significantly higher ER-alpha [median, 57.00% of cells within individual HUT foci; interquartile range (IQ), 33.48 to 67.78] and Ki-67 (median, 3.82%; IQ, 0.85 to 11.28) expression in their HUT foci compared with controls (ER-alpha median, 30.27%; IQ, 19.75 to 52.50 and Ki-67 median, 0.77%; IQ, 0.0458 to 1.72, P = 0.008 and <0.001). No significant difference in expression of dual-stained cells was found between cases and controls. Although normal lobules from cases showed higher ER-alpha expression compared with controls, this was not statistically significant. Our data point to a previously undescribed hormone-dependent pathway in this particular group of breast neoplasms and suggest the possibility of selective hormonal therapy to suppress the proliferative potential of these benign but high-risk breast lesions. The findings of this study might have important implications for improving breast cancer screening and management strategies.     

Increased expression of human macrophage metalloelastase (MMP-12) is associated with the invasion of endometrial adenocarcinoma

To evaluate the association between the expression of human macrophage metalloelastase (matrix metalloproteinase-12, MMP-12) with cancer invasion and differentiation of endometrial adenocarcinoma, specimens from endometrial adenocarcinoma (n=61) of diverse stages and histologic types were collected from patients having undergone hysterectomy, and specimens from normal endometrium (n=38) were obtained from patients with benign diseases. The expression of MMP-12 was analyzed immunohistochemically, by Western blot, and RT-PCR. The positive rate of MMP-12 was significantly increased in endometrial adenocarcinoma (81.97%) as compared with that in normal endometrium (13.16%). The results showed that expression of MMP-12 correlated with stage (p=0.022) and grade (p=0.018) of endometrial cancer. MMP-12 immunoreactive proteins were found mainly on the glandular epithelial cells of endometrial adenocarcinoma. The macrophage infiltration detected by CD68 immunohistochemical staining in endometrial adenocarcinoma was also higher than that in normal endometrium. In this study, we show that in addition to macrophages, endometrial adenocarcinoma cells are able to express MMP-12. Increased MMP-12 expression tended to be associated with the extent of adenocarcinoma invasion accompanied by marked macrophage infiltration. Our results suggest that MMP-12 is an important oncogene in high-stage and high-grade endometrial adenocarcinoma.     

Increased expression of the adult stem cell marker Musashi-1 in endometriosis and endometrial carcinoma

Adult stem cells are thought to be responsible for the high regenerative capacity of the human endometrium, and have been implicated in the pathology of endometriosis and endometrial carcinoma. The RNA-binding protein Musashi-1 is associated with maintenance and asymmetric cell division of neural and epithelial progenitor cells. We investigated expression and localization of Musashi-1 in endometrial, endometriotic and endometrial carcinoma tissue specimens of 46 patients. qPCR revealed significantly increased Musashi-1 mRNA expression in the endometrium compared to the myometrium. Musashi-1 protein expression presented as nuclear or cytoplasmic immunohistochemical staining of single cells in endometrial glands, and of single cells and cell groups in the endometrial stroma. Immunofluorescence microscopy revealed colocalization of Musashi-1 with its molecular target Notch-1 and telomerase. In proliferative endometrium, the proportion of Musashi-1-positive cells in the basalis layer was significantly increased 1.5-fold in the stroma, and three-fold in endometrial glands compared to the functionalis. The number of Musashi-1 expressing cell groups was significantly increased (four-fold) in proliferative compared to secretory endometrium. Musashi-1 expressing stromal cell and cell group numbers were significantly increased (five-fold) in both endometriotic and endometrial carcinoma tissue compared to secretory endometrium. A weak to moderate, diffuse cytoplasmic glandular staining was observed in 50% of the endometriosis cases and in 75% of the endometrioid carcinomas compared to complete absence in normal endometrial samples. Our results emphasize the role of Musashi-1-expressing endometrial progenitor cells in proliferating endometrium, endometriosis and endometrioid uterine carcinoma, and support the concept of a stem cell origin of endometriosis and endometrial carcinoma.     

The expression profile of RNA-binding proteins in primary and metastatic colorectal cancer: relationship of heterogeneous nuclear ribonucleoproteins with prognosis

The heterogeneous nuclear ribonucleoproteins are a group of RNA-binding proteins with a range of key cellular functions, which are dysregulated in tumorigenesis including regulation of translational and RNA processing. The aims of this study were to define the heterogeneous nuclear ribonucleoprotein expression profile in primary and metastatic colorectal cancer and to establish the clinicopathologic significance of this expression. A tissue microarray containing 515 primary colorectal cancers, 224 lymph node metastasis of colorectal cancer, and 50 normal colon samples was immunostained for 6 heterogeneous nuclear ribonucleoproteins. Heterogeneous nuclear ribonucleoprotein I, heterogeneous nuclear ribonucleoprotein K, and heterogeneous nuclear ribonucleoprotein L displayed the most frequent strong immunoreactivity in primary colorectal tumor samples. Heterogeneous nuclear ribonucleoprotein A1 (P < .001) and heterogeneous nuclear ribonucleoprotein U (P = .003) showed significant alterations in nuclear expression in tumors compared with normal colonic epithelium, whereas heterogeneous nuclear ribonucleoprotein A1 (P = .001), heterogeneous nuclear ribonucleoprotein I (P < .001), and heterogeneous nuclear ribonucleoprotein K (P < .001) all showed significant aberrant cytoplasmic immunoreactivity in tumor cells. There were also significant differences in cytoplasmic immunoreactivity between the primary tumor and the corresponding lymph node metastasis for heterogeneous nuclear ribonucleoprotein A1 (P = .001), heterogeneous nuclear ribonucleoprotein I (P < .001), and heterogeneous nuclear ribonucleoprotein K (P = .001). Nuclear heterogeneous nuclear ribonucleoprotein H (χ(2) = 72.1; P < .001), cytoplasmic heterogeneous nuclear ribonucleoprotein I (χ(2) = 28.1; P < .001), and cytoplasmic heterogeneous nuclear ribonucleoprotein K (χ(2) = 13.2; P = .04) all showed significant associations with tumor stage. There was a significant relationship between strong nuclear heterogeneous nuclear ribonucleoprotein H expression and survival (χ(2) = 14.97; P < .001). This study has defined the expression profile of heterogeneous nuclear ribonucleoproteins in colorectal cancer and shown that there are significant alterations in both expression and subcellular localization of individual heterogeneous nuclear ribonucleoproteins in this type of tumor.     

子宫内膜样腺癌组织中PRRX1蛋白的表达及临床意义

目的探讨配对相关同源框1(paired related homoeobox 1,PRRX1)蛋白在子宫内膜样腺癌组织中的表达及临床意义。方法选取安徽医科大学第一附属医院以及安徽医科大学附属巢湖医院267例子宫内膜组织标本,其中正常子宫内膜86例,子宫内膜上皮内瘤变90例,子宫内膜样腺癌91例,均行免疫组化EliVision法检测,观察不同子宫内膜组织中PRRX1表达及子宫内膜样腺癌临床病理特征与PRRX1的关系。结果PRRX1蛋白表达主要定位于子宫内膜样腺癌组织的细胞核中,91例子宫内膜样腺癌组织中PRRX1阳性率为79.1%,高于正常子宫内膜组织(0)、子宫内膜上皮内瘤变组织(10.0%),差异有统计学意义(P<0.05)。子宫内膜样腺癌患者按FIGO分级分类,FIGO1级的PRRX1阳性率低于FIGO 2、3级,差异有统计学意义(P<0.05);按患者年龄、临床分期、有无淋巴结转移分组,PRRX1阳性率差异均无统计学意义(P>0.05)。结论子宫内膜样腺癌组织中的PRRX1表达量高,且与FIGO分级相关。