Myometrial Responses to Beta-Adrenoceptor Antagonists in Gynecological Malignancies.

OBJECTIVE: The aim of the study was to determine the influence of beta-adrenoceptor (ADRB) antagonists on contractile activity of the nonpregnant human uterus in patients affected by gynecological malignancies. DESIGN: This was a controlled and prospective ex vivo study. SETTING: The work was conducted as a collaboration between 4 academic departments. MATERIALS AND METHODS: Myometrial specimens were obtained from women undergoing hysterectomy for benign gynecological disorders (reference group; N = 15), and ovarian (N = 15), endometrial (N = 15), synchronous ovarian-endometrial (N = 3), and cervical cancer (N = 10). Contractions of myometrial strips in an organ bath before and after applications of ADRB antagonists (propranolol, bupranolol, SR 59230A, and butoxamine) were studied under isometric conditions. RESULTS: Propranolol and bupranolol attenuated contractions in the endometrial and cervical cancer groups similar to that in the reference group (all p < 0.05), whereas opposite effects were observed in the ovarian and synchronous ovarian-endometrial cancer groups. SR 59230A and butoxamine significantly increased contractions in the ovarian cancer group (both p < 0.001). LIMITATIONS: These results require now to be placed into a firm clinical context. CONCLUSIONS: Our study indicates that ovarian cancer considerably alters contractile activity of the nonpregnant human uterus in response to ADRB antagonists. This suggests a pathogenetic role of beta-adrenergic pathways in this malignancy. Furthermore, propranolol and bupranolol substantially influence spontaneous uterine contractility.

Analysis of mutations of PARP1, RNF213, PAX8, KMT2C, MTRR in malignant mesothelioma of testicular tunica vaginalis testis.

Molecular next gene sequencing was used to evaluate mutations in 409 common mutated cancer-related genes in malignant mesothelioma of tunica vaginalis testis (MMTVT) of 81-year-old man. Multifocal papillary-solid areas contained necrosis among highly cellular fields with multiple mitoses. It was positive for WT1, CKAE1/AE3, calretinin, CK7 with negativity for CK5, PSA, TTF-1. Following mutations were revealed in PARP1 (NM_001618: c.2285TG, p.K135R), MTRR (NM_024010: c.147A>G, p.I49M) and two sorts of mutations in structure of KMT2C gene (NM_170606: c.2447_2448insA (c.2447dupA), p.Y816fs and NM_170606: c.1042G>A, p.D348N) for the first time in MMTVT.

Review on significance of GDNF, PTCH1 and RNF213 in chromophobe renal cell carcinoma illustrated by the case of 71-years-old man.

Here we review the role of GDNF, PTCH1, RNF213 illustrated by a case of renal cell carcinoma, chromophobe type (pT2a 8th pTNM edition) of the left kidney of 71-year-old man. Status of potential hotspots in 409 tumor genes were studied by means of next generation sequencing (NGS) technology (IonTorrent - Thermo Fisher Scientific, USA) using Ion AmpliSeq™ Comprehensive Cancer Panel. Next-generation sequencing (NGS) revealed mutations of GDNF (NM_001190468: c. 328C>T, p.R110W, allelic frequency 46%), PTCH1 (NM_001083607:c. 2969C

Heritage of Stanislaw Ciechanowski (1869-1945)-Discoverer of pathogenesis of prostatic hyperplasia-passionis insignia signis fulgent mirificis .

BACKGROUND: Prostatic enlargement was first correctly recognized as a prostatic hyperplasia by professor of anatomic pathology, Stanislaw Ciechanowski (1869-1945) in Cracow on contrary to Parisian urologist Jean Casimir Félix Guyon's concepts of progressing atherosclerosis as a morphological cause of prostatic overgrowth and mechanical insufficiency of lower urinary tract. METHODS: Primary resources were analyzed about Stanislaw Ciechanowski mainly from depositories of the Section of Special Collection, Stanislaw Konopka Main Medical Library Warsaw and Polish bibliograhy of Estreichers at Jagiellonian University. RESULTS: Professor of anatomic pathology, Stanislaw Ciechanowski (1869-1945) was the first to state that chronic inflammation induced overgrowth of parenchymatous and stromal prostate components in course of benign prostatic hyperplasia. Ciechanowski preformed also pioneer and notable studies in the mechanisms of carcinogenesis and classification of cancer in Poland. As one of the major Polish medical editors and a father of Polish modern medical language he was also very prolific author in the field of congenital pathology, sclerosis of pulmonary arteries, endemic goiter, intestinal emphysema, etc. Due to magnitude of autopsies, he preformed, Stanislaw Ciechanowski was a perfect candidate to complete the first edition of several volumes of main Polish handbook on anatomy of a human body after tragic death of professor Adam Bochenek. CONCLUSIONS: Ciechanowski gained such a high authority, that his opinion was found crucial in prewar Poland in the field of medical publications, but his world-famous achievement was scientific explanation of prostate overgrowth as inflammation induced hyperplasia.

Comparison of E-cadherin with STAT3 and apoptosis regulators: Bak and Bcl-xL in endometrioid adenocarcinomas of different ER-alpha immunoprofile.

E-cadherin is a factor of good prognosis in endometrioid adenocarcinomas, while STAT3 is an oncogenic driver of carcinogenesis. E-cadherin, Bak, Bcl-xL and STAT3 were immunohistochemically detected in 78 human endometrioid adenocarcinomas. E-cadherin correlated with STAT3 (p <. 001, r = 0.537) as well as Bak (p = .005, r = 0.314) and Bcl-xL (p = .002, r = 0.340) in the whole study group. In G2 tumors, E-cadherin associated with Bak (p = .021, r = 0.319), Bcl-xL (p = .026, r = 0.309) and STAT3 (p <.001, r = 0.513) but not in G3 adenocarcinomas. E-cadherin correlated with Bak and Bcl-xL in both G1- and estrogen receptor (ER)-negative tumors with significant relation of E-cadherin and STAT3 in G1- and ER-negative tumors. Antigrowth synergy of expression was preserved for antiapoptotic Bak and proliferation-suppressing E-cadherin in IA adenocarcinomas (p = .031, r = 0.342) with no significance between Bak and E-cadherin or STAT3 and emerging correlation between E-cadherin and Bcl-xL in IB + II tumors instead (p = .003, r = 0.472). E-cadherin correlated with Bak and Bcl-xL in ER-positive adenocarcinomas (p = .002, r = 0.382 and p <.001, r = 0.439, respectively) but not in ER-negative tumors. In conclusion, expression deregulation of studied proteins is reflected in selective loss of correlation between suppressors of tumor growth (E-cadherin and Bak) presumably due to progressing impairment of growth-inhibitory properties of clone of neoplastic cells within higher staging and poorer differentiation.

Structural arrangement of vesicouterine fistula revisited: An immunohistochemical study documenting the presence of the endometrium.

Previous research has described a woman of reproductive age who presented with a vesicouterine fistula (VUF) of 20 months' duration. The VUF was lined with a metaplastic glandular epithelium containing both estrogen receptors (ER) and progesterone receptors (PR) in abundance. The aim of the present investigation was to evaluate the histology of the VUF canal when exposure to urine of the cellular elements within the fistula was of much shorter duration. A 41-year-old woman who developed a VUF during her third cesarean section was treated with transvesical fistula excision, electrocoagulation, and subsequent attempted hormonal treatment. Later, the patient underwent open surgery fistula repair. Postoperative specimens were subjected to anatomopathological examination together with immunohistochemical staining for ER and PR using monoclonal anti-human antibodies. Herein, we present for the first time detailed microscopic evidence that, at two separate timepoints, the fistulous tract was lined with the endometrium, which covered approximately 80% of the length of the VUF canal. In its intermediate segment, the urothelium formed an additional layer on the surface of the endometrium. At both timepoints, in the columnar epithelial and stromal endometrial cells lining the fistula, both ER and PR were present in abundance. In conclusion, VUF in subjects of reproductive age fulfill criteria for endometriosis. This study provides a rationale for the conservative treatment of VUF consistent with the hormonal treatment of endometriosis.

Review on Retinal Gliosis Illustrated with a Series of Massive Glioses and Focal Nodular Gliosis Cases in Regard to Potential Pitfalls of Ocular Reactive Tumor-like Lesions of this Type.

This paper presents a review on retinal gliosis illustrated by series of three cases of patients (a 39-year-old man and a 35-year-old woman with massive retinal gliosis (MRG) and a 51-year-old man with truly focal nodular gliosis of retina) with intraocular tumor-like masses and loss of vision, who recently suffered from painful inflammation of eyeball and who classically had a history of remote ocular trauma, onset of blindness early in lifetime or gradual but progressive loss of sight. The diagnosis of this pathological entity is given for the lesions that are composed of GFAP strongly positive, elongated, fusiform cells consistent with fibrillary astrocytes. As illustrated in cases from our pathological practice, PAS gave positive patchy disseminated reaction in form of cellular densely purplish granules in minority of cells representing glycogen storing. This feature could be consistent with PAS-positive Müller cells that also constitute retinal gliosis as one of cellular components of normal retina that is induced to reactive proliferation. Thus, the paper presents histological background and differential diagnosis of the entity.

Malignant gastrointestinal neuroectodermal tumor (clear cell sarcoma-like tumor of the gastrointestinal tract) of the small intestine in a 12-year-old boy.

The aim of this paper is a clinical and anatomopathological demonstration of a malignant lesion, a gastrointestinal neuroectodermal tumor (GNET), as an exceedingly rare cause of ileus in the pediatric population. Specifically, we present the case of a 12-year-old boy who showed dramatic weight loss, hypochromic anemia, fever, dehydration, exaggerated granulation of the terminal ileum, and mechanical ileus due to the obstruction by an intramural tumor of the small intestine. A 50cm-long part of the small intestine with pathological stricture was surgically removed, sampled and routinely fixed and stained with hematoxylin and eosin. The additional immunostains that were preformed were: PAS, S-100, HMB-45, NSE, LCA, CK AE1 / AE3, desmin, SMA, vimentin, CD99, NSE, synaptophysin, WT-1, calretinin, and DOG-1. Moreover, fluorescent in situ hybridization (FISH) with the EWSR1 Break Apart FISH Probe was applied. The neoplasm was composed of nests and alveolar patterns of frankly malignant clear cells with immunoreactivity to S-100, vimentin, and CD 99. The FISH technique detected chromosomal breaking at 22q12. The tumor metastasized to both the mesenteric lymph nodes and a number of hepatic segments. With several chemotherapy protocols, repeat laparotomies, and liver thermal ablations, the patient had a 1.5-year-long survival from the moment of diagnosis. The diagnosis of this malignancy requires both histopathological evaluation and molecular analysis, and the follow-up is based on careful clinical imaging of the neoplastic spread in order to apply proper surgical and oncological treatments. In conclusion, the clinical course of GNET was highly aggressive.

Professional interest in dermatopathology of Stanislaw Ostrowski - the only one State Polish President among physicians.

President of prewar Lvov and Polish Republic on Exile, associate professor Stanislaw Ostrowski was a dermatologist with a keen interest in dermatopathology. This study was based on original resources, which - mainly reports of his own authorship - were focused on dermatopathology. Stanislaw Ostrowski provided excellent description of naevus epitheliomatosus sebaceus Wolters-Friboes both in Polish and German to be cited after decades in renowned handbooks of dermatopahtology published by Springer Verlag. His scientific output also includes meticulous presentation of Fox-Fordyce disease (apocrine miliaria) as well as gold-induced skin changes to Polish readership. Thus, this study documents dermatopahtological achievements of Stanislaw Ostrowski - the unifying statesman of society of Lvov and Polish emigration in London.

Review of prognostic and predictive aspects of mutated TP53 in Wilms' tumor biology with morphological report and molecular analysis of 37-year-old man's nephroblastoma.

Here we review prognostic and predictive aspects of mutated TP53 in Wilms' tumor biology on the basis of the morphological report and molecular analysis of adult nephroblastoma (diffuse blastemal pattern) of a 37-year-old man. Among quite different proteins, TP53 affects expression of several genes such as hypoxia inducible proteins GLUT1 and EPO as well as multidrug resistance (MDR) mediated by P-glycoprotein (Pgp/MDR1) and multidrug-resistant related protein (MRP1), with certain clinical implications. TP53 mutation was found both in our primary tumor (c.746G>T p.R249M frequency 92%) and in nodal metastasis (c.746G>T p.R249M frequency 90%), and the common polymorphism p.P72R in the same gene was revealed with frequency of about 97% in both primary tumor and metastatic disease with appliance of NGS technology (IonTorrent - LifeTechnology) using Ion AmpliSeq Cancer Hotspot Panel v2.

Eventual proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and Cx26 can depend on ER-alpha overexpression in human endometrioid adenocarcinoma.

Estrogen receptor (ER) and progesterone receptor (PgR) accumulations lead to impairment of gap junctional intercellular communication in endometrial cancer. The task of this study was to explore relationships of Cx26 and Cx43 with anti-apoptotic protein Bcl-xL and proapoptotic agent Bak in ER-alpha and PgR negative or variably positive endometrioid adenocarcinomas. Cx26, Cx43, Bak, Bcl-xL, PgR and ER-alpha were detected in 78 endometrioid adenocarcinomas with immunohistochemistry. There was a remarkable cellular re-distribution of Cx26 and Cx43 from normally membranous location in normal endometrium to aberrantly cytoplasmic expression in endometrioid adenocarcinomas, thus suggesting the decrease of functional membranous gap junctions in the malignancy. Bak failed to correlate with Cx43 regardless of either PgR or ER-alpha status of tumors, while Bcl-xL positively correlated with Cx43 in ER-alpha positive tumors (p = 0.001, r = 0.427) and both PgR positive (p = 0.019, r = 0.312) and negative (p = 0.015, r = 0.509) cancers. Similarly, Bcl-xL significantly associated with Cx26 in ER-alpha positive tumors (p = 0.036, r = 0.267) and both PgR positive (p = 0.026, r = 0.297) and negative (p = 0.046, r = 0.429) cancers. On the contrary, Bak exclusively correlated with Cx26 only in ER-alpha negative tumors (p = 0.027, r = 0.551). ER-alpha status of endometrioid adenocarcinomas could restrict eventual proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and Cx26 in these tumors.

Vulvar angiomyofibroblastoma--a case report of rare entity mimicking Bartholin cyst.

Vulvar angiomyofibroblastoma is rare tumor of obscure histological origin. Here a case of 49-year old woman is described with this intriguing benign vulvar entity. The tumor developed at left vulvar labia and clinically imitated Bartholin cyst with clinical complaints of regional discomfort without pain. A macroscopic evaluation revealed well separated, encapsulated tumor of 3,5 cm in diameter. On cut surface the tumor was whitish, flesh, solid with myxoid appearance without any apparent cysts formation. There were alternating hypo- and hypercellular in the neoplasm. Microscopically the tumor comprised proliferation of small thin walled vessels that were surrounded with cuffs and islands of epithelioid, spindle and plasmacytoid cells with occasional vacuolization. Some aggregations of cells were quite dense and in such fields, vessels were compressed and ecstatic enough to mimic a bit haemangiopericytoma pattern. A production of myxoid intercellular matrix was seen in loose, hypocellular areas and was confirmed by positive pas-alcian blue stain that demonstrated prominent myxoid stroma and intracytoplasmatic globules of acid glicoproteins. The immunoprofile was remarkable enough to show strong expression of vimentin and desmin, while there was a lack of pan-keratin (CKAE1/3) and smooth muscle actin (SMA) immunoreactivities. Such an immunofentype is regarded to share some of myofibrolastic origin despite SMA negativity. Tumor cells seemed to sprout from perivascular regions giving an impression of accumulations strictly associated with neighbouring vascular branches. This configuration of cells is very often viewed as pericyte-like proliferation. Thus, our case of angiomyofibroblastoma is an example of tumor that probably derives from perivascular stem cells that acquire some of myoid features.

Allergic diseases: the price of civilisational progress.

Atopic disorders are a major global health problem. The prevalence of asthma, allergic rhinitis and atopic dermatitis has been increasing over the last four decades, both in the industrialized and developing countries. It seems to be related to changes in the social structure, increasing industrialization, pollution and dietary changes. Many hypotheses link the allergy epidemic to stringent hygiene, dominance of a westernized lifestyle and an accelerated pace of life. Dietary antioxidants, lipids, sodium, vitamin D seem also to be implicated. We endeavour to review the most relevant theories with a special emphasis on the hygiene, antioxidative, lipid and air pollution hypotheses. It is however important to note that none of them explains all the aspects of unprecedented rise in the prevalence of allergic disorders. A complex interplay between host's immune response, invading pathogens, diversity of environmental factors and genetic background seems to be of a particular importance. Current allergy epidemic is multifactorial and basic and epidemiologic studies are warranted to further our understanding of this phenomenon.

[Bilateral metastases of renal cell carcinoma to the ovaries--a case report]. / Obustronne przerzuty raka jasnokomórkowego nerki do jajników--opis przypadku.

Renal cell carcinoma accounts for 75% of renal neoplasms. Clear cell carcinoma is diagnosed in about 80% of the cases. Renal cell carcinoma most frequently metastasizes to the lungs (50-60%), lymph nodes (36%), bones (30-40%), liver (30-40%), and brain (5%). In other organs the metastasis changes are observed very rarely. Ovarian metastases are found in 0.5% of renal cancers. So far, only 23 cases of renal cell carcinoma metastases to the ovary have been reported in the literature. In 18 cases they were metastases of renal cell carcinoma of the clear cell type. The authors present a case of a 50-year-old woman with double-sided metastatic changes to the ovary from renal cell carcinoma. The patient was admitted to the Gynecological ward with preliminary diagnosis of ovarian tumors. Gynecological examination revealed double-sided ovarian tumors, 6-7cm in diameter. Computed tomography also showed a 155 x 80 mm hetrogenous, multiform tumor localized above the uterus. In addition, CT showed a 75 x 55 mm tumor in the lower pole, and a smaller one, 15 mm in diameter in the upper pole of the right kidney. Laboratory tests were normal. The antigen Ca 125 was 25 j/ml. Mammography cytology gastroscopy colonoscopy were normal. The consulting urologist proposed a two-stage treatment. In the first stage, the removal of the double-sided ovarian tumors was proposed, while in the second stage the right nephrectomy was suggested. Double-sided ovarian tumors were found and removed (in the wall of the cyst- yellow, solid masses) during the first operation. Intraoperative histological examination showed changes with unknown grade of malignancy in both ovaries (number of studies QN 291). The patient underwent total hysterectomy. On day 5 postoperatively the woman was discharged from the hospital in good condition with the recommendation to pick up the histological test result in two weeks time. The final histological examination showed metastatic changes of renal cell carcinoma of the clear cell type (number of studies QN569-582, QN 585-608). The diagnosis of bilateral renal cell carcinoma metastases to the ovaries was confirmed by immunohistochemical studies using antibodies CD 10 and Vimentin (number of studies CT 1558-1559). The patient was directed to the Urological Ward. The surgery confirmed the presence of the tumor in the lower pole (about 8 cm in size), and a smaller one (about 1 cm in size) in the upper pole of the right kidney. The right nephrectomy was performed. Histological examination confirmed the primary clear cell renal cell carcinoma. The patient was directed to the next oncological treatment.

Spontaneous rupture of unscarred uterus in the early second trimester: a case report of placenta percreta.

BACKGROUND: Prevalence of uterine rupture at delivery has been recently estimated at less than 1 in 2500 deliveries. Spontaneous uterine rupture in the early mid-trimester (16 weeks gestation or less), is far less frequent. We report a case of uterine rupture due to placenta percreta in otherwise uncomplicated pregnancy CASE: A 35-year-old, gravida 5, para 5, at 15wk 2d gestation (menstrual age) with negative history of uterine scarring suddenly developed symptoms of incipient hypovolemic shock while being hospitalized for imminent miscarriage. On exploratory laparotomy we found a midline uterine rupture infiltrated by the placenta. Supracervical hysterectomy was performed. Postoperative lab analysis confirmed the elevated serum AFP levels. CONCLUSION: Abnormal placentation and subsequent uterine rupture should be taken into consideration also in women in the second trimester who have no history of uterine instrumentation.

STAT3 and apoptosis regulators: Bak and Bcl-xL in endometrioid adenocarcinomas of different estrogen receptor-α immunoprofile.

Estrogen receptor (ER) is a major feature of endometrioid adenocarcinoma. It has a significant impact on constitution of estrogen-responsiveness of this endometrial malignancy, in which STAT3 (signal transducer and activator of transcription) becomes hyperactivated. The aim of our study was to detect immunohistochemically and compare expressions of STAT3 with apoptosis regulators (Bak and Bcl-xL) in regard to different pathological features and variably pronounced ER-α immunoprofile in 78 endometrioid adenocarcinomas. STAT3 was abundantly detected in nuclei of cancer cells in 54 cases, thus pointing at its activation as an universal nuclear transcriptional factor. Bcl-xL and Bak were expressed in cytoplasm of malignant cells in 62 and 20 cancers, respectively. STAT3 correlated both with Bcl-xL (p = 0.001, r = 0.365) and Bak (p  < 0.001, r = 0.436) in all of endometrioid adenocarcinomas and variably in different subgroups of these tumours segregated in regard to grading, staging and patients' age. Remarkably, only ER-α positive cancers retained these correlations in opposition to ER-α negative tumours with negativity defined as an immunoreactivity below 10%. ER-α receptor probably enhances interactions between STAT3 and Bcl-xL to be present in statistically significant manner. Presence of ER-α receptor seems to be crucial for relationships among Bcl-xL and STAT3 to occur in endometrioid adenocarcinomas.

[Gap junction intercellular communication in carcinogenesis of endometrial cancer]. / Komunikacja miedzykomórkowa z udzialem polaczen typu gap w karcinogenezie blony sluzowej trzonu macicy.

One of the mechanisms for direct cell to cell signaling is mediated by gap junctions. These junctions are formed by connexins, transmembrane proteins. Gap junction intercellular communication (GJIC) plays a critical role in tissue development, differentiation of cells, and regulation of tissue homeostasis. Cancer cells are characterized by growth and/or differentiation disorders. Endometrial cancer is the most common gynecological malignancy in developed countries. In this study we discuss the putative role of GJIC and adhesion molecules in the development of endometrial cancer The relationships of GJIC to the process of apoptosis and function of some adhesion proteins have also been underlined.

Imbalance in Coagulation/Fibrinolysis Inhibitors Resulting in Extravascular Thrombin Generation in Gliomas of Varying Levels of Malignancy.

Neoplastic processes are integrally related to disturbances in the mechanisms regulating hemostatic processes. Brain tumors, including gliomas, are neoplasms associated with a significantly increased risk of thromboembolic complications, affecting 20-30% of patients. As gliomas proliferate, they cause damage to the brain tissue and vascular structures, which leads to the release of procoagulant factors into the systemic circulation, and hence systemic activation of the blood coagulation system. Hypercoagulability in cancer patients may be, at least in part, a result of the inadequate activity of coagulation inhibitors. The aim of the study was to evaluate the expression of the inhibitors of the coagulation and fibrinolysis systems (tissue factor pathway inhibitor, TFPI; tissue factor pathway inhibitor-2 TFPI-2; protein C, PC; protein S, PS, thrombomodulin, TM; plasminogen activators inhibitor, PAI-1) in gliomas of varying degrees of malignancy. Immunohistochemical studies were performed on 40 gliomas, namely on 13 lower-grade (G2) gliomas (8 astrocytomas, 5 oligodendrogliomas) and 27 high-grade gliomas (G3-12 anaplastic astrocytomas, 4 anaplastic oligodendrogliomas; G4-11 glioblastomas). A strong expression of TFPI-2, PS, TM, PAI-1 was observed in lower-grade gliomas, while an intensive color immunohistochemical (IHC) reaction for the presence of TFPI antigens was detected in higher-grade gliomas. The presence of PC antigens was found in all gliomas. Prothrombin fragment 1+2 was observed in lower- and higher-grade gliomas reflecting local activation of blood coagulation. Differences in the expression of coagulation/fibrinolysis inhibitors in the tissues of gliomas with varying degrees of malignancy may be indicative of their altered role in gliomas, going beyond that of their functions in the hemostatic system.

Heterogeneous Expression of Proangiogenic and Coagulation Proteins in Gliomas of Different Histopathological Grade.

Brain gliomas are characterized by remarkably intense invasive growth and the ability to create new blood vessels. Angiogenesis is a key process in the progression of these tumors. Coagulation and fibrinolysis factors play a role in promoting angiogenesis. The aim of the study was to evaluate the expression of proangiogenic proteins (VEGF and bFGF) and hemostatic proteins (TF, fibrinogen, fibrin, D-dimers) associated with neoplastic cells and vascular endothelial cells in brain gliomas of various degrees of malignancy. Immunohistochemical tests were performed using the ABC method with the use of mono- and polyclonal antibodies. The obtained results indicated that both neoplastic cells and vascular endothelial cells in gliomas of various degrees of malignancy are characterized by heterogeneous expression of proteins of the hemostatic system and angiogenesis markers. The strongest expression of proangiogenic factors and procoagulant factors was demonstrated in gliomas of higher-grade malignancy.

Relationships between hypoxia markers and the leptin system, estrogen receptors in human primary and metastatic breast cancer: effects of preoperative chemotherapy.

BACKGROUND: Tumor hypoxia is marked by enhanced expression of hypoxia-inducible factor-alpha (HIF-1alpha) and glucose transporter-1 (Glut-1). Hypoxic conditions have also been associated with overexpression of angiogenic factors, such as leptin. The aim of our study was to analyze the relationships between hypoxia markers HIF-1alpha, Glut-1, leptin, leptin receptor (ObR) and other breast cancer biomarkers in primary and metastatic breast cancer in patients treated or untreated with preoperative chemotherapy. METHODS: The expression of different biomarkers was examined by immunohistochemistry in 116 primary breast cancers and 65 lymph node metastases. Forty five of these samples were obtained form patients who received preoperative chemotherapy and 71 from untreated patients. RESULTS: In primary tumors without preoperative chemotherapy, HIF-1alpha and Glut-1 were positively correlated (p = 0.02, r = 0.437). HIF-1alpha in primary and metastatic tumors without preoperative therapy positively correlated with leptin (p < 0.0001, r = 0.532; p = 0.013, r = 0.533, respectively) and ObR (p = 0.002, r = 0.319; p = 0.083, r = 0.387, respectively). Hypoxia markers HIF-1alpha and Glut-1 were negatively associated with estrogen receptor alpha (ERalpha) and positively correlated with estrogen receptor beta (ERbeta). In this group of tumors, a positive correlation between Glut-1 and proliferation marker Ki-67 (p = 0.017, r = 0.433) was noted. The associations between HIF-1alpha and Glut-1, HIF-1alpha and leptin, HIF-1alpha and ERalpha as well as Glut-1 and ERbeta were lost following preoperative chemotherapy. CONCLUSIONS: Intratumoral hypoxia in breast cancer is marked by coordinated expression of such markers as HIF-1alpha, Glut-1, leptin and ObR. The relationships among these proteins can be altered by preoperative chemotherapy.