Open Access Pub publishes peer-reviewed, free-to-read open-access articles. Showing
articles matching immunohistochemistry — open any to read the full text,
or download the PDF or XML.
May 2025 DOI 10.14302/issn.2379-8572.joa-25-5504
Introduction Angiosarcoma is a rare malignant tumour from fast-evolving and aggressive vascular endothelial cells that accounts for 1% of all sarcomas. The sinus location of angiosarcoma is exceptional. The clinical polymorphism of this tumour may cause a delay in diagnosis. Risk factors are not always understood. However, a history of radiation therapy for locoregional cancer and/or lymphedema is most commonly found. The prognosis remains bleak with an overall five-year survival of 35 to 40%. Objectives The authors discuss the diagnostic, therapeutic and prognostic modalities and difficulties of this tumour. Observation: The authors report a case of maxillary sinus angiosarcoma confirmed by radio-induced secondary CD34 immunohistological staining in a 40-year-old man having a history of hemangioendothelioma treated with conservative endoscopic surgery and adjuvant radiotherapy 15 months earlier. Discussion This lesion is rare in the ENT sphere and may be confused with a benign tumor in its early stages. Only histological examination with immunohistochemistry can confirm the diagnosis (factor VIII, CD34 and CD31 antigens). Treatment consists of a wide resection followed by radiotherapy, hence the need for early diagnosis in the metastatic phase, first-line treatments include doxorubicin or paclitaxel weekly. Conclusion Radio-induced angiosarcoma is a rare malignant tumour, it occurs in patients who have received conservative treatment and radiation therapy for nasosinusitis cancers. Angiosarcomas of the nasal passages remain a diagnostic and therapeutic challenge due to their local and general aggressiveness.
Dec 2022 DOI 10.14302/issn.2574-4526.jddd-22-4151
Steroid cell tumors of the ovary are particularly rare, secreting sex hormones, characterized by steroid cell proliferation and represent only 0.1% of all ovarian tumors. They are classified into three subtypes according to their cell of origin: stromal luteoma, Leydig cell tumors and a third subtype of unknown lineage corresponds to a not specified steroid cell tumor (SCT-NOS). This third subtype accounts for 60% of steroid cell tumors. The clinical manifestations of SCT-NOS can take many forms, including pain, abdominal distension, but perhaps the most visible presentations are those related to hormonal activity and virilization of the tumor. We present a rare case of a 48-year-old woman with vaginal bleeding and a history of trunk obesity, hirsutism for 2 years and hypothyroidism with hormone replacement therapy. Clinical examination revealed a characteristic of obesity, virilization. Serum testosterone was 3.62 µg / L and CA-125 was 40.67. Magnetic resonance imaging identified a left ovarian solid mass and histopathology confirmed a steroid cell tumor not specific. The patient underwent exploratory laparotomy and left salpingoophorectomy. Macroscopically, the mass is well circumscribed, solid, homogeneous and yellowish. Microscopically, the tumor is mainly composed of eosinophilic or vacuolar granular cytoplasm. Immunohistochemistry showed that the tumor cells were strongly positive for inhibin. The postoperative period was uneventful. Through this rare observation, we will discuss the aspects that characterize this type of tumor and present some guidelines to be used in the differential diagnosis, as well as the difficulties encountered in the clinical, radiological and therapeutic fields.
Jan 2022 DOI 10.14302/issn.2372-6601.jhor-22-4061
Background Human malignant cell models which reflect the structural and physiological complexity of tumor tissue are of great importance for preclinical research in oncology. Spheroids/tumoroids derived from solid tumors are of great interest as cellular models mimicking the first vascular-free growth phase of a tumor node. The fact of the identity between artificially created tumor multicellular aggregates and the real tumor tissue, however, needs to be specified, described and validated in order to see how closely the spheroids are biologically similar to the malignized tissues in vivo compared to the monolayer cell cultures traditionally used. We present here a comparison study of the characteristics of solid tumor cells of different histogenesis (melanomas, soft tissue sarcomas and bone sarcomas, epithelial tumors) cultured in two dimensions (monolayer culture) and three dimensional space (spheroid), namely: spatial organization, multiplication, metabolic activity. Patients and Methods For the creation of 2 D and 3D cell models the cells isolated from the patient's solid tumor fragments obtained intraoperatively were used. 15 samples of skin melanoma, 20 samples of soft tissue and osteogenic sarcomas (STBS), and 9 samples of epithelial tumors (ET). The tumor cells were all cultivated for at least 10 passages. We used phase contrast, confocal microscopy, and immunohistochemistry to investigate spheroids and monolayer cultures. The supernatants of tumor cells grown in 2D and 3D cultures were studied using ELISA and multiplex analysis for the production of a spectrum of chemokines and cytokines supporting the immunosuppression, invasion and metastasis processes. Results Tumor specimens received were predominantly of metastatic origin (75%). In 100% of cases 2D cultures were received, in 88.6% of cases (39 out of 44) we succeeded in obtaining spheroids. There was no direct correlation between the efficiency of tumoroid formation and the tumor's histogenetic origin and the stage of the cancer process (primary tumor, recurrence, metastasis). The median size of spheroids by 4-5 days of cultivation with a starting concentration of 10000 cells per well was 657.14 μm for melanoma (min 400 - max 1000 μm), 571.42 μm (min 400 - max 700 μm), 507.14 μm (min 300 - max 600 μm) for soft tissue sarcomas, 650.0 μm (min 400 - max 900 μm) for osteogenic sarcomas. Immunochemical analysis of Ki-67, GLUT1, and Ecadherin markers was carried out for tumor tissue samples, single-layer tumor cultures, and tumoroids of every patient. The distribution of the stained groups in the spheroids was distinct from the monolayer cultures and more in accordance with the distribution of such in the tissue tumor, the number of Ki-67+ cells was increasing in the spheroids. We detected no dependence of Ki-67+ and GLUT1+ cell localization grade on spheroid size. We identified E-cadherin in tumor tissue and tumoroids of breast carcinoma and one melanoma culture. Monolayer cultures did not express it. The increase in secretory cell activity of the solid tumor cells from 2D to 3D system was observed when CCL2, CCL3, CXCL1, CXCL16, MIF, IL10, MICA (p<0.01) were investigated. Conclusion The presence of patient-specific cells of solid tumors in a 3D environment causes activation of the proliferative and metabolic processes as compared to monolayer cultures, which makes these models approximate the real world clinical picture. The production of chemokines that can attract to the tumor various types of immune system cells, to include their immature versions, as well as production of cytokines and Immunosuppression factors that, when present in the tumor microenvironment in the high concentrations, contribute to the formation of immune cells having suppressive capacities occurs in the 3D cell system. Three-dimensional model of the initial tumor nodule formation stage thus demonstrates the forming process of tumor cells favorable for them microenvironment. Construction of three-dimensional models - spheroids of tumor cells of differing histogenesis demands individual approach and more thorough investigation.
Feb 2021 DOI 10.14302/issn.2372-6601.jhor-21-3733
Breast implant-associated anaplastic large cell lymphoma (ALCL) is a recently recognized type of T-cell lymphoma that can develop following breast implants, with morphologic and immunophenotypic features indistinguishable from those of ALK-negative ALCL. Here we report a case of a 58-year-old woman with a history of subglandular silicone implants placed for bilateral breast augmentation 25 years ago, who presented with bilateral breast pain and was found to have bilateral Baker Grade III capsular contracture, and heterogenous fluid collection centered near the left third costochondral articulation, a suspicious left chest wall lesion, and left axillary lymphadenopathy on imaging. A left axillary lymph node core biopsy and an aspiration of the fluid were performed, and no malignant cells were identified. The patient underwent bilateral removal of breast implants and total capsulectomies. Microscopic examination of the capsule surrounding the left breast implant revealed large pleomorphic tumor cells in a fibrinous exudate. By immunohistochemistry, the tumor cells were found to be positive for CD3 (subset), CD4, CD7, CD30 (strong and uniform), and CD43, and negative for CD2, CD5, CD8, and ALK1, supporting the diagnosis of breast implant-associated ALCL. No lymphoma cells were identified in the right breast capsule, confirmed by CD30 stain. Breast implant-associated ALCL is a very rare disease that can develop many years after breast implant placement. Proper evaluation with breast imaging and pathologic workup is essential to confirm the diagnosis in suspected cases. Our case highlights that adequate sampling is important in the investigation of patients with suspected breast implant-associated ALCL.
Sep 2020 DOI 10.14302/issn.2372-6601.jhor-20-3552
Plasma cell neoplasms of the thyroid gland are uncommon. They may occur either as a primary extraosseous (extramedullary) plasmacytoma or as secondary involvement by multiple myeloma (MM). Here, we report the case of a 62-year-old female, presenting with goiter and Hashimoto’s thyroiditis, in whom the histologic diagnosis of extraosseous plasmacytoma was unexpected. Histology of the total thyroidectomy specimen showed a diffuse infiltration of well-differentiated plasma cells against a background of Hashimoto’s thyroiditis. By immunohistochemistry, the majority of the plasma cells are positive for IgG heavy chain and kappa light chain (kappa:lambda ratio was about 6-7:1). PCR analysis of the immunoglobulin heavy and kappa chain (IGH, IGK) gene rearrangements showed clonal IGH and IGK gene rearrangements. MM was ruled out by lack of MM-related end organ damage and negative serum protein electrophoresis, immunofixation, and bone marrow biopsy. Although rare, plasmacytoma should be considered in patients presenting with enlarging thyroid gland and autoimmune thyroiditis. Histologic diagnosis and differential diagnoses are comprehensively discussed.
Dec 2019 DOI 10.14302/issn.2575-1212.jvhc-19-3101
Papillary carcinoma is a mammary neoplasia of women and female dogs characterized by papillary fibrovascular projections lined by epithelial cells. Evaluation on the biology of these tumors can be done by immunohistochemistry through detection of alpha-smooth muscle actin protein in the papillary myoepithelium, which lacks such a molecule during malignant proliferations. Thus, this study aimed at determining the malignancy degree of papillary mammary tumors of female dogs by immunohistochemistry. Twenty samples of mammary neoplastic tissues collected from female dogs treated in the Veterinary Hospital at FCAV were evaluated by Hematoxylin and Eosin staining (H&E) and tumor cells were immunolabelled with monoclonal antibody to alpha-smooth muscle actin (α-SMA). Five out of 20 cases showed positive immunolabeling greater than 10% of the total immunolabeling. The remaining fourteen cases presented immunostaining lesser than 10% showing decrease or absence of α-SMA labeling in the myoepithelium of the papilla tumors. All those cases in which immunostained cell was over 10% of the neoplasm (5 immunostains of 20 total cases) were classified as benign whereas those below 10% of immunostained in the slid were considered as malignant. Therefore, immunohistochemistry played an essential role in differentiating benign and malignant papillary tumors of bitches as already described for female. Tumor classification by conventional methods, such as H&E staining, can lead to erroneous interpretations on the real biological behavior of the papillary mammary tumor.
Aug 2018 DOI 10.14302/issn.2641-9181.ijnr-18-2195
Objectives: An association between the measles virus and Hodgkin lymphoma has been disclosed by our laboratory in Beer-Sheva, starting in 2003. We question the refutation of our study and the absence of interest among experts. Methodology: It was based on immunohistochemistry with commercial, as well as experimental anti-measles antibodies. It relied also on RT-PCR and in situ hybridization evidence of measles virus RNA. Key Results: At this stage (2004), the link between the virus and the lymphoma was essentially descriptive. The first and last response to our challenge appeared in 2007, in the form of doublet articles, in the same issue of a major cancer journal. The two European research groups responding, rejected categorically our findings by proposing different arguments. Major Conclusion: As reservations to these reactions became soon apparent, a series of papers from our laboratory were published. These articles concerned the evidence of a relationship between the measles virus and additional categories of cancers. Different malignancies in which this virus was not expressed at all, were also described. A further study suggested a mechanism by which the measles virus may activate lymphomagenesis in classic Hodgkin lymphoma. To our dismay, and in spite of repeated calls to verify the various results, no further response was obtained from international experts.
Jan 2018 DOI 10.14302/issn.2578-8590.ipj-17-1910
Following ocular trauma and retinal detachment, gliotic changes in the retina may develop over the subsequent month, a process known as PVR (proliferative vitreoretinopathy). There have been no successful therapeutic interventions to inhibit PVR. The protein CTGF (Connective Tissue Growth Factor) has been associated with retinal PVR and other fibrotic diseases of the retina in clinical studies but the mechanistic link between different pathologies and retinal gliosis has not been determined. In addition, CTGF has been previously noted to be associated, in some cases, with YAP/TAZ (Yes-associated protein and Tafazzin protein complex), transcriptional regulatory proteins that change subcellular localization in response to mechanical cues, such as the stiffness of the underlying material. We have previously shown that the mRNA for CTGF is markedly (100-fold) upregulated in retinal Müller cells grown on soft substrates. In order to evaluate if the mechanism by which mechanotransduction modulating CTGF production in retinal Müller cells involves the YAP/TAZ complex, this study tests the influence of substrate stiffness on the time dependence of CTGF protein expression, as well as subcellular localization of YAP/TAZ using a conditionally-immortalized mouse retinal Müller cell line plated on laminin-coated, polyacrylamide substrates of varying elastic modulus. Changes were assayed using immunohistochemistry and ELISA (Enzyme-Linked ImmunoSorbent Assay). In retinal Müller cells, the relationship between elastic modulus and the pattern of CTGF protein expression was bimodal, with CTGF levels rising more rapidly for cells on hard substrates and more slowly for cells grown on soft substrates. In addition, nuclear localization of YAP/TAZ corresponded directly to the maximum CTGF expression.
Dec 2017 DOI 10.14302/issn.2576-6694.jbbs-17-1869
Introduction Bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, infectious and neoplastic disease, characterized by the presence of multiple papillomas that can regress spontaneously or to persist and progress to malignancies when in association with environmental cofactors. Although recognized that the BPV can induce DNA damages, the viral role following cancer initiation remains unresolved. Based on this, we stablished cell lines derived from cutaneous papilloma, fibropapilloma and esophageal carcinoma to study the BPV action on epithelial-mesenchymal transition (EMT). Our results showed strong evidences that the virus action can contribute to EMT and, therefore, metastasis. Aim In this study, we analyzed the expression levels of the EMT markers (cytokeratin 10, STAT3 Y705, Oct-3/4 and vimentin) in paraffin-embed samples, using the same tissues that originated the cell lines previous studied, aiming to validate the results observed using cell lines. Material and Methods Expression levels of these markers was analyzed by immunohistochemistry and the collagen composision by Picrosirius red staining. Results We verified an overexpression of these markers in fibroblastoid cells present into the epidermis and ketarinocyte-like cells into the dermis present in dermo-epidermal junction. These data reinforce our previous results using cell cultures, validating both systems (cell culture and paraffin-embed tissues) as useful models to study the natural history of BPV-infected lesions. Conclusion Altogether, the results from these systems indicate that the BPV promote the cancer progression and metastasis through the transdifferentiation of an epithelial to mesenchymal cells (EMT).
Jul 2017 DOI 10.14302/issn.2575-1212.jvhc-17-1586
The mammary tumor is one of the most common cancer in female dogs and, at the present days, there is a big focus on the study of the relation between this kind of tumor in animals and the cells that stay around them, like the inflammatory cells. The objective of this study was to evaluate and show where the inflammatory cells stay in simple mammary carcinomas in female dogs by immunohistochemistry. Samples of simple mammary carcinomas (tumor group; n=26) and mammary gland samples without tumor (control group; n=18) were submitted to immunohistochemical analysis for the detection of T lymphocytes, macrophages, plasma cells and the MHC-II molecule. The mast cells were evaluated by the histochemical technique (toluidine blue). Lymphocytes, macrophages and mast cells were observed distributed in the tumor stroma. MHC-II was detected in tumor cells and in the inflammatory infiltrate. Plasma cells predominated in the peritumoral stroma. Macrophages differed significantly between the two groups and predominated in the tumor group. In the comparison between histological types of mammary carcinomas, mast cells differed significantly between solid tumors of the tubular / papillary types. The cytoplasmic immunodetection of MHC-II was suggested an inefficient antigen presentation. Some of the leukocytes present in the tumor infiltrate, appear to be exerting a pro-tumor effect and allowing the progression of tubular and papillary carcinomas. But in solid carcinomas (may be poorly immunogenic), as they had the lowest proportion of leukocytes present in the tumor site. More studies are necessary to confirm these results, such as the determination of the cytokine profile and the predominant leukocyte subpopulations in the tumor microenvironment.
Feb 2017 DOI 10.14302/issn.2372-6601.jhor-17-1423
Background: The diagnosis and treatment outcomes of Non- Hodgkin Lymphoma’s (NHL) in resource poor countries in the absence of routine molecular studies and immunohistochemistry is challenging. Methods: A retrospective review of case folders of NHL patients aged13 years and above. Information obtained from the case folders included age, sex, histological subtype, subtypes using the Working Formulation and WHO classifications. Treatment given and follow up information were also evaluated. Results: A total of 279 cases of NHL were identified within the study period. The mean age of the patients was 48.8 ± 17.0 years. The male to female ratio was approximately 1.5:1. The majority of cases seen (53%) were diffuse large B- cell lymphoma. Chronic lymphocytic leukaemia/ small lymphocytic lymphoma (22.2%) was the next most common subtype. Other sub types seen, in order of frequency, included diffuse mixed cell lymphoma (6.4%), gastric lymphomas (3.9%), mediastinal B- cell lymphoma (2.9%), Burkitt’s lymphoma (1.8%), splenic marginal zone B-cell lymphoma (1.1%), lymphoblastic lymphoma (1.1%), mucosa- associated lymphoid tissue (MALT) type B- cell lymphoma (0.7%) and follicular lymphoma (0.7%). Conclusion: This study provides an overview of the distribution of NHL subtypes and their outcomes in a resource constrained setting. Immunohistochemistry, cytogenetics and specific molecular studies which are important in characterization of NHLs, should be made affordable and accessible in low income countries.
May 2014 DOI 10.14302/issn.2572-3030.jcgb-13-369
Insulin receptor substrate (IRS) 1 and 2 are downstream signaling proteins that influence breast pathophysiology. IRS-1 promotes carcinoma cell proliferation; whereas IRS-2 regulates cell motility, invasion, and glycolysis. Our lab has shown that distinct cellular localization of IRS-2 also plays a role in carcinoma cell function. Oncotype DX (Genomic Health) (ODX) is a 21-gene expression profile used to classify carcinomas with low, intermediate, and high risk recurrence scores (RS). Our aim is to correlate expression and cellular localization of IRS proteins in breast carcinomas with their ODX RS. 97 breast carcinomas sent for ODX testing from 2006-2009 were collected and grouped according to their RS (low, intermediate or high). Immunohistochemistry for IRS-1/-2 was performed. Specific criteria were used to evaluate IRS staining patterns. Follow-up data, ranging from 3-6 years, was available. Statistical analysis was performed to correlate staining patterns of IRS-1/-2 with the three RS groups. IRS-1 staining, predominantly nuclear, did not significantly correlate with RS (P=.5645). IRS-2 expression patterns did show statistical significance amongst the three RS groups (P=.0371). Tumors with intermediate and low RS were more likely to exhibit punctate and diffuse cytoplasmic expression of IRS-2, and cell membrane expression was uncommon in this group. Expression and cellular localization of IRS proteins play an important role in breast cancer cell biology, and expression patterns for IRS-2 do demonstrate a significant correlation with ODX RS. Further studies are required to elucidate the significance of cellular localization of IRS-1/-2 proteins in breast carcinoma cells and their relationship to ODX scores.
Jan 2013 DOI 10.14302/issn.2329-9487.jhc-12-102
Background: Heart valves share developmental signaling pathways with cartilage and bone. While calcific aortic valve disease (CAVD) has been associated with valve calcification and stenosis, suggestive of osteogenesis, myxomatous mitral valve disease (MMVD) is characterized by net matrix degradation, exuberant deposition of proteoglycan, and valve regurgitation. Methods: We determined the presence of cartilage-abundant proteoglycan, aggrecan; cartilage-specific type II collagen; chondrogenic transcription factor, Sox9; and osteogenic transcription factor, Runx2 in human normal and myxomatous mitral valve leaflets by immunohistochemistry. Results and Conclusions: Myxomatous, but not normal, mitral valves demonstrated sharp focal areas that were abundant in aggrecan, type II collagen, and Sox9. These focal areas co-localized with areas of myxomatous pathologic change on Movat staining. Some cells in these areas had a round and hypertrophic morphology reminiscent of chondrocytes. Runx2 was only weakly present in normal and myxomatous mitral valves. These findings suggest a focal pathologic process in MMVD that mimics chondrogenesis.