pax8 positive ovarian cancer

This study aims to study the effect of PAX8 induced by ADSCs on ovarian cancer's growth and invasion through stabilizing TAZ. 1 OC includes epithelial, germ cell and sex cord-stromal tumors originating from surface epithelial cells, from the germ cell or the oocyte and from stromal and primitive ovarian sex cord cells, as shown in Figure 1. In cancer, PAX8 expression is deregulated in a key set of neoplasms, including those arising . Although the traditional model of carcinogenesis has focused on the ovary as a tumor initiation site, recent studies suggest that there may be additional sites of origin outside the ovary, namely the secretory cells of the fallopian tube. Cases that did not fit this criteria were considered negative. PAX8 antibody is expressed in a high percentage of renal cell carcinomas and ovarian cancers. In the present study, we evaluated if, in addition to the routine morphologic diagnosis, the biomarker PAX8 could be useful in recognition of ovarian epithelial cancer cells prior to the neoadjuvant chemotherapy.METHODS:Two hundred and two cytology specimens including 120 pretreatment ovarian cancer samples, 60 benign controls, and 22 malignant . Formalin-fixed paraffin-embedded tissue samples from 71 patients of unfavorable subsets of unknown primary . WT1 expression was positive in 61 (71%) cases, mainly expressed in serous carcinoma, regardless of their differentiation degree, and negative in 24 (27%) cases. Among the 68 effusion specimens with metastatic ovarian carcinoma, immunostaining showed positive results for PAX8 in 58 cases (85%) and positive results for WT1 in 56 cases (82%; Table 1) Image 1. PAX8 was evaluated for nuclear staining only. The association between epithelial cancers and paired-box gene 8 (PAX8) has been studied significantly before. Nearly all ovarian carcinomas express PAX8, and its knockdown results in apoptosis of ovarian cancer cells. First, PAX8 positively regulates mutated p53, and missense p53 mutations have an oncogenic gain of function effect. References Tacha D, Zhou D, Using the prediction analysis of microarrays (PAM) method, the expression of 61 genes was analyzed in 68 breast and 57 ovarian carcinoma samples and PAX8 expression was found at higher levels in ovarian compared with breast cancer ( 26 ). secretory epithelia or PEG cells stain positive for PAX8, 600. In the Mllerian system, PAX8 is expressed in a variety of ovarian tumors, particularly serous carcinoma. Elucidating the function of PAX8 on the pathology of stomach cancer was meaningful. It was found that PAX8 was up-regulated significantly in ovarian cancer cells treated with ADSC, accompanied by the hippo signalling pathway activation. PAX8 was found to be positive in 37 of 41 (90%) ovarian carcinoma cases studied, and was a sensitive (90%) and specific (100%) marker for the detection of metastatic ovarian carcinoma. and cell proliferation (Ki67, green) and nuclei (Hoechst33342, blue); and the percentage of positive cells for those markers (d). A statistically significant difference was noted for the PAX-8 staining and cancer type with P value < 0.001. When combining with Calretinin, PAX8 is a sensitive marker to diagnose the carcinomas of ovarian origin, which will be ideal to be used for those patients with a possible advanced ovarian cancer prior to receiving neoadjuvant chemotherapy. PAX8 immunolocalization in epithelial ovarian cancer tissue (A) and (B) PAX8 immunostaining of healthy thyroid tissue indicating strong nuclear staining in the follicular epithelia, 200 (A) and . Effect of the RET Inhibitor Vandetanib in a Patient With RET Fusion-Positive Metastatic Non-Small-Cell Lung Cancer. In endometrial cancers, 84% (113 of 134) of the cases were positive and in cervical cancer, 98% (1 of 60) squamous cell carcinomas cases were negative and 83% (5 of 6) cervical adenocarcinomas were positive. PAX8 was found to be upregulated in primary stomach cancer tissue and the TCGA stomach cancer dataset. KW - Ovarian cancer. KW - Marker. We present a case of primary peritoneal serous cystadenocarcinoma mimicking advanced colorectal cancer in a 68 yr-old African American female. (A) Lesions of metastatic ovarian cancer from gastric adenocarcinoma, with PAX8 negative staining (magnification, 200). This reflects, in part, a lack of early symptoms and proven ovarian cancer screening tests. (A) Lesions of metastatic ovarian cancer from gastric adenocarcinoma, with PAX8 negative staining (magnification, 200). Familiarity with the full spectrum of the cytomorphologic features of benign Mullerian epithelium, including metaplasia . The positive rate of PAX8 in 20 patients with ovarian benign tumor was 85% (17/20), showing no significant statistical difference in comparison with the PEOC group (P=0.761). Immunoreactivity was graded based on the stainings KW - Neoadjuvant chemotherapy. A PAX8 positive result was taken as the nucleus appearing yellowish-brown or brown. PAX8 is involved in the development of thyroid follicular cells and the expression of thyroid-specific genes (5). PAX8 is a cell lineage-specific transcription factor which plays a crucial role in the organogenesis of the kidney, thyroid gland and Mllerian duct. Malignant surface epithelial tumors Ovarian cancer is the most common cause of gynecologic cancer death. . There are few studies in literature . In all cases of ovarian cancers 79% (181 of 229) expressed PAX8, and in thyroid cancer, PAX8 was expressed in 90% (9 of 10) cases. The DSS values were determined for the two subpopulations, the PAX8-positive HGSOC cells and the PAX8-negative non-cancerous cells, based on the cell viability values for each dose. PAX8 is a common marker for kidney cancer, thyroid cancer and cancers of the female reproductive system. Our study demonstrates that high-grade serous tumors can . The expression of Pax8 (Fig. Stable PAX8 depleted ovarian cancer cells were generated using short hairpin RNA (shRNA) constructs. Based on site of cancer, all endometrium carcinoma showed positive expression of PAX-8 with P value < 0.001. Ovarian cancer (OC) represents the fifth leading cause of cancer-related death in women and, like other cancers, is a spectrum of diseases. The relative distribution of gene alterations in pediatric . Interestingly, SOX13 and PAX8 showed consistent expression patterns, and the . There were only 14 patients who had positive expression of PAX-8; including 11/15 (73.3%) adenocarcinoma and 3/45 (6.7%) SCC. PAX8 as an Immunohistochemical Marker for Mesothelioma PAX8 is considered a negative marker for mesothelioma. The previously reported interaction between PAX8 and ep300 serves as a positive control . The importance of PAX8 in the development of the reproductive system is highlighted by abnormalities observed upon the loss or mutation of this PAX family member. PAX8 expression was positive in 70 (81.39%) cases, the remaining 15 (17.44%) negative cases suggesting a non-Mllerian origin. One case was not valuable due to technical difficulties. PAX8 [BC12] has been designed to target restricted epitopes and exhibits higher specificity and provides sharper staining than the PAX8 rabbit polyclonal antibody. All lanes : Anti-PAX8 antibody [EPR23508-20] (ab239363) at 1/1000 dilution Lane 1 : SK-OV-3 (human ovarian cancer epithelial cell), whole cell lysate Lane 2 : NIH:OVCAR-3 (human ovary adenocarcinoma epithelial cell), whole cell lysate Lysates/proteins at 20 g per lane. KW - Ascitic fluid. PAX8 and Myc and decreased PTEN and RB1 mRNA . Primary peritoneal cystadenocarcinoma is a rare tumor of similar histogenic origin as primary ovarian carcinoma. Ovarian cancer is the fifth cause of cancer-related mortality in women, with an expected 5-year survival rate of only 47%. The patient was discharged 13 days after surgery with no complication. Whether similar mechanisms are involved in ovarian cancer pathogenesis is unknown. In addition, calretinin was found to be useful for identifying mesothelial cells in fluid cytology. Loss of PAX8 in high-grade serous ovarian cancer reduces cell survival despite unique modes of action in the fallopian tube and ovarian surface epithelium. PAX8 is expressed in the majority of renal epithelial neoplasms. 2d) was positive and that of CD10 and ER was negative, which indicate that the tumor has the feature of clear cell carcinoma of the ovary, not renal cell carcinoma nor cholangiocarcinoma. (20) , which showed that PAX8 are constantly expressed in normal or non-neoplastic . Introduction. in focal breast cancer, causing false positive results. Expression of PAX8 is increased in neoplastic renal tissues, Wilms tumors, ovarian cancer and Mllerian carcinomas. We propose that PAX8 be recommended for use in a clinical histopathology laboratory setting. . PAX8 proved to be a specific and a sensitive marker for renal cell carcinoma (90%) and ovarian carcinomas (79%), with serous and endometrioid ovarian carcinomas having 89% sensitivity. Western Blot Analysis Eighteen established renal, ovarian, prostatic, breast, colonic, cervical, and brain tumor cell lines were also used to evaluate PAX8 protein . In all cases of ovarian cancers 79% (181 of 229) expressed PAX8, and in thyroid cancer, PAX8 was expressed in 90% (9 of 10) cases. PAX2 and PAX8 immunohisyochemistries are useful for differentiating numerous primary tumour types from metastatic ones. WT1 expression was positive in 61 (71%) cases, mainly expressed in serous carcinoma, regardless of their differentiation degree, and negative in 24 (27%) cases. PAX8 is a member of the Paired-Box gene family (PAX1-9) of transcription factors whose expression is tightly controlled temporally and spatially. Normal processes of embryonic development and abnormal transformation to cancer have many parallels, and in fact many aberrant cancer cell capabilities are embryonic traits restored in a distorted, unorganized way. Radiology, endoscopy and cytology yielded only inconclusive findings. Second, PAX8 directly transcriptionally regulates p21, in a p53-independent. 2 Mucinous carcinoma of the ovary (MC). Eleven of 22 (50.0%) patients without endometriosis showed positive PAX2 expression, while eight of 36 (22.2%) patients with endometriosis showed positivity ( P = 0.016). were PAX8 positive and h-caldesmon negative. PAX8 occupies an intragenic enhancer in the LYPD1 gene locus for LYPD1-expressing ovarian cancer cell lines OVCAR3, KURAMOCHI, and COV318 but not OVCAR4 (Fig. PAX8 immunolocalization in epithelial ovarian cancer tissue (A) and (B) PAX8 immunostaining of healthy thyroid tissue indicating strong nuclear staining in the follicular epithelia, 200 (A) and 400 (B). PAX8 was not only a mitotic factor, but identified as a transcription factor involved in the prognosis of human tumor patients. . In endometrial cancers, 84% (113 of 134) of the cases were positive and in cervical cancer, 98% (1 of 60) squamous cell carcinomas cases were negative and 83% (5 of 6) cervical adenocarcinomas were positive. 2c) was positive, but the expression CK7 and HNF1 (Fig. When combining with Calretinin, PAX8 is a sensitive marker to diagnose the carcinomas of ovarian origin, which will be ideal to be used for those patients with a possible advanced ovarian cancer prior to receiving neoadjuvant chemotherapy. Immunohistochemical analysis of percutaneously obtained ascitic fluid . High-grade serous ovarian cancer is a deadly disease that can originate from the fallopian tube or the ovarian surface epithelium. PAX8 is positive in most ovarian nonmucinous surface epithelial tumors: serous, clear cell, and endometrioid cell types, especially for endometrioid and clear cell carcinoma, in which WT1 is generally negative or only focally positive [ 6 ]. (an ovarian cancer known to be positive for PAX8 and a mesothelioma known to be positive for Calretinin) and negative (incubation with secondary antibody only) controls were stained in parallel for each round of IHC. PAX8 was considered positive, if moderate or strong staining in more than 5% of tumor cell nuclei were identified [2]. 1 C), suggesting that PAX8 might contribute to the transcriptional regulation of LYPD1 expression. . MBT with focal, mostly weak expression of PAX8 ( f) (200x) Full size image Fig. Ovarian high-grade serous carcinoma (HGSC) is the commonest subtype of human ovarian cancer (), and long-term survival remains poor ().Mutation in TP53 is essentially universal (), whereas germline mutation in BRCA1 or BRCA2 is observed in approximately 15% cases ().These mutations impair the ability to repair DNA double-strand breaks (DSB) via homologous recombination (HR). Background Development of tailored treatment based on immunohistochemical profiles (IPs) of tumors for cancers of unknown primary is needed. Detection of metastatic ovarian carcinoma. Tumors of increasing invasiveness were analyzed and a significant decrease in the scoring of MUC5AC (p=0.001) was observed, with a stronger expression in adenomas (87%) and borderline . PAX8: A sensitive and specific marker to identify cancer cells of ovarian origin for patients prior to neoadjuvant chemotherapy Yue Wang, Yiying Wang, Jie Li, Zeng Yuan, Bingbing Yuan, Tingguo Zhang, Janiel M. Cragun, Beihua Kong, Wenxin Zheng Group enriched (endometrial cancer, ovarian cancer, renal cancer, thyroid cancer) Cancer distribution i . A strong positive correlation was found between PAX8 scoring (p=0.003), CK7 scoring (p=0.0001), and MUC1 scoring (p=0.001) in primary mucinous ovarian cancer. Detailed Description: Tissue will be received from operative specimens ( primary ovarian carcinoma) at time of primary cytoreductive surgery.Ovarian cancer (OC) organoids will be then cultured. Secondary All lanes : Goat Anti-Rabbit IgG, (H+L), Peroxidase conjugated at 1/100000 dilution Samples from pancreatobiliary tract cancer patients were small 3D cluster/CK7+/PAX8- with AUC of 0.8772. . By contrast, PAX8 was stained in none of the breast and almost all ovarian cancer samples, indicating that PAX8 is a more superior marker for the differential diagnosis of ovarian and breast cancer (11). PAX8 staining was present in 99% of high-grade serous ovarian carcinomas and all (100%) low-grade ovarian carcinomas and serous borderline tumors; however, only 74% of these cases (188/254) were diffusely positive in more than 50% of tumors cells, and intensity ranged from strong to weak. (B) Lesions of metastatic ovarian cancer from gastric adenocarcinoma, with PAX8 negative staining (magnification, 400). To explore the role of PAX8 in these tissues, we purified the PAX8 protein complex from nonmalignant fallopian tube cells and high-grade serous ovarian carcinoma cell lines. the secondary aim was to characterize the immunohistochemical features of these cysts to clarifying this issue that, the ovarian cortex microenvironment induces tubal type (pax8 positive) epithelium to these structures and confirm this hypothesis that regardless of the origin of these cysts, progesterone has the ability to suppress this molecular The cell viability was calculated as a percent of cells of each subpopulation after each drug treatment, normalized to the number of cells of the respective . In addition, no significant difference with respect to the positive expression of PAX8 was found among ovarian benign tumors with different pathologies (P=0.533). In 2003, analysis of the PAX8 gene by DNA microarray revealed high expression in ovarian cancer. Introduction KW - Origin. Chromophobe renal cell carcinoma has a lower PAX8 positive rate among the common renal tumour types. Cancer is the second most common culprit of mortality in the United States and epithelial carcinomas are considered as one of the most predominant types of cancer. Abstract. The mortality of lung cancer is high around the world. This means mesothelioma cancer cells usually do not test positive for PAX8. Inset shows 400 magnification. J to L, Pleural malignant mesotheliomas (PLMM) were all negative for PAX8; 23 of 24 pleural malignant mesotheliomas were negative for h-caldesmon. The PAX8 transcription factor is essential for ovarian cancer proliferation, and its silencing in ovarian and endometrial cancer cells leads to apoptosis 1,2. There was a difference in PAX2 and PAX8 expression between in ovarian SMBT with or without endometriosis. Research studies have implicated genetic mutations that result in aberrant expression of PAX genes in a number of cancer subtypes (1-3), with members of subgroups II and III identified as potential mediators of tumor progression (2). Immunoreactivity with normal B lymphocytes was used as an internal positive control and as an intensity reference when present. Paired Box 8 (PAX8) is a lineage-specific transcription factor that has essential roles during embryogenesis and tumorigenesis. Photos 1-8 stained with PAX-8 Table 1: All Cases GO:0045893 [positive regulation of transcription, DNA-templated] PAX8 expression was positive in 70 (81.39%) cases, the remaining 15 (17.44%) negative cases suggesting a non-Mllerian origin. KW - PAX8 Immunostaining showed positivity for both markers in 50 cases (74%) and positivity for either or both markers in 64 cases (94%). Differentiate invasive micropapillary carcinoma of ovarian origin (PAX8+) from other common metastatic invasive micropapillary carcinomas, including those of the bladder, lung, breast, salivary gland and gastrointestinal tract (all PAX8-) ( Am J Surg Pathol 2009;33:1037 ) A PAX8 positive result was taken as the nucleus appearing yellowish-brown or brown. Journal of clinical oncology : official journal of the American . High-grade serous ovarian carcinoma presents significant clinical and therapeutic challenges. Organoids will be validated with a combination of Next Generation Sequencing (NGS) analysis and immunohistochemistry (TP53, PAX8 etc). In (C), a pattern of PAX8 positive intercalating cells is separated by . Product Description. The risk factors like aging and hereditary factors intensify the situation. Because the staining pattern of PAX8 is maintained in serous, endometrioid, and clear cell carcinoma, 12, 13 it is important not to mistake PAX8-positive benign epithelial cells in PWs for PAX8-positive metastatic tumor cells. PAX8 and Calretinin were evaluated for nuclear stain-ing. The PAX (paired box) genes PAX2 and PAX8 are lineage-specific transcription factors required during development of the fallopian tube but not in the development of the ovary. This is mainly attributed to the complete lack of symptoms during the early stages of the disease and absence of an early diagnostic marker.PAX8 is emerging as an important histological marker for most of the epithelial ovarian cancers, as it is expressed in about 90% of malignant ovarian cancers, specifically in HGSC. 2 MATERIALS AND METHODS 2.1 Cell culturing PAX8 mRNA and protein were detected by RT-PCR, immunoblot and immunofluorescence. 14-18 moreover, pax8 is a lineage restricted transcription factor that plays an essential role in the organogenesis of (B) Lesions of metastatic ovarian cancer from gastric adenocarcinoma, with PAX8 negative staining (magnification, 400). PAX8 was positive in 16 cases (32.0%) while negative in 34 cases (68.0%), with 32.0% sensitivity and 100.0% specificity. Cell proliferation, motility and invasion potential of PAX8 silenced cells were analyzed by means of growth curves, wound healing and Matrigel assays. 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