Carcinomas of Distal Fallopian Tube and Their Association with Tubal Intraepithelial Carcinoma: Do They Share a Common “Precursor” Lesion? Loss of Heterozygosity and Immunohistochemical Analysis Using PAX 2, WT-1, and P53 Markers

As the role of distal fallopian tube as organ of serous carcinogenesis is emerging, additional literature on the role of tubal intraepithelial carcinoma (TIC) as a precursor lesion in a subset of primary peritoneal serous carcinomas (PPSC is emerging as well. TIC although fallopian tube in origin can be genetically related to ovarian/peritoneal carcinomas. The role of PAX2 in primary fallopian tube carcinomas (PFTC)/PPSC is yet to be defined. The aim of our study was to understand if the biologic properties of tumors arising in the distal fallopian tube that remain as PFTC are different when they seed on to the peritoneal surface (PPSC). A panel of 6 polymorphic microsatellite markers corresponding to p53, PAX2, and WT1 tumor suppressor genes were studied. Invasive carcinomas as well as TIC arising in the distal fallopian tube when remain as PFTC appears to exhibit different LOH patterns in comparison to PPSC. PAX 2 LOH patterns might represent a “hidden PAX 2 signature” analogous to p53 signatures. PAX 2 might be an emerging marker for detection of early serous carcinomas particularly in BRCA + women.

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STEROID RECEPTOR PHENOTYPE, EXPRESSION OF HER-2/NEU, PD-1, PD-L1 AND LYMPHOCYTIC-MACROPHAGAL INFILTRATION OF ENDOMETRIAL CARCINOMAS: COMPARISON OF MODERN MOLECULAR BIOLOGICAL TYPES OF THE DISEASE (THE ROLE OF BODY MASS INDEX)

Problems in oncology ◽

10.37469/0507-3758-2020-66-1-71-78 ◽

2020 ◽

Vol 66 (1) ◽

pp. 71-78

Author(s):

Lev Bershteyn ◽

Aleksandr Ivantsov ◽

Aglaya Ievleva ◽

A. Venina ◽

I. Berlev

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Tumor Tissue ◽

Immunohistochemical Analysis ◽

The Body ◽

Molecular Profile ◽

Total N ◽

Number Of Patients ◽

Her 2

The aim of this study was to evaluate steroid receptors’ status of tumor tissue in different molecular biological types of endometrial cancer (EC), subdivided according to the current classification, and their colonization by lymphocytic and macrophage cells, taking into account body mass index of the patients. Materials and methods: Material from treatment-naive patients with EC (total n = 229) was included; the number of sick persons varied depending on the method used. The average age of patients was close to 60 years, and about 90% of them were postmenopausal. It was possible to divide the results of the work into two main subgroups: a) depending on the molecular biological type of the tumor (determined on the basis of genetic and immunohistochemical analysis), and b) depending on the value of the body mass index (BMI). The latter approach was used in patients with EC type demonstrating a defective mismatch repair of the incorrectly paired nucleotides (MMR-D) and with a type without characteristic molecular profile signs (WCMP), but was not applied (due to the smaller number of patients) in EC types with a POLE gene mutation or with expression of the oncoprotein p53. According to the data obtained, when comparing various types of EC, the lowest values of Allred ER and PR scores were revealed for POLE-mutant and p53 types, while the “triple-negative” variant of the tumor (ER-, PR-, HER2/neu-) was most common in POLE-mutant (45.5% of cases) and WCMP (19.4%) types of EC. The p53+ type of EC is characterized by inclination to the higher expression of the macrophage marker CD68 and lymphocytic Foxp3, as well as mRNA of PD-1 and SALL4. In addition to the said above, for WCMP type of EC is peculiar, on the contrary, a decrease in the expression of lymphocytic markers CD8 (protein) and PD-L1 (mRNA). When assessing the role of BMI, its value of >30.0 (characteristic for obesity) was combined with an inclination to the increase of HER-2/neu expression in the case of MMR-D EC type and to the decrease of HER-2 /neu, FOXp3 and ER expression in WCMP type. Conclusions: The accumulated information (mainly describing here hormonal sensitivity of the tumor tissue and its lymphocytic-macrophage infiltration) additionally confirms our earlier expressed opinion that the differences between women with EC are determined by both the affiliation of the neoplasm to one or another molecular biological type (subdivided according to the contemporary classification), as well as by body mass value and (very likely) the associated hormonal and metabolic attributes.

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Deleted in malignant brain tumor 1 is secreted in the oviduct and involved in the mechanism of fertilization in equine and porcine species

Reproduction ◽

10.1530/rep-13-0007 ◽

2013 ◽

Vol 146 (2) ◽

pp. 119-133 ◽

Cited By ~ 29

Author(s):

Barbara Ambruosi ◽

Gianluca Accogli ◽

Cécile Douet ◽

Sylvie Canepa ◽

Géraldine Pascal ◽

...

Keyword(s):

Brain Tumor ◽

Western Blot ◽

Immunohistochemical Analysis ◽

Fertilization Rate ◽

Malignant Brain Tumor ◽

Estrus Cycle ◽

Immunofluorescence Analysis ◽

Oviductal Fluid ◽

Porcine Spermatozoa

Oviductal environment affects preparation of gametes for fertilization, fertilization itself, and subsequent embryonic development. The aim of this study was to evaluate the effect of oviductal fluid and the possible involvement of deleted in malignant brain tumor 1 (DMBT1) on IVF in porcine and equine species that represent divergent IVF models. We first performed IVF after pre-incubation of oocytes with or without oviductal fluid supplemented or not with antibodies directed against DMBT1. We showed that oviductal fluid induces an increase in the monospermic fertilization rate and that this effect is canceled by the addition of antibodies, in both porcine and equine species. Moreover, pre-incubation of oocytes with recombinant DMBT1 induces an increase in the monospermic fertilization rate in the pig, confirming an involvement of DMBT1 in the fertilization process. The presence of DMBT1 in the oviduct at different stages of the estrus cycle was shown by western blot and confirmed by immunohistochemical analysis of ampulla and isthmus regions. The presence of DMBT1 in cumulus–oocyte complexes was shown by western blot analysis, and the localization of DMBT1 in the zona pellucida and cytoplasm of equine and porcine oocytes was observed using immunofluorescence analysis and confocal microscopy. Moreover, we showed an interaction between DMBT1 and porcine spermatozoa using surface plasmon resonance studies. Finally, a bioinformatic and phylogenetic analysis allowed us to identify the DMBT1 protein as well as a DMBT1-like protein in several mammals. Our results strongly suggest an important role of DMBT1 in the process of fertilization.

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The Roles of DNA Demethylases in Triple-Negative Breast Cancer

Pharmaceuticals ◽

10.3390/ph14070628 ◽

2021 ◽

Vol 14 (7) ◽

pp. 628

Author(s):

Shoghag Panjarian ◽

Jean-Pierre J. Issa

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Tumor Suppressor Genes ◽

Hormone Receptors ◽

Triple Negative ◽

Breast Cancers ◽

Therapeutic Implications ◽

High Propensity ◽

Dna Methylation Profile

Triple-negative breast cancers (TNBCs) are very heterogenous, molecularly diverse, and are characterized by a high propensity to relapse or metastasize. Clinically, TNBC remains a diagnosis of exclusion by the lack of hormone receptors (Estrogen Receptor (ER) and Progesterone Receptor (PR)) as well as the absence of overexpression and/or amplification of HER2. DNA methylation plays an important role in breast cancer carcinogenesis and TNBCs have a distinct DNA methylation profile characterized by marked hypomethylation and lower gains of methylations compared to all other subtypes. DNA methylation is regulated by the balance of DNA methylases (DNMTs) and DNA demethylases (TETs). Here, we review the roles of TETs as context-dependent tumor-suppressor genes and/or oncogenes in solid tumors, and we discuss the current understandings of the oncogenic role of TET1 and its therapeutic implications in TNBCs.

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The emerging role of the distal Fallopian tube and p53 in pelvic serous carcinogenesis

The Journal of Pathology ◽

10.1002/path.2630 ◽

2010 ◽

Vol 220 (1) ◽

pp. 5-6 ◽

Cited By ~ 22

Author(s):

C Simon Herrington ◽

W Glenn McCluggage

Keyword(s):

Fallopian Tube

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Concurrent Endometrial Intraepithelial Carcinoma (EIC) and Serous Ovarian Cancer: Can EIC Be Seen as the Precursor Lesion?

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e3182434a81 ◽

2012 ◽

Vol 22 (3) ◽

pp. 457-464 ◽

Cited By ~ 16

Author(s):

Thijs Roelofsen ◽

Léon C.L.T. van Kempen ◽

Jeroen A.W.M. van der Laak ◽

Maaike A. van Ham ◽

Johan Bulten ◽

...

Keyword(s):

Ovarian Cancer ◽

Estrogen Receptor ◽

Progesterone Receptor ◽

Expression Patterns ◽

Neoplastic Progression ◽

Precursor Lesion ◽

Ki 67 ◽

Cancer Management ◽

Ploidy Analysis ◽

Intraepithelial Carcinoma

ObjectiveThe pathogenesis of serous ovarian carcinoma (SOC) is still unknown. Recently, endometrial intraepithelial carcinoma (EIC) was proposed to be the precursor lesion of SOC. This study examines the model of EIC as precursor for SOC.MethodsCases of SOC with a noninvasive or superficially invasive serous lesion, a hyperplastic lesion with/without atypia, or EIC in the endometrium were selected for inclusion in this study. Tissue sections from both ovaries, the fallopian tubes, and the uterus were extensively reviewed by an expert gynecopathologist. For both EIC and SOC, immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor; TP53 mutation analysis; and in situ ploidy analysis were performed.ResultsNine cases of SOC with concurrent EIC in the endometrium were identified. Immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor revealed almost identical expression patterns and similar intensities in each pair of EIC and coincident SOC. Identical TP53 mutations were found in SOC and coinciding EIC in 33% of the cases, suggesting a clonal origin. DNA ploidy analysis, as a marker for neoplastic progression, demonstrated an increased number of aneuploid nuclei in SOC compared to their corresponding EIC (P = 0.039). In addition, the mean amount of DNA per nucleus in SOC was higher (ie, more aneuploid) compared to EIC (P = 0.039).ConclusionThis study provides a first indication of EIC as possible precursor lesion for SOC. This finding could have major clinical implications for future ovarian cancer management and underscores EIC as a possible target for early SOC detection and prevention.

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Role of superoxide dismutase in the fallopian tube function: Immunohistochemical assessment of superoxide dismutase in the fallopian tube.

ACTA HISTOCHEMICA ET CYTOCHEMICA ◽

10.1267/ahc.24.85 ◽

1991 ◽

Vol 24 (1) ◽

pp. 85-91 ◽

Cited By ~ 10

Author(s):

KATSUHIKO NARIMOTO ◽

YOICHI NODA ◽

MASAHIDE SHIOTANI ◽

SATOSHI NATSUYAMA ◽

TAKAHIDE MORI ◽

...

Keyword(s):

Superoxide Dismutase ◽

Fallopian Tube ◽

Tube Function ◽

Immunohistochemical Assessment

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Low Intensity Shockwave Treatment Modulates Macrophage Functions Beneficial to Healing Chronic Wounds

International Journal of Molecular Sciences ◽

10.3390/ijms22157844 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7844

Author(s):

Jason S. Holsapple ◽

Ben Cooper ◽

Susan H. Berry ◽

Aleksandra Staniszewska ◽

Bruce M. Dickson ◽

...

Keyword(s):

Macrophage Activation ◽

Molecular Mechanisms ◽

Chronic Wounds ◽

Immunohistochemical Analysis ◽

Therapeutic Effects ◽

Gene Expressions ◽

Extracorporeal Shock Wave

Extracorporeal Shock Wave Therapy (ESWT) is used clinically in various disorders including chronic wounds for its pro-angiogenic, proliferative, and anti-inflammatory effects. However, the underlying cellular and molecular mechanisms driving therapeutic effects are not well characterized. Macrophages play a key role in all aspects of healing and their dysfunction results in failure to resolve chronic wounds. We investigated the role of ESWT on macrophage activity in chronic wound punch biopsies from patients with non-healing venous ulcers prior to, and two weeks post-ESWT, and in macrophage cultures treated with clinical shockwave intensities (150–500 impulses, 5 Hz, 0.1 mJ/mm2). Using wound area measurements and histological/immunohistochemical analysis of wound biopsies, we show ESWT enhanced healing of chronic ulcers associated with improved wound angiogenesis (CD31 staining), significantly decreased CD68-positive macrophages per biopsy area and generally increased macrophage activation. Shockwave treatment of macrophages in culture significantly boosted uptake of apoptotic cells, healing-associated cytokine and growth factor gene expressions and modulated macrophage morphology suggestive of macrophage activation, all of which contribute to wound resolution. Macrophage ERK activity was enhanced, suggesting one mechanotransduction pathway driving events. Collectively, these in vitro and in vivo findings reveal shockwaves as important regulators of macrophage functions linked with wound healing. This immunomodulation represents an underappreciated role of clinically applied shockwaves, which could be exploited for other macrophage-mediated disorders.

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The Role of microRNAs in the Regulation of Apoptosis in Lung Cancer and Its Application in Cancer Treatment

BioMed Research International ◽

10.1155/2014/318030 ◽

2014 ◽

Vol 2014 ◽

pp. 1-19 ◽

Cited By ~ 26

Author(s):

Norahayu Othman ◽

Noor Hasima Nagoor

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

High Frequency ◽

Tumor Suppressor Genes ◽

Molecular Mechanisms ◽

Lung Carcinogenesis ◽

The Past ◽

Late Stage Diagnosis ◽

Anticancer Treatment

Lung cancer remains to be one of the most common and serious types of cancer worldwide. While treatment is available, the survival rate of this cancer is still critically low due to late stage diagnosis and high frequency of drug resistance, thus highlighting the pressing need for a greater understanding of the molecular mechanisms involved in lung carcinogenesis. Studies in the past years have evidenced that microRNAs (miRNAs) are critical players in the regulation of various biological functions, including apoptosis, which is a process frequently evaded in cancer progression. Recently, miRNAs were demonstrated to possess proapoptotic or antiapoptotic abilities through the targeting of oncogenes or tumor suppressor genes. This review examines the involvement of miRNAs in the apoptotic process of lung cancer and will also touch on the promising evidence supporting the role of miRNAs in regulating sensitivity to anticancer treatment.

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