GLUT-1 staining of squamous cell carcinomas of the uterine cervix identifies a novel element of invasion (original) (raw)
Related papers
2004
Hypoxia inducible factor-1␣ (HIF-1␣) has been proposed as a candidate endogenous marker of tumor hypoxia and as a molecular mediator of hypoxia-driven malignant progression and acquired treatment resistance. In this study, HIF-1␣ expression in 68 biopsies of oxygenation measurement tracks from squamous cell carcinomas of the uterine cervix of 38 patients was assessed. Expression of HIF-1␣ was commonly found to increase as a function of distance from microvessels, at the center of tumor cell aggregations, and in the vicinity of necrotic areas. However, there was no correlation of HIF-1␣ expression with median oxygen tension (oxygen partial pressure; pO 2) and hypoxic fractions (hypoxic fraction < 2.5 mm Hg, hypoxic fraction < 5 mm Hg). The results indicate that HIF-1␣ should not be used as an endogenous marker of tumor hypoxia in locally advanced squamous cell carcinomas of the uterine cervix. Additionally, no significant prognostic impact of HIF-1␣ expression was found in this group of patients.
Cancer Research, 2004
Hypoxia inducible factor-1␣ (HIF-1␣) has been proposed as a candidate endogenous marker of tumor hypoxia and as a molecular mediator of hypoxia-driven malignant progression and acquired treatment resistance. In this study, HIF-1␣ expression in 68 biopsies of oxygenation measurement tracks from squamous cell carcinomas of the uterine cervix of 38 patients was assessed. Expression of HIF-1␣ was commonly found to increase as a function of distance from microvessels, at the center of tumor cell aggregations, and in the vicinity of necrotic areas. However, there was no correlation of HIF-1␣ expression with median oxygen tension (oxygen partial pressure; pO 2) and hypoxic fractions (hypoxic fraction < 2.5 mm Hg, hypoxic fraction < 5 mm Hg). The results indicate that HIF-1␣ should not be used as an endogenous marker of tumor hypoxia in locally advanced squamous cell carcinomas of the uterine cervix. Additionally, no significant prognostic impact of HIF-1␣ expression was found in this group of patients.
THE ASSESSMENT OF THE ANGIOGENESIS IN THE UTERINE CERVIX CARCINOGENESIS
The uterine carcinoma represents one of the most frequent malignant tumors in female. Great progresses were made in the understanding of the mechanisms of the appearance and evolution of the tumors, and also in the early diagnosis of them. In the present time, the discussions are centered on the angiogenesis and the neovascularisation. During the researches regarding the new factors of prognosis in cervical carcinomas, we are interesting firstly in the study of neoangiogenesis and its predictive role. The microanatomic quantitative study was made on fragments which were processed from uterine cervix dysplasias, preinvasive and invasive tumors. The sections were stained specific immunohistochemically (CD34) and examined with an interactive digital program. We have quantified the density of the microvessels/mm2 tumor stroma and the density of the microvessels/mm2 tumor. The preliminary results regarding the study of the microvessels in uterine cervix carcinomas show a positive correlation between the density and the evolution of the tumor, the angiogenetic process rises simultaneously with the risk of metastasis. This study shows a significant correlation between the density of vessels and the evolution of the uterine cervix carcinomas, the appearance of recurrences and metastasis. The quantification of the angiogenesis is an indicator with an high degree of precision, with is used for the detection of the aggressiveness and malignancy of the uterine cervix tumors.
Interrelationship of proliferation and hypoxia in carcinoma of the cervix
International Journal of Radiation Oncology*Biology*Physics, 2000
Purpose: In human cervix cancer treated with radiotherapy, we have previously shown from separate groups of patients that tumor hypoxia and proliferation rate as measured by bromodeoxyuridne (BrdU) labeling index (LI) are important determinants of clinical outcome. We now examine the relationship of these two pre-treatment predictive assays in 43 patients studied prospectively from 1994 -98 where both tests were performed for each patient. Material and Methods: Newly diagnosed patients with carcinoma of the cervix were examined under anesthesia for staging purposes. Patients were given BrdU (200 mg) by intravenous route prior to the procedure. Tumor oxygenation was measured with the Eppendorf pO 2 histograph. Biopsy of tumor was then performed and the BrdU LI was obtained by flow cytometry. The degree of tumor hypoxia for each tumor was expressed as median pO 2 values, and as the percentage of pO 2 readings <5 mmHg (HP 5 ). Results: The median age was 53 years (range 23-79 years). There were 32 squamous, and 11 non-squamous carcinomas. FIGO stages were: IB and IIA, 8; IIB, 17; IIIB, 18; with a median tumor size of 6 cm (range 2-10 cm). The patients received uniform treatment with radical radiation therapy. There were 22 diploid and 21 aneuploid tumors. The median LI, pO 2 , and HP 5 were 8.0%, 5.4 mmHg, and 46.8%, respectively. Tests for linear associations showed no significant correlation between median pO 2 vs. LI (r ؍ 0.078, p ؍ 0.62), and HP 5 vs. LI (r ؍ ؊0.14, p ؍ 0.38). Conclusions: The clinical outcome in this group of patients is immature, but these results suggest that tumor hypoxia and proliferation measurements are independent and potentially complementary predictive assays in cervix carcinoma. Further investigations are required to examine the distribution of proliferating tumor cells and its relationship with hypoxic tumor cells in tissue sections with the use of immunohistological techniques and image analysis systems.
Strahlentherapie und Onkologie, 2006
Background: Tumor hypoxia is considered to be relevant for several aspects of tumor pathophysiology, for acquired treatment resistance, and tumor progression (e.g., in cancers of the uterine cervix). Therefore, there is a demand for simple and universally applicable methods allowing the estimation of oxygenation status in patient material obtained during pretherapeutic diagnostic procedures (biopsies) or surgical treatment. Protein members of the transcriptional response to hypoxia expressed in tumor tissue, e.g., hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1) and carbonic anhydrase IX (CA IX) are currently being discussed as "endogenous hypoxia markers". Material and Methods: The (hypothetic) suitability of different markers for the assessment of the oxygenation status is reviewed on the basis of current knowledge. Results: Data from studies investigating the suitability of different markers are conflicting. Although a robust induction of HIF-1α, GLUT-1 and CA IX by hypoxia has been demonstrated in vitro, this reaction is modulated both by confounding factors of the tumor microenvironment and intrinsic traits of malignant cells in vivo. Conclusion: On the basis of the available data, the suitability of "endogenous hypoxia markers" for the estimation of the oxygenation status of advanced cervix cancers seems questionable.
Lacking hypoxia-mediated downregulation of E-cadherin in cancers of the uterine cervix
British journal of cancer, 2013
Experimental studies have established a causal connection between tumour hypoxia, hypoxia-associated proteome changes and downregulation of E-cadherin, the final common pathway of epithelial-to-mesenchymal transition (EMT). Our study aimed at elucidating the interrelationship of these processes in cancers of the uterine cervix in vivo. Tumour oxygenation was assessed in 48 squamous cell carcinomas (SCC) of the uterine cervix using polarographic needle electrodes. The expression pattern of E-cadherin was investigated by immunohistochemistry and western blotting, and was compared with that of the hypoxia-inducible proteins glucose transporter (GLUT)-1 and carbonic anhydrase (CA) IX in biopsy specimens of the oxygenation measurement tracks. The majority of cervical cancers (52%) were E-cadherin positive, with a complete absence of the antigen in only 10% of the tumours. No correlation was found between the level of E-cadherin expression and the oxygenation status (mean pO(2), median pO...
BMC cancer, 2014
Tumour microenvironment is a fundamental aspect of tumour behaviour, modulating important events as cancer cell migration and invasion, as well as angiogenesis and metastisation. Among other microenvironment features, hypoxia and acidity play important roles in this modulation. As the metabolic reprogramming of cancer cells induces extracellular acidity, which in turn induces angiogenesis, and hypoxia induces both the metabolic reprogramming and angiogenesis, the present study aims to evaluate the immunohistochemical expression of a variety of metabolic and vascular markers as common targets of the hypoxic microenvironment in a series of cervical squamous cells carcinoma, as well as using an in vitro 3D culture model. Immunohistochemical expression of MCT1, MCT4, CD147, GLUT1 and CAIX was assessed in a series of 28 chronic cervicitis, 34 LSIL, 29 HSIL, 38 cases of squamous cells carcinoma (SCC), as well as in in vitro 3D culture of keratinocytes expressing HPV genes. Furthermore, VE...
2020
High Grade Serous Ovarian Cancer (HGSOC) is one of the deadliest gynecological diseases in the United States ranking fifth in cancer deaths among women. Approximately 22 thousand new cases are expected to occur in the year 2020, and unfortunately, it is estimated that 14 thousand women will succumb to the disease; the incidence to death ratio, 64%, remains high despite current research. Current treatment includes debulking surgery followed by combinatorial chemotherapeutics with platinum-based and taxol-based compounds. But despite aggressive surgery and standard-of-care chemotherapeutics, 80% of patients will experience a recurrence and only 15-30% of those with recurring disease will respond to further treatment. Tumors consist of a heterogeneous population of cell types. A small minority of tumor cells, called cancer stem cells (CSCs), can self-renew and differentiate and are thought to be responsible for recurrent, chemoresistant disease. A cancer cell's ability to migrate and invade other tissues is a hallmark of metastatic disease. To invade, cells must undergo a process called an epithelial-mesenchymal transition (EMT) in which epithelial genes such as CDH1, which codes for E-Cadherin (E-CAD), a cell-cell adhesion molecule, are repressed by the transcription factor SNAI1 (Snail) and genes associated with a mesenchymal phenotype, such as CDH2, which codes for N-Cadherin (N-CAD) are upregulated. This switch from epithelial to mesenchymal gene expression leads vi ACKNOWLEDGEMENTS I would like to extend my gratitude to Dr. Juli Unternaehrer who, so graciously, allowed me to perform this research in her lab as well as provide me continual guidance and support throughout this process. A special thank you to Evgeny Chirshev from Dr. Unternaehrer's lab whose hard work and dedication contributed to my thesis. In addition, I would like to thank the other members of Dr. Unternaehrer's lab, Antonella Bertucci, Nozomi Hojo, Alyse Hill & Hanmin Wang, who were always available for guidance and support. Furthermore, to Dr. Nicole Bournias-Vardiabasis and Dr. Daniel Nickerson, thank you for taking the time to serve on my thesis committee. I would also like to thank CIRM Bridges program,
Histopathogenesis of carcinoma in situ of the uterine cervix
Bulletin of the World Health Organization, 1962
Cancer of the cervix is amenable to treatment provided it is diagnosed at the preinvasive stage, and it is therefore imperative to be able to identify cases of symptomless cervical cancer, which invariably presents no visible alteration in the appearance of the mucous membrane. Fortunately, this is possible by study of vaginal smears for exfoliated cells.In view of the ease with which carcinoma of the uterine cervix can be induced in mice and of its similarity to analogous lesions in women, it was thought that study of early cytological and morphological changes in cervical carcinoma of the mouse-especially at the in situ stage-might prove valuable for biological and therapeutic studies of human cervical carcinoma.This paper reports on study of the progressive epithelial changes in the mouse cervix by means of exfoliated cells in vaginal smears and histological examination of the cervical epithelium after intravaginal painting with 3,4-benzpyrene. The authors consider that basal cel...