Publications by authors named "Georgia Karpathiou"

104 Publications

The Immune Microenvironment of Chordomas: An Immunohistochemical Analysis.

Cancers (Basel) 2021 Jul 2;13(13). Epub 2021 Jul 2.

Pathology Department, University Hospital of Saint-Etienne, 42055 Saint-Etienne, France.

Chordomas are rare sarcomas that are usually treated by surgery and/or radiotherapy since these are chemo-resistant tumors, but immunotherapy could be a possible option for chordoma patients. However, few reports investigating the composition of the chordoma immune microenvironment exist. We immunohistochemically studied 81 chordomas regarding their immune microenvironment factors and compared them with clinicopathological data. Macrophages and CD4 cells were the most prominent inflammatory cell populations, followed by CD8 T cells, while CD20 B cells and high endothelial venules (MECA-79+) were less frequently found. PD-L1 (22C3) expression by inflammatory cells was found in 21 (26%) tumors and was associated with a larger tumor size. None of the cases showed the expression of PD-L1 by tumor cells. Survival analysis showed that younger patients had a better overall survival. Considering the immunohistochemical factors studied, higher CD8, the presence of PD-L1+ immune cells, and higher vascular density were adverse prognostic factors, but in multivariate analysis, only PD-L1+ immune cells retained prognostic significance. To conclude, chordoma tumor cells do not express PD-L1, but PD-L1+ immune cells seem to play a negative prognostic role, supporting the need for further studies in this field and the possible beneficial role of immunotherapy in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13133335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268246PMC
July 2021

The Immune Microenvironment of Malignant Pleural Mesothelioma: A Literature Review.

Cancers (Basel) 2021 Jun 26;13(13). Epub 2021 Jun 26.

Department of Pulmonology and Thoracic Oncology, North Hospital, University Hospital of Saint-Etienne, 42055 Saint-Etienne, France.

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour with a poor prognosis, associated with asbestos exposure. Nowadays, treatment is based on chemotherapy with a median overall survival of less than two years. This review highlights the main characteristics of the immune microenvironment in MPM with special emphasis on recent biological advances. The MPM microenvironment is highly infiltrated by tumour-associated macrophages, mainly M2-macrophages. In line with infiltration by M2-macrophages, which contribute to immune suppression, other effectors of innate immune response are deficient in MPM, such as dendritic cells or natural killer cells. On the other hand, tumour infiltrating lymphocytes (TILs) are also found in MPM, but CD4+ and CD8+ TILs might have decreased cytotoxic effects through T-regulators and high expression of immune checkpoints. Taken together, the immune microenvironment is particularly heterogeneous and can be considered as mainly immunotolerant or immunosuppressive. Therefore, identifying molecular vulnerabilities is particularly relevant to the improvement of patient outcomes and the assessment of promising treatment approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13133205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269097PMC
June 2021

Immunohistochemical analysis of L1 cell adhesion molecule and high endothelial venules in breast cancer brain metastasis.

Pathol Res Pract 2021 Jul 13;223:153484. Epub 2021 May 13.

Pathology Department, University Hospital of Saint-Etienne, France.

Background: The vasculature is a crucial factor in tumor development. Vascular co-option achieved by the L1 cell adhesion molecule (L1CAM) and lymphocyte recruitment inside tumors by high endothelial venules (HEVs) are important prognostic factors in primary breast cancer. Their status in breast cancer brain metastasis is unknown.

Aim Of The Study: To explore the status of L1CAMs and HEVs in this tumor compartment.

Material And Methods: Thirty resected breast cancer brain metastases were immunohistochemically studied for L1CAM and MECA-79, an HEV marker. Clinicopathological factors were recorded.

Results: Age at brain metastasis diagnosis ranged from 37 to 80 years (median 55). The time to brain metastasis development after primary tumor diagnosis ranged from 12 to 187 months (median 57). Median overall survival after brain metastasis diagnosis was 29 months. None of the tumors expressed the factors studied.

Conclusion: L1CAM and high endothelial venules are not found in breast cancer brain metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2021.153484DOI Listing
July 2021

STAT6: A review of a signaling pathway implicated in various diseases with a special emphasis in its usefulness in pathology.

Pathol Res Pract 2021 Jul 11;223:153477. Epub 2021 May 11.

Pathology Department, University Hospital of Saint-Etienne, France.

Signal Transducer and Activator of Transcription 6 (STAT6), belonging to a family of seven similar members is primarily stimulated by interleukin(IL)-4 and IL-13, and acts as a T helper type 2 (Th2)-inducing factor. Thus, it is implicated in the pathophysiology of various allergic conditions, such as asthma, atopic dermatitis, eosinophilic esophagitis and food allergies, but also in tumor microenvironment regulation. Furthermore, certain forms of lymphomas, notably the Hodgkin lymphoma group, the primary mediastinal and primary central nervous system lymphoma, as well as some follicular and T cell lymphomas are associated with dysregulation of the STAT6 pathway. STAT6 immunohistochemical expression also serves as a surrogate marker in the diagnosis of solitary fibrous tumor, despite not directly responsible for the tumorigenic effect. These pathophysiological implications of the STAT6 pathway, its diagnostic or prognostic role in pathology, as well its immunohistochemical detection with different antibodies will be discussed in this review.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2021.153477DOI Listing
July 2021

Patterns of brachyury expression in chordomas.

Ann Diagn Pathol 2021 Aug 10;53:151760. Epub 2021 May 10.

Pathology Departments, University Hospital of Saint-Etienne, France. Electronic address:

Introduction: Chordomas are rare malignant midline tumors, presumed to arise from notochordal remnants. This was further suggested by the discovery of the brachyury in chordomas pathogenesis. Its immunohistochemical expression has become the principal adjunct in the diagnosis of chordomas. However, studies about brachyury expression in chordomas are not fully comparable, mainly because they use different primary antibodies. Thus, the aim of this study is to investigate the expression of brachyury expression in a series of chordomas in conjunction to clinicopathological characteristics and to review the relevant literature providing all the details needed in the immunohistochemical study of brachyury.

Materials And Methods: This is a retrospective study of 62 chordomas, diagnosed over a 22-year period. No dedifferentiated or poorly differentiated cases were included. A monoclonal primary antibody (clone A-4) was used and brachyury expression was evaluated by the H-score. Clinicopathological parameters studied were age, sex, tumor localization, decalcification status and tissue age. Fetal notochords were used for comparison.

Results: Mean H-score of nuclear brachyury expression was 129.8. The tissue age significantly influenced brachyury expression, the older samples expressing less brachyury. Decalcification demonstrated a trend to weaken brachyury expression. Clinical characteristics were not correlated with the patterns of brachyury expression. Notochords were negative. Literature review reveals several polyclonal antibodies used and a positivity of 75%-100% in chordomas with even more variable results in notochords.

Conclusion: In chordomas, as in other tumor types, an uniformization of studies about brachyury expression is needed, by considering the clone used, and the decalcification and the age of the sample, given the growing importance of brachyury in diagnosis and therapeutic steps.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anndiagpath.2021.151760DOI Listing
August 2021

Molecular Analysis of an Abdominal Wall Cesarean Section Endometrioid Carcinoma.

Int J Surg Pathol 2021 May 14:10668969211018262. Epub 2021 May 14.

University Hospital of Saint-Etienne, France.

Malignant transformation of endometriosis is rare, and most cases concern the ovaries, while extraovarian cases are mostly found in the rectovaginal septum. Incisional adenocarcinoma is extremely rare, with only few cases reported in the literature, while their molecular profile remains unknown. Thus, we report on an abdominal wall cesarean section scar endometrioid adenocarcinoma studied by next-generation sequencing and microsatellite instability analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/10668969211018262DOI Listing
May 2021

Autophagic Markers in Chordomas: Immunohistochemical Analysis and Comparison with the Immune Microenvironment of Chordoma Tissues.

Cancers (Basel) 2021 Apr 30;13(9). Epub 2021 Apr 30.

Pathology Department, University Hospital of Saint-Etienne, 42055 Saint-Etienne, France.

Chordomas are notably resistant to chemotherapy. One of the cytoprotective mechanisms implicated in chemoresistance is autophagy. There are indirect data that autophagy could be implicated in chordomas, but its presence has not been studied in chordoma tissues. Sixty-one (61) chordomas were immunohistochemically studied for autophagic markers and their expression was compared with the expression in notochords, clinicopathological data, as well as the tumor immune microenvironment. All chordomas strongly and diffusely expressed cytoplasmic p62 (sequestosome 1, SQSTM1/p62), whereas 16 (26.2%) tumors also showed nuclear p62 expression. LC3B (Microtubule-associated protein 1A/1B-light chain 3B) tumor cell expression was found in 44 (72.1%) tumors. Autophagy-related 16‑like 1 (ATG16L1) was also expressed by most tumors. All tumors expressed mannose-6-phosphate/insulin-like growth factor 2 receptor (M6PR/IGF2R). LC3B tumor cell expression was negatively associated with tumor size, while no other parameters, such as age, sex, localization, or survival, were associated with the immunohistochemical factors studied. LC3B immune cell expression showed a significant positive association with programmed death-ligand 1 (PD-L1)+ immune cells and with a higher vascular density. ATG16L1 expression was also positively associated with higher vascular density. Notochords ( = 5) showed different immunostaining with a very weak LC3B and M6PR expression, and no p62 expression. In contrast to normal notochords, autophagic factors such as LC3B and ATG16L1 are often present in chordomas, associated with a strong and diffuse expression of p62, suggesting a blocked autophagic flow. Furthermore, PD-L1+ immune cells also express LC3B, suggesting the need for further investigations between autophagy and the immune microenvironment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13092169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124629PMC
April 2021

FOXA1 Expression by Immunohistochemistry in Carcinosarcomas of the Endometrium and Ovary/Fallopian Tube.

Int J Gynecol Pathol 2021 Mar 24. Epub 2021 Mar 24.

Pathology Department (G.K., P.D.C., M.P.) Gynecology and Obstetrics Department (C.C.), North Hospital, University Hospital of Saint-Etienne, France.

FOXA1, a transcription factor essential for the binding of other transcription factors on chromatin, is associated with hormone receptor-associated cancers, such as breast and endometrial cancer. It is also considered an antagonist of epithelial-to-mesenchymal transition (EMT). In endometrial cancer, FOXA1 is considered a tumor suppressor; in carcinosarcoma, one of the most aggressive and rare subtypes of endometrial cancer, thought to be derived through an EMT mechanism, FOXA1 has not been studied. Thus, the aim of this study was to investigate the possible expression of FOXA1 in carcinosarcomas, and its correlation with clinicopathologic factors. This was a retrospective study of 31 patients diagnosed with carcinosarcomas of the uterus or the adnexa. Histologic and clinical factors were correlated with the immunohistochemical expression of FOXA1. FOXA1 was expressed by 38.7% of the carcinomatous components and 16.1% of the sarcomatous components. FOXA1-positive sarcomatous components were seen only with positive carcinomatous components (P=0.004). FOXA1 expression was not associated with age, primary tumor site, stage, metastases, overall survival, or tumor relapse. FOXA1 expression in the carcinomatous component was associated with an absence of lymphovascular invasion or the presence of heterologous components. FOXA1 expression in the sarcomatous component was associated with rhabdomyosarcoma, rather than the chondrosarcoma heterologous component. Carcinosarcomas harbor FOXA1 expression, although it is in their carcinomatous rather than sarcomatous components, suggesting a possible role of FOXA1 in the EMT of carcinosarcomas. FOXA1 shows no prognostic significance in this tumor group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PGP.0000000000000772DOI Listing
March 2021

Senescence, immune microenvironment, and vascularization in cardiac myxomas.

Cardiovasc Pathol 2021 May-Jun;52:107335. Epub 2021 Mar 21.

Pathology Department, University Hospital of Saint-Etienne, Saint-Priest-en-Jarez, France.

Aims: Cardiac myxomas are rare tumors of incompletely elucidated pathogenesis. The aim of this study is to explore the possible presence of a senescence phenotype in cardiac myxomas, associated with an inflammatory and vasculogenic tumor microenvironment.

Methods And Results: This is a retrospective study of 29 cardiac myxomas with immunohistochemical detection of various inflammatory, vascular, and senescence markers. We show that all myxomas contain tumor cells in senescence overexpressing p16, and a fraction of senescent endothelial cells. Macrophages are the principal inflammatory cell population, followed by cytotoxic T cells, with fewer plasma cells, mastocytes, and B lymphocytes. These populations are found in different intratumoral localizations. Larger tumor volume is associated with a lower percentage of myxoid matrix, higher cellularity, higher macrophage, and lower number of mast cells as well as higher PD-L1 expression by inflammatory cells. Higher vascular density is associated with higher percentage of B cells, a lower number of macrophages and higher number of mastocytes, and lower PD-L1 expression by inflammatory cells. Tumors with higher vascular density and higher cellularity show higher amounts of p16 senescent endothelial cells.

Conclusions: Myxoma tumor cells are in senescence and reside inside a tumor microenvironment with a distinct inflammatory profile rich in macrophages and cytotoxic T cells, and a rich vasculature, probably attributed to a senescence-associated secretory phenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carpath.2021.107335DOI Listing
March 2021

High endothelial venules are present in pharyngeal and laryngeal carcinomas and they are associated with better prognosis.

Pathol Res Pract 2021 Apr 18;220:153392. Epub 2021 Feb 18.

Departments of Pathology, North Hospital, University Hospital of St-Etienne, France.

Background: Tumors lymphocytic infiltration has prognostic and predictive value. However, the mechanisms involved in lymphocyte recruitment remain poorly characterized. High endothelial venules (HEV) are blood vessels specialized in lymphocyte recruitment, recently showing prognostic significance in some types of cancer. Their implications in laryngeal or pharyngeal cancer is largely unknown.

Aim Of The Study: To investigate the possible presence of HEVs in head and neck cancer.

Material And Methods: Oropharyngeal (n = 61), hypopharyngeal (n = 53) and laryngeal (n = 21) squamous cell carcinomas were immunohistochemically studied with the MECA-79 antibody, which specifically recognizes HEVs. Histological and clinical factors were correlated with HEVs' presence.

Results: HEVs were present in 34% of tumors, showing significant correlations with oropharyngeal localization, higher lymphocytic response, lower tumor budding, lower T status, absence of distant metastases and better overall and progression-free survival.

Conclusion: HEVs represent an important prognostic factor in head and neck cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2021.153392DOI Listing
April 2021

INSM1 Expression in Chordomas.

Am J Clin Pathol 2021 Feb 25. Epub 2021 Feb 25.

Pathology Department, University Hospital of Saint-Etienne, Saint-Etienne, France.

Objectives: Chordomas are rare malignant tumors with a broad differential diagnosis, including chondrosarcomas and metastatic carcinomas. Recently, insulinoma-associated protein 1 (INSM1) has gained great interest regarding the diagnosis of neuroendocrine tumors but also extraskeletal myxoid chondrosarcomas. However, its expression in chordomas remains largely unknown.

Methods: We retrospectively examined 57 chordomas for INSM1 expression.

Results: INSM1 expression was found in only 5% of tumors.

Conclusions: This marker is rarely expressed in this type of tumor, raising questions about neuroendocrine differentiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcp/aqaa250DOI Listing
February 2021

The Effect of Strontium Ranelate on Fracture Healing: An Animal Study.

Biomed Res Int 2020 24;2020:1085324. Epub 2020 Nov 24.

Democritus University of Thrace, Alexandroupolis 68100, Greece.

Background: trontium ranelate (StR) is an antiosteoporotic agent previously utilized for the enhancement of fracture union. We investigated the effects of StR on fracture healing using a rabbit model.

Methods: Forty adult female rabbits were included in the study and were divided in 2 equal groups, according to StR treatment or untreated controls. All animals were subjected to osteotomy of the ulna, while the contralateral ulna remained intact and served as a control for the biomechanical assessment of fracture healing. Animals in the study group received 600 mg/kg/day of StR orally. All animals received ordinary food. At 2 and 4 weeks, all animals were euthanatized and the osteotomy sites were evaluated for healing through radiological, biomechanical, and histopathological studies.

Results: The treatment group presented statistically significant higher callus diameter, total callus area, percentage of fibrous tissue ( < 0.001), vessels/mm, number of total vessels, and lower osteoclast number/mm ( < 0.05) than the control group at 2 weeks. Additionally, the treatment group presented significantly higher percentages of new trabecular bone, vessels/mm, osteoclast number/mm, and lower values for callus diameter, as well as total callus area ( < 0.05), than the control group at 4 weeks. At 4 weeks, in the treatment group, force applied ( = 0.003), energy at failure ( = 0.004), and load at failure ( = 0.003) were all significantly higher in the forearm specimens with the osteotomized ulnae compared to those without. Radiological bone union was demonstrated for animals receiving StR at 4 weeks compared with controls ( = 0.045).

Conclusion: StR appears to enhance fracture healing but further studies are warranted in order to better elucidate the mechanisms and benefits of StR treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/1085324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768587PMC
November 2020

Vascular Pseudoinvasion After Endometrial Ablation.

Int J Gynecol Pathol 2020 Dec 14. Epub 2020 Dec 14.

Pathology Department (G.K., S.D., M.P.) Gynecology and Obstetrics Department (T.C., C.C.), University Hospital of Saint-Etienne, Saint-Etienne, France.

Vascular pseudoinvasion or displacement of tumor or normal endometrial tissue is a potential pitfall in uterine pathology. The proposed mechanisms of this phenomenon are mostly associated with the uterine manipulator used during minimally invasive hysterectomies. The aim of this report is to describe vascular pseudoinvasion in a still unreported setting, that of a postendometrial ablation hysterectomy, and to provide a summary of studies dealing with artifactual or nonmalignant myometrial vessel involvement by normal or neoplastic endometrial tissue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PGP.0000000000000748DOI Listing
December 2020

Mesothelial Cysts.

Am J Clin Pathol 2021 05;155(6):853-862

Pathology Department, University Hospital of Saint-Etienne, Saint-Etienne, France.

Objectives: Peritoneal mesothelial cysts have been reported under various terms, including benign cystic mesothelioma, usually in the form of case reports/series, whereas extraperitoneal cases are rarely reported. Our objective was to report the detailed characteristics of cystic lesions of the serosal cavities.

Methods: We retrospectively examined the clinicopathologic findings of a series of mesothelial cystic lesions (n = 79).

Results: Most cases (n = 68, 86%) concerned the peritoneum, whereas 11 (14%) concerned the pericardium. No pleural cases were found. A total of 51 (64.5%) lesions were solitary, whereas 28 (35.5%) were multiple. Peritoneal lesions harbored a plump eosinophilic mesothelium and a loose connective stroma, whereas pericardial lesions showed a cuboidal/flattened mesothelium, collagenous stroma, intense inflammation, and other tissue types, like adipose and muscle tissue. Solitary peritoneal lesions are usually extrapelvic and found in older patients incidentally during other surgeries, whereas multiple lesions are found in younger patients and usually in the pelvis. The lesions show a benign clinical course with rare recurrences but no malignant transformation.

Conclusions: Most mesothelial cysts are peritoneal and rarely pericardial. Peritoneal cysts differ from pericardial cysts. Peritoneal solitary lesions differ from multiple lesions, also suggesting their pathogenetic differences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcp/aqaa189DOI Listing
May 2021

Vascular Involvement: An Uncommon Histologic Finding of Rectal Endometriosis.

Int J Gynecol Pathol 2020 Nov 24. Epub 2020 Nov 24.

Pathology Institute of Hospices Civils de Lyon, Groupement Hospitalier Est, University Hospital of Lyon, Bron (M.M., T.F., P.-M.L., M.R., V.H.) Department of Pathology, University Hospital of Saint-Etienne, Saint-Etienne (G.K.), France Department of Pathology, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia (M.M.).

Deep infiltrating endometriosis frequently affects the rectosigmoid region. It clinically presents as a chronic painful condition affecting women in their reproductive time. Here, we present a case of a 28-yr-old female patient who had a history of dysmenorrhea, dyspareunia, chronic abdominal and pelvic pain, and constipation secondary to rectal wall endometriosis. Microscopic examination of the resected rectal segment showed endometriosis with vascular and lymph node involvement. Vascular involvement is an uncommon histologic finding that may raise concern for potential malignancy. The aim of this report is to alert pathologists and physicians about this infrequent pitfall that can be mistaken for a neoplastic process and to discuss the underlying pathophysiology of vascular involvement by endometrial tissue in otherwise benign conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PGP.0000000000000734DOI Listing
November 2020

Local Anesthesia Thoracoscopy with versus without Midazolam: A Randomized Controlled Trial.

Respiration 2020;99(9):789-799. Epub 2020 Nov 18.

Department of Respiratory Medicine, Medical School of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece,

Background: Medical thoracoscopy is the gold standard for the diagnosis of pleural diseases. To date, no consensus exists regarding the choice of sedative and analgesic agents in patients undergoing local anesthetic thoracoscopy (LAT), and questions are raised as to whether sedatives may add to respiratory side effects.

Objective: The aim of the study was to test the hypothesis that administration of midazolam associated with lidocaine versus lidocaine alone in patients with LAT adds to respiratory side effects.

Methods: We randomly assigned 80 patients to a 1:1 study to 2 groups: local anesthesia by lidocaine (n = 40) versus lidocaine and midazolam (n = 40), with the primary end point being the mean lowest oxygen saturation. The secondary end points were cardiovascular parameters, complications, days of drainage, hospital stay, and patients' quality of life (QoL) as assessed by a visual analog scale (VAS).

Results: The mean age of all patients was 66.6 ± 13.1 years. The study comprised 50 males (62.5%). No difference was observed in the demographics between the 2 groups. No significant difference was observed between the 2 groups in oxygen saturation (primary end point). A significant difference was observed in favor of the midazolam group regarding the QoL assessed by VAS.

Conclusion: Midazolam does not add to respiratory side effects when it is used with lidocaine for LAT, while patients' QoL is actually improved in this group. Therefore, in our department, we changed our startegy in favor of the association of lidocaine and midazolam.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000509761DOI Listing
November 2020

Chemotherapy-induced changes in bronchoalveolar lavage fluid CD4 + and CD8 + cells of the opposite lung to the cancer.

Sci Rep 2020 11 16;10(1):19927. Epub 2020 Nov 16.

Department of Respiratory Medicine, Medical School of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece.

Published articles support the effect of chemotherapy in the immune environment of tumors, including lung carcinomas. The role of CD4 + T-cells is crucial for expansion and accumulation of other antigen-specific immune cells, and the participation of CD8 + cells in tumor killing activity has been confirmed by many studies. However, little is known about the effect of chemotherapy on the healthy lung parenchyma from lung cancer patients, and whether there are differences between the different chemotherapy compounds used to treat this patient population. The aim of our study was to explore the effect of chemotherapy on CD4 + and CD8 + cells in the bronchoalveolar lavage fluid (BALF) of the healthy lung in patients treated with standard chemotherapy regimens. Fifteen patients underwent BAL, in the healthy lung before and after six chemotherapy courses. Platinum-based regimens included vinolerbine (VN) in 6 patients, gemcitabine (GEM) in 4 patients and etoposide (EP) in 5 patients. All patients but one were males and smokers (93%). The median age of patients was 56 years (42-75). No significant difference was noted in the patients' age between the three treated groups. Furthermore, between the three groups, no significant changes in the means of CD4 + and CD8 + cells were noted. However, when we compared the mean CD4 + cells before and after chemotherapy within each group, changes were noted when comparing VN before versus after (p = 0.05), GEM before versus after (p = 0.03), and EP before versus after (p = 0.036). In our pilot study, changes were noted in BALF CD4 + cells for the three most applied regimens at the normal lung parenchyma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-76752-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670451PMC
November 2020

Molecular analysis of a uterine broad ligament leiomyoma in a patient with CLOVES syndrome.

Pathol Res Pract 2020 Dec 9;216(12):153285. Epub 2020 Nov 9.

Pathology Department, University Hospital of Saint-Etienne, France.

Overgrowth syndromes are characterized by a global or regional excess growth of various tissue types, especially of mesenchymal nature. The CLOVES (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined-type Vascular malformations, Epidermal naevi, Scoliosis/Skeletal and spinal anomalies) syndrome is characterized by an asymmetric growth excess associated with PIK3CA mutations, found in mosaic, affecting the lesional, but not the normal tissues. Herein, we report the case of a patient affected by CLOVES syndrome, harboring a 13 cm leiomyoma of the uterine broad ligament. The leiomyoma tissue was examined by next-generation sequencing showing the absence of related mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2020.153285DOI Listing
December 2020

Old Player-New Tricks: Non Angiogenic Effects of the VEGF/VEGFR Pathway in Cancer.

Cancers (Basel) 2020 Oct 27;12(11). Epub 2020 Oct 27.

Department of Medical Oncology, University Hospital of Ioannina, 45500 Ioannina, Greece.

Angiogenesis has long been considered to facilitate and sustain cancer growth, making the introduction of anti-angiogenic agents that disrupt the vascular endothelial growth factor/receptor (VEGF/VEGFR) pathway an important milestone at the beginning of the 21st century. Originally research on VEGF signaling focused on its survival and mitogenic effects towards endothelial cells, with moderate so far success of anti-angiogenic therapy. However, VEGF can have multiple effects on additional cell types including immune and tumor cells, by directly influencing and promoting tumor cell survival, proliferation and invasion and contributing to an immunosuppressive microenvironment. In this review, we summarize the effects of the VEGF/VEGFR pathway on non-endothelial cells and the resulting implications of anti-angiogenic agents that include direct inhibition of tumor cell growth and immunostimulatory functions. Finally, we present how previously unappreciated studies on VEGF biology, that have demonstrated immunomodulatory properties and tumor regression by disrupting the VEGF/VEGFR pathway, now provide the scientific basis for new combinational treatments of immunotherapy with anti-angiogenic agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12113145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692709PMC
October 2020

Immune cells in normal pregnancy and gestational trophoblastic diseases.

Placenta 2020 11 8;101:90-96. Epub 2020 Sep 8.

Department of Anatomy-Histology-Embryology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece. Electronic address:

A healthy pregnancy requires the development of maternal-fetal immune tolerance against the semi-allogeneic fetus. The interactions between the trophoblastic cells and the maternal immune cells (p.e., natural killer cells, T cells, macrophages, dendritic cells and B-cells) are important for the development of the maternal-fetal immune tolerance and the placental growth and function. These interactions are mediated by cell to cell contact and secreted molecules such as cytokines, chemokines, angiogenic factors and growth factors. The maternal immune cells are present in normal non-pregnant and pregnant endometrium and there are several lines of evidence based on immunohistochemical and RNA sequencing data that the decidual immune cells and immune-related pathways display alterations in GTD, which may have pathogenetic and clinical significance. The present review focuses on the usefulness of the immunohistochemical analysis which provides multiparametric in situ information regarding the numbers, the immunophenotypes and the immunotopographical distributions of the decidual immune cells in tissue sections from normal pregnancy and GTD. We also discuss the significance of the immunohistochemical information in order to gain insight in the putative mechanisms explaining the alterations of the decidual immune cells in GTD and the potential implications of these alterations in the pathogenesis and the clinical behavior of GTD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.placenta.2020.09.006DOI Listing
November 2020

The transcriptional factors CDX2 and FOXA1 in chordomas.

Pathol Res Pract 2020 Nov 12;216(11):153160. Epub 2020 Aug 12.

Pathology Department, University Hospital of Saint-Etienne, France. Electronic address:

Chordomas are rare osseous tumors believed to originate from notochordal remnants through brachyury activation. CDX2 and FOXA1 are both induced by brachyury, but their expression has not been studied in chordomas. We retrospectively studied the immunohistochemical expression of these two factors in 57 chordomas, finding that CDX2 is not expressed in these tumors. FOXA1 expression was found in 7 (12.3%) tumors. No association of FOXA1 expression with clinical factors was found. Thus, CDX2 expression is not a feature of chordomas, while a limited expression of FOXA1 is seen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2020.153160DOI Listing
November 2020

CD56 is Expressed in Uterine Smooth Muscle Tumors.

Int J Gynecol Pathol 2021 Jul;40(4):315-323

CD56 is used in gynecologic pathology, typically in the context of a neuroendocrine, sex cord or sex cord-like tumor. It has never been studied in uterine smooth muscle tumors, which can potentially enter their differential diagnosis, and thus CD56 positivity could potentially be a pitfall. Thus, the aim of this study was to explore its expression in this category of tumors. Seventy-eight uterine smooth muscle tumors, including 14 leiomyosarcomas, 46 leiomyomas and their variants, 14 smooth muscle tumors of uncertain malignant potential, and 4 intravenous leiomyomatoses were studied in regard to CD56 expression. Fifty-eight nearby myometria were also analyzed. Sixty-five (83.4%) tumors showed CD56 expression. Nearby myometrium showed CD56 expression in 15 cases (25.9%). Staining ranged from 10% to 100% of tumor or myometrial cells (median 80% and 50%, respectively). Among the tumor types, leiomyoma with bizarre nuclei, had the lowest extensive expression (P=0.01). Most uterine smooth muscle neoplasms express CD56; thus, it is not useful in attempting to discriminate from endometrial stromal or sex cord-like neoplasms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PGP.0000000000000696DOI Listing
July 2021

Cell Therapy for Idiopathic Pulmonary Fibrosis: Rationale and Progress to Date.

BioDrugs 2020 Oct;34(5):543-556

First Academic Department of Pneumonology, National and Kapodistrian University of Athens, Athens, Greece.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by progressive lung scarring due to unknown injurious stimuli ultimately leading to respiratory failure. Diagnosis is complex and requires a combination of clinical, laboratory, radiological, and histological investigations, along with exclusion of known causes of lung fibrosis. The current understanding of the disease etiology suggests an interaction between genetic factors and epigenetic alterations in susceptible, older individuals. Prognosis is dismal and current treatment options include anti-fibrotic agents that only slow down disease progression and carry considerable side effects that hamper patients' quality of life. Therefore, the need for new, more effective treatments, alone or in combination with existing pharmacotherapy, is sorely needed. Regenerative medicine, the potential use of cell therapies to treat destructive diseases that cause architectural distortion to the target organ, has also emerged as an alternative therapeutic for lung diseases with unfavorable prognosis such as IPF. Mesenchymal stem cells (MSCs) and type II alveolar epithelial cells (AEC2s) have been used and their safety has been demonstrated. In the case of MSCs, both homogenic and allogeneic sources have been used and both are considered viable options without immunosuppressive therapy, taking into consideration the absence of immunogenicity and HLA response. AEC2s have been used in one trial with promising results but their use requires a deceased donor and immunosuppressive pre-treatment. In this review, we briefly summarize the current state of knowledge regarding the pathogenesis of IPF, and the background and rationale for using MSCs or AEC2s as potential treatment options. We list and describe the clinical trials completed to date and provide a comparison of their methods and results as well as a possible way forward.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40259-020-00437-8DOI Listing
October 2020

Maxillary Ameloblastoma: A Review With Clinical, Histological and Prognostic Data of a Rare Tumor.

In Vivo 2020 Sep-Oct;34(5):2249-2258

Department of Pathology and Otorhinolaryngology, University Hospital of Ioannina, Ioannina, Greece

Diagnosis of odontogenic tumors can be challenging due to their rarity and diverse morphology, but when arising near the tooth, the diagnosis could be suspected. When their location is not typical, like inside the paranasal sinuses, the diagnosis is less easy. Maxillary ameloblastomas are exceedingly rare with only sparse information on their epidemiological, histological and genetic characteristics. The aim of this report is to thoroughly review the available literature in order to present the characteristics of this tumor. According to available data, maxillary ameloblastomas can occur in all ages but later than mandible ones, and everywhere within the maxillary region without necessarily having direct contact with the teeth. No sex preference has been shown. The most common histological patterns seen in this location are the follicular and plexiform ones. Maxillary ameloblastomas are locally aggressive neoplasms, thus therapy aims for excision including normal bone beyond the lesion. In contrast to mandible ameloblastomas, maxillary ones most commonly show mutations of the SMO gene. Furthermore, differential tumor diagnosis is thoroughly discussed in the present review.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/invivo.12035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652510PMC
June 2021

Brain metastasis PD-L1 and CD8 expression is dependent on primary tumor type and its PD-L1 and CD8 status.

J Immunother Cancer 2020 08;8(2)

Pathology, University Hospital of Saint-Etienne, Saint-Etienne, France.

Background: Brain metastases (Bmets) are frequent; however, limited data exist on the efficacy of immunotherapy in these lesions. The aims of the study were to analyze the immunohistochemical expressions of programmed death ligand 1 (PD-L1) and CD8 in Bmets and to compare them with their expressions in paired primary tumors, as well as correlate the results with clinicopathological features.

Methods: This is a retrospective study of 233 patients with Bmets and 111 paired primaries. Clinical, histological, and molecular data were recorded and compared with the immunohistochemical results of PD-L1 and CD8 expressions. The statistical analysis included χ test, Cramer's V test, factorial analyses of variance, simple regression analysis, and Kaplan-Meier analysis with log-rank product limit estimation.

Results: PD-L1 expression was found in 23.6% of Bmets and in 29.0% of primary tumors with concordant expression between them in 75.5% of cases. Bmets PD-L1 expression was associated with primary tumor PD-L1 expression and the primary tumor type. Significant CD8 peritumoral expression was found in 68.6% of Bmets and in 87.7% of primary tumors. CD8 expression was concordant between primary and metastatic tumors in 73.3% of cases. Bmets CD8 expression was associated with primary tumor CD8 expression and primary tumor type. PD-L1 expression was associated with CD8 expression in both primary and metastatic tumors. The concordance between primary and metastatic tumor PD-L1 expression was independent of all factors studied. The concordance between primary and metastatic CD8 expressions was marginally associated to the time of Bmets development. No prognostic role for PD-L1 and CD8 expression in Bmets was found.

Conclusion: PD-L1 and CD8 Bmets expressions are associated with the primary tumor type and its PD-L1 and CD8 expressions. No factor predicts the discordance for PD-L1 expression, while time to Bmets development is associated with CD8 expression discordance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jitc-2020-000597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454240PMC
August 2020

Chordomas: A review with emphasis on their pathophysiology, pathology, molecular biology, and genetics.

Pathol Res Pract 2020 Sep 29;216(9):153089. Epub 2020 Jun 29.

Pathology Department, University Hospital of Saint-Etienne, France.

Chordomas are uncommon, bone, axial, or (rarely) extra-axial tumors that are malignant and frequently recur but less commonly metastasize. They usually affect adults, with a very small proportion being pediatric tumors. For children, such tumors present a different biology, since they are more common as scull rather than sacral tumors, with aggressive histological features, including a loss of SMARCB1/INI1 and a dismal prognosis. Histologically, chordomas, believed to derive from notochordal tissue, characteristically show physaliphorous cells in a myxoid or chondroid matrix. Dedifferentiated and poorly differentiated forms can be observed. Moreover, a grading scale for chordomas has been proposed. Cytokeratin, EMA, S100, and brachyury are expressed by most chordomas. These are chemo-resistant tumors, for which surgical resection and/or radiotherapy are the treatments of choice. In this review, the histological, immunohistochemical, molecular, and clinical data of chordomas are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2020.153089DOI Listing
September 2020

Occupational exposures in constrictive bronchiolitis.

Pathol Res Pract 2020 Sep 18;216(9):153069. Epub 2020 Jun 18.

Department of Pathology, University Hospital of Saint-Etienne, CEDEX 2, St-Etienne, 42055, France. Electronic address:

Bronchiolitis obliterans is a clinical entity which results from a variety of etiologies and has a detrimental impact on patients' quality of life when it remains undiagnosed and untreated. Due to its non-pathognomic clinical symptoms and signs, physicians often proceed to radiological examination, especially with high resolution chest tomography. Histological examination reveals constrictive bronchiolitis, the pathological definition of bronchiolitis obliterans. Due to an almost normal aspect of the lung parenchyma this condition can be missed. However, its recognition and the identification of a possible exposure are important for removing the patient from the incriminating agent. We present a case of constrictive bronchiolitis in a metal-cutting worker, highlighting the principal findings of this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2020.153069DOI Listing
September 2020

Adenomatoid Tumor: A Review of Pathology With Focus on Unusual Presentations and Sites, Histogenesis, Differential Diagnosis, and Molecular and Clinical Aspects With a Historic Overview of Its Description.

Adv Anat Pathol 2020 Nov;27(6):394-407

Pathology Department, University Hospital of Saint-Etienne, Saint-Etienne, France.

Adenomatoid tumors have been described almost a century ago, and their nature has been the subject of debate for decades. They are tumors of mesothelial origin usually involving the uterus, the Fallopian tubes, and the paratesticular region. Adenomatoid tumors of the adrenal gland, the liver, the extragenital peritoneum, the pleura, and the mediastinum have been rarely reported. They are usually small incidental findings, but large, multicystic and papillary tumors, as well as multiple tumors have been described. Their pathogenesis is related to immunosuppression and to TRAF7 mutations. Despite being benign tumors, there are several macroscopic or clinical aspects that could raise diagnostic difficulties. The aim of this review was to describe the microscopic and macroscopic aspects of adenomatoid tumor with a special focus on its differential diagnosis and pathogenesis and the possible link of adenomatoid tumor with other mesothelial lesions, such as the well-differentiated papillary mesothelioma and the benign multicystic mesothelioma, also known as multilocular peritoneal cysts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAP.0000000000000278DOI Listing
November 2020

An immunohistochemical analysis of CD3, PD-L1, and CTLA-4 expression in carcinosarcomas of the gynecological tract and their metastases.

Pathol Res Pract 2020 Aug 21;216(8):153028. Epub 2020 May 21.

Department of Pathology, North Hospital, University Hospital of St-Etienne, France.

Background: Carcinosarcoma of the gynecological tract is a rare tumor with a dismal prognosis. Its immune micro-environment has not been sufficiently studied.

Aim Of The Study: To study the immune micro-environment of gynecological carcinosarcomas.

Material And Methods: Sixty-nine surgical specimens from 37 different patients, including 34 primary tumors and 35 metastases, were immunohistochemically studied for the expression of CD3, PD-L1, and CTLA-4. Clinical and histological features were recorded and correlated with immunohistochemical factors.

Results: Twenty-two cases involved the uterine corpus, 1 the uterine cervix, and 14 the adnexa. The overall survival ranged from 2 to 156 months, with a median survival of 16 months. CD3 expression was more frequent at the sarcomatous than the carcinomatous component. CTLA-4 expression was higher at the carcinomatous than the sarcomatous component. PD-L1 was negative in all cases studied. Tumor relapse, metastasis presence, metastasis localization, and overall survival did not correlate with CD3 or CTLA-4 expression.

Conclusion: PD-L1 expression is not a feature of gynecological carcinosarcomas, despite a relatively frequent lymphocytic reaction. CTLA-4 expression is sometimes found in these tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2020.153028DOI Listing
August 2020
-->