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Introduction. Interstitial Cells of Cajal (ICCs) play a critical role in the regulation of gastrointestinal motility and have been implicated in various functional gastrointestinal disorders. Recent research indicates a possible association between ICCs and the tumor risk of Gastrointestinal Stromal Tumors (GISTs). This research aims to examine the clinical, histopathological, and biomolecular characteristics of ICCs and their relevance in assessing GIST risk. Materials and Methods. This study examined fourteen GIST patients who underwent surgical intervention at the Surgery Department of Carol Davila Nephrology Hospital in Bucharest. Parameters including age, gender, tumor location/ dimensions were scrutinized. Immunohistochemistry employing markers CD117, DOG-1, and CD34 was employed to ascertain the presence of ICCs and GISTs. Results. The GIST risk stratification revealed distribution with 35.71% very low-risk, 21.42% low-risk, 14.28% intermediate-risk, and 28.57% high-risk categories. Predominantly, 57.14% of cases fell within the very low-risk and low-risk categories. Positive immunoreactivity for CD117 and DOG-1 was noted in 92.86% of patients, while CD34 exhibited positivity in 85.71% of cases. Gastric GISTs manifested heightened marker expression. Notably, immunohistochemistry unveiled robust positivity for CD117, DOG-1, and CD34, illustrating a positive correlation between elevated ICC levels and high-risk GISTs. Conclusions. The findings propose an association between ICC levels and high-risk GISTs, accentuating the diagnostic utility of CD117, DOG-1, and CD34 markers in GIST assessment.

Abstract Introduction Hirschsprung’s disease (HD) is a neurogenic intestinal disorder attributed to incomplete neural crest cell migration during fetal intestinal development, leading to an aganglionic segment of the colon and functional obstruction. Associated malformations like intestinal atresia, hydronephrosis, and imperforate anus can accompany Hirschsprung’s disease. this study aims to evaluate the efficacy of Calretinin and Cajal cells (CD34 and CD117) immunohistochemical staining in improving HD diagnosis. Methods The study involved 70 pediatric patients suspected of Hirschsprung’s disease. Clinical, histopathological, and immunohistochemical analyses were conducted, focusing on calretinin, CD34, and CD117 markers to identify ganglion cells and Cajal cells. Data were statistically analyzed using SPSS software. Results In the examination of the samples, the calretinin marker exhibited a consistent accuracy of 100% in diagnosing Hirschsprung’s disease (with sensitivity and specificity both at 100%). Regarding the markers for Cajal cells in cases of Hirschsprung’s disease, an irregularity in the arrangement of Cajal cells was observed, which was absent in normal cases. These markers also demonstrated a specificity and sensitivity of 100% in diagnosing the disease. Conclusion Hirschsprung’s disease remains a complex condition with multifaceted pathophysiological mechanisms. Calretinin immunohistochemical staining offers enhanced diagnostic accuracy, while the debate surrounding ICC distribution underscores the need for advanced diagnostic techniques. Further research is warranted to unravel the intricacies of Hirschsprung’s disease and its associated complications.

Abstract The current investigation aims to study the embryonic dermis formed in the early stages of development and identify the initial interstitial components of the dermis that serve as biological and structural scaffolds for the development of the dermal tissue. To investigate the dermal structure, the current study used morphological and immunological techniques. TCs identified by TEM. They had a cell body and unique podomeres and podoms. They formed a 3D network spread throughout the dermis. Homocellular contact established between them, as well as heterocellular contacts with other cells. Immunohistochemical techniques using specific markers for TCss CD34, CD117, and VEGF confirmed TC identification. TCs represent the major interstitial component in the dermal tissue. They established a 3D network, enclosing other cells and structures. Expression of VEGF by TC promotes angiogenesis. TCs establish cellular contact with sprouting endothelial cells. At the site of cell junction with TCs, cytoskeletal filaments identified and observed to form the pseudopodium core that projects from endothelial cells. TCs had proteolytic properties that expressed MMP-9, CD68, and CD21. Proteolytic activity aids in the removal of components of the extracellular matrix and the phagocytosis of degraded remnants to create spaces to facilitate the development of new dermal structures. In conclusion, TCs organized the scaffold for the development of future dermal structures, including fibrous components and skin appendages. Studying dermal TCs would be interested in the possibility of developing therapeutic strategies for treating different skin disorders and diseases.

Clear cell hidradenoma is a rare benign tumor of the breast, its origin and pathogenesis are controversial. We have experienced a case of breast clear cell hidradenoma with mastermind like transcriptional coactivator 2 (MAML2) gene rearrangement. The patient found a painless mass with a hard texture in the left breast areola without nipple discharge. Microscopically, the tumor was cystic and solid, locally arranged in a glandular structure, covered by single cuboidal cells; it was composed of clear cells, epidermoid cells, and basaloid cells; there were no necrosis or mitotic figures. Immunohistochemical staining showed that the tumor cells positively expressed low‐molecular cytokeratin 7, low‐molecular cytokeratins (Cam5.2), high‐molecular cytokeratin 5/6, cytokeratin 14, CD117, and p63; and did not express calponin, and smooth muscle myosin heavy chain. The cuboidal cells were positive for SOX10 but negative for p63. Additionally, periodic acid‐Schiff reaction showed purple‐red granules in the tumor cytoplasm, but Alcian blue staining showed no blue mucus in the cytoplasm. The split signals of MAML2 gene were detected by fluorescence in situ hybridization. Subtle histological and immunophenotypical differences may help to distinguish breast clear cell hidradenoma from common breast tumors. Furthermore, the MAML2 gene rearrangement may be a molecular genetic characteristic of breast clear cell hidradenoma. [ABSTRACT FROM AUTHOR]

Introduction. Interstitial Cells of Cajal (ICCs) play a critical role in the regulation of gastrointestinal motility and have been implicated in various functional gastrointestinal disorders. Recent research indicates a possible association between ICCs and the tumor risk of Gastrointestinal Stromal Tumors (GISTs). This research aims to examine the clinical, histopathological, and biomolecular characteristics of ICCs and their relevance in assessing GIST risk. Materials and Methods. This study examined fourteen GIST patients who underwent surgical intervention at the Surgery Department of Carol Davila Nephrology Hospital in Bucharest. Parameters including age, gender, tumor location/ dimensions were scrutinized. Immunohistochemistry employing markers CD117, DOG-1, and CD34 was employed to ascertain the presence of ICCs and GISTs. Results. The GIST risk stratification revealed distribution with 35.71% very low-risk, 21.42% low-risk, 14.28% intermediate-risk, and 28.57% high-risk categories. Predominantly, 57.14% of cases fell within the very low-risk and low-risk categories. Positive immunoreactivity for CD117 and DOG-1 was noted in 92.86% of patients, while CD34 exhibited positivity in 85.71% of cases. Gastric GISTs manifested heightened marker expression. Notably, immunohistochemistry unveiled robust positivity for CD117, DOG-1, and CD34, illustrating a positive correlation between elevated ICC levels and high-risk GISTs. Conclusions. The findings propose an association between ICC levels and high-risk GISTs, accentuating the diagnostic utility of CD117, DOG-1, and CD34 markers in GIST assessment. [ABSTRACT FROM AUTHOR]

Canine ovarian cancer poses a significant diagnostic and therapeutic challenge. The heterogeneous nature of ovarian tumours makes accurate histological identification difficult, whilst treatment is limited to surgical excision. The tyrosine kinase receptor CD117 is neo-expressed in many tumours and represents a potential diagnostic and prognostic biomarker and therapeutic target. This study aimed to establish if CD117 is neoexpressed in canine ovarian tumours. Immunohistochemistry was employed to assess expression of CD117 in 29 canine ovarian tumour samples. CD117 labelling was assessed with a semiquantitative immunoreactivity score, and the location of labelling was recorded as membranous, focal cytoplasmic or diffuse cytoplasmic. Histological morphology was assessed and used to assign subgroups based on growth pattern. Cytokeratin 7 labelling was used to indicate the tumour type as epithelial or sex-cord stromal in origin. Mitotic index, percentage of necrosis and vascular invasion were also assessed and evaluated for association with CD117 expression. Overall, 81% of ovarian tumours neoexpressed CD117 and normal ovarian tissue did not express CD117. Positive immunolabelling was seen in a subset of cells in both ovarian carcinomas (n = 20) and ovarian granulosa cell tumours (n = 3). There was no association between CD117 expression and patient age, histological subtype, mitotic index, percentage of necrosis or vascular invasion. This is the largest study to identify the expression of CD117 in canine ovarian tumours, but further research is needed to elucidate its prognostic and therapeutic value. [ABSTRACT FROM AUTHOR]

The current investigation aims to study the embryonic dermis formed in the early stages of development and identify the initial interstitial components of the dermis that serve as biological and structural scaffolds for the development of the dermal tissue. To investigate the dermal structure, the current study used morphological and immunological techniques. TCs identified by TEM. They had a cell body and unique podomeres and podoms. They formed a 3D network spread throughout the dermis. Homocellular contact established between them, as well as heterocellular contacts with other cells. Immunohistochemical techniques using specific markers for TCss CD34, CD117, and VEGF confirmed TC identification. TCs represent the major interstitial component in the dermal tissue. They established a 3D network, enclosing other cells and structures. Expression of VEGF by TC promotes angiogenesis. TCs establish cellular contact with sprouting endothelial cells. At the site of cell junction with TCs, cytoskeletal filaments identified and observed to form the pseudopodium core that projects from endothelial cells. TCs had proteolytic properties that expressed MMP-9, CD68, and CD21. Proteolytic activity aids in the removal of components of the extracellular matrix and the phagocytosis of degraded remnants to create spaces to facilitate the development of new dermal structures. In conclusion, TCs organized the scaffold for the development of future dermal structures, including fibrous components and skin appendages. Studying dermal TCs would be interested in the possibility of developing therapeutic strategies for treating different skin disorders and diseases. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the expression of CD117 and DOG1 in triple-negative breast cancer (TNBC) and to explore their relationship with clinicopathologic features and prognosis.MethodsThe patients with TNBC in Peking Union Medical College Hospital from 2000 to 2011 were retrospectively collected and tissue microarrays were made. The expression of CD117 and DOG1 in tumor cells was detected by immunohistochemistry to analyze their relationship with the clinicopathological characteristics of the patients, such as age, tumor diameter, American Joint Committee on Cancer (AJCC) cancer stage, histological grade, P53, and Ki-67 proliferation index, and explore the effect of both on the survival of patients.ResultsA total of 185 TNBC patients meeting the inclusion and exclusion criteria were selected, of which 24 (12.97%) were CD117 positive and 22 (11.89%) were DOG1 positive, with a co-expression rate of 1.62%. Compared with CD117-negative patients, CD117-positive patients had higher Ki-67 proliferation index (87.50% vs. 67.70%, P=0.048), basal-like TNBC (95.83% vs. 74.53%, P=0.020), and P53 diffuse positive (33.33% vs. 13.66%, P=0.032).Compared with DOG1-negative patients, DOG1-positive patients had lower proportions of tumor diameter ≤2 cm (22.73% vs. 45.40%, P=0.026) and basal-like TNBC (54.55% vs. 80.37%, P=0.015). The median follow-up was 71 months (range: 2-170 months), 4 cases (2.16%) were lost to follow-up, 66 cases (35.68%) relapsed or had distant metastasis, and 34 cases (18.38%) died. Survival analysis showed that AJCC stage (HR=7.624, 95% CI: 2.187-26.576, P=0.001) and CD117 positive with P53 diffuse strong positive (HR=3.942, 95% CI: 1.366-11.379, P=0.011) were negatively correlated with the overall survival of TNBC patients.ConclusionsThe expression of CD117 and DOG1 were significantly related to basal-like TNBC, CD117 positive with P53 diffuse strong positive may be correlated with a shorter overall survival and a higher mortality risk.

Abstract Background Mast cells have been implicated in the pathology of various urinary bladder disorders. However, the distribution of mast cells throughout urinary bladder tissue remains uncertain despite mast cell prevalence being relatively well-defined. Using a mouse tissue model, this study aims to characterise the prevalence and distribution of mast cells throughout the urinary bladder. Methods Bladder tissues were collected from six C57BL/6J female mice. Mast cell prevalence was quantified by flow cytometry, based on the expression of the following characteristic markers: CD45, CD117 and FcɛRIα. The toluidine blue stain assessed mast cell distribution, size, and proximity to vasculature. A repeated measures one-way ANOVA was used to evaluate the density of mast cells between the discrete layers of the urinary bladder, and an ordinary one-way ANOVA was used to assess potential differences between mast cell size across the urinary bladder wall. Results It was determined that mast cells compose less than 4% of all live leukocytes in the urinary bladder. They were also found to be more prominent in the lamina propria and detrusor muscle layers, compared to the urothelium and adventitia. In addition, 20.89% of mast cells were located near vasculature, which may be an important factor in consideration of their function and potential to contribute to various bladder pathologies, such as cystitis or overactive bladder. Conclusion These findings provide a baseline understanding of mast cell prevalence and distribution throughout the urinary bladder.

Mast cell tumor (MCT) is a common skin cancer in dogs that has a wide range of clinical behaviors. The purpose of this study was to develop a novel multicolor flow cytometry (FC) panel that will enable the quantification of candidate prognostic markers (Ki-67 and pKIT) in fine needle aspirate (FNA) samples prior to surgical removal of the tumors. FNA of canine MCTs and the NI-1 cell line were utilized to develop a FC panel that includes a viability dye (FVS620, BD Biosciences; 7-AAD, Invitrogen) and the following primary conjugated antibodies: CD117-PE (ACK45, BD Biosciences), pKIT-A647 (polyclonal bs-3242R, BIOSS) and Ki-67-FITC (20Raj1, eBioscience; MIB-1, DAKO). A total of nine FNA samples of canine MCTs were collected, seven out which produced sufficient cells for FC analysis. The Ki-67 antibody clone 20Raj1 produced a positive signal when applied to blood leukocytes but failed to provide robust labeling of neoplastic mast cells. The Ki-67 antibody clone MIB-1 delivered a superior staining quality in both the NI-1 cells and primary MCT cells. CD117-PE signal was adequate post fixation and permeabilization and in the combination of 7-AAD. pKIT produced non-specific staining and was not suitable for this multicolor FC panel. In conclusion, FNA samples of canine MCTs can often yield adequate cell numbers for FC analysis, and a multicolor FC panel was developed that can detect Ki-67 in canine mast cells. This would permit further studies into the potential use of this panel for canine cutaneous and subcutaneous MCT prognostication purposes.

Background: Neuroproliferative vestibulodynia (NPV), a provoked genital pain characterized by severe allodynia and hyperalgesia, is confirmed in excised vestibular tissue by immunohistochemical staining (>8 CD117-positive immunostained cells/100× microscopic field) rather than by hematoxylin and eosin staining. Aim: In this study we sought to assess immunostaining of tissue samples obtained during vestibulectomy surgery and to correlate results with patient outcomes. Methods: Patients (n = 65) meeting criteria for NPV who underwent vestibulectomy during the period from June 2019 through December 2022 formed the study cohort. We performed assessment of pathology of vestibular tissues by use of immunohistochemical staining, including quantitation of mast cells by CD117 (mast cell marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. Outcomes: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. Results: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. Outcomes: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. Results: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the median area of CD117 immunostaining was similar in both regions (0.69% and 0.73%). The median area of PGP9.5 immunostaining was 0.47% and 0.31% in these same regions. Pain scores determined with cotton-tipped swab testing were nominally higher in lifelong vs acquired NPV patients, reaching statistical significance in the 1:00-11:00 o'clock region (P <.001). The median score for the McGill Pain Questionnaire affective subscale dimension was also significantly higher in lifelong vs acquired NPV patients (P =.011). No correlations were observed between hematoxylin and eosin results and density of mast cells or neuronal markers. Of note, 63% of the patient cohort reported having additional conditions associated with aberrant mast cell activity. Clinical Implications: The pathology of NPV is primarily localized to the vestibular epithelial basement membrane and subepithelial stroma with no visible vulvoscopic findings, making clinical diagnosis challenging. Strengths and Limitations: Strengths of this study include the large number of tissues examined with what is to our knowledge the first-ever assessment of the 12:00 vestibule. Major limitations are specimens from a single timepoint within the disease state and lack of control tissues. Conclusions: Performing immunohistochemical staining of excised vestibular tissue with CD117 and PGP9.5 led to histometric confirmation of NPV, indications that NPV is a field disease involving all vestibular regions, validation for patients whose pain had been ignored and who had experienced negative psychosocial impact, and appreciation that such staining can advance knowledge. [ABSTRACT FROM AUTHOR]

Simple Summary: In this manuscript, the characteristics of cancer stem cells and their potential role in endometrial cancer are explored. An understanding of the mechanisms behind cancer stem cells in endometrial cancer is crucial because these cells potentially play a key role in how the cancer grows and spreads. The authors aim to review the most recent data concerning cancer stem cells in endometrial cancer, especially biomarkers which could enable identification and prognosis. The determination of signalling pathways crucial for the functioning of cancer stem cells could help with the design of effective treatment strategies. Endometrial cancer is one of most common types of gynaecological tumours in developing countries. It has been suggested that cancer stem cells play an important role in the development of endometrial cancer. These are a subset of highly tumorigenic cells with similar features to normal stem cells (unlimited proliferation, multi-potential differentiation, self-renewal, aggressiveness, invasion, recurrence, and chemo- and endocrine therapy resistance). Wnt/β-catenin, Hedghog, and Notch1 are the most frequently activated pathways in endometrial cancer stem cells. The presence of cancer stem cells is associated with the resistance to chemotherapy caused by different mechanisms. Various markers, including CD24, CD40, CD44, CD9, CD133, and CD 166, have been identified on the surface of these cells. A higher expression of such markers translates into enhanced tumorigenicity. However, there is no strong evidence showing that any of these identified markers can be used as the universal marker for endometrial cancer stem cells. Growing data from genomic and proteomic profiling shed some light on the understanding of the molecular basis of cancers in humans and the role of cancer stem cells. However, there is much left to discover. Therefore, more studies are needed to fully uncover their functional mechanisms in order to prevent the development and recurrence of cancer, as well as to enhance treatment effectiveness. [ABSTRACT FROM AUTHOR]

Background Mast cells have been implicated in the pathology of various urinary bladder disorders. However, the distribution of mast cells throughout urinary bladder tissue remains uncertain despite mast cell prevalence being relatively well-defined. Using a mouse tissue model, this study aims to characterise the prevalence and distribution of mast cells throughout the urinary bladder. Methods Bladder tissues were collected from six C57BL/6J female mice. Mast cell prevalence was quantified by flow cytometry, based on the expression of the following characteristic markers: CD45, CD117 and FcɛRIα. The toluidine blue stain assessed mast cell distribution, size, and proximity to vasculature. A repeated measures one-way ANOVA was used to evaluate the density of mast cells between the discrete layers of the urinary bladder, and an ordinary one-way ANOVA was used to assess potential differences between mast cell size across the urinary bladder wall. Results It was determined that mast cells compose less than 4% of all live leukocytes in the urinary bladder. They were also found to be more prominent in the lamina propria and detrusor muscle layers, compared to the urothelium and adventitia. In addition, 20.89% of mast cells were located near vasculature, which may be an important factor in consideration of their function and potential to contribute to various bladder pathologies, such as cystitis or overactive bladder. Conclusion These findings provide a baseline understanding of mast cell prevalence and distribution throughout the urinary bladder [ABSTRACT FROM AUTHOR]

Introduction: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors that can arise anywhere within the gastrointestinal tract. Approximately 70 % are in the Stomach, representing 1 – 3 % of all gastrointestinal malign neoplasms. GISTs originate from the Cajal interstitial cells or their stem cell precursors within the myenteric plexus of the muscularis propria. Histologically, GIST presents three different architectural patterns: a. composed of epitheloid cells embedded in a thin reticular stroma; b. by spindle cells with a fascicular or storiform arrangement immersed in a thin reticular stroma focally myxoid, and c. the mixed forme. This study describes a 72-year-old man who, in the computed tomography, presented a gross appearance as pancreatic cystic neoplasia. Clinicians should be aware that this condition might be mistaken for a primary pancreatic malignancy. The diagnostic Workup includes endoscopy with ultrasonography, cross-sectional imaging studies, and histopathological examination. Conclusions: The reported case illustrates that the retroperitoneum might be the place of initial presentation of a cystic gastric GIST and that only an accurate pathological evaluation can establish the diagnosis and origin. Clinicians must know this condition might be mistaken for a primary pancreatic malignancy. Early surgical resection is the gold standard of treatment for primary GIST.

This case report details a rare instance of a perforated jejunal gastrointestinal stromal tumor (GIST) in a 76-year-old female patient. The patient presented with acute abdominal pain and distension without any changes in bowel habits or episodes of nausea and vomiting. Initial diagnostics, including abdominal plain radiography and ultrasonography, were inconclusive; however, a computed tomography (CT) scan revealed pneumoperitoneum and an irregular fluid collection suggestive of small intestine perforations. Surgical intervention uncovered a 35 mm jejunal GIST with a 10 mm perforation. Histopathological examination confirmed a mixed cell type GIST with high malignancy potential, further substantiated by immunohistochemistry markers CD117, DOG1, and vimentin. Molecular analysis illuminated the role of key oncogenes, primarily KIT and PDGFRA mutations, emphasizing the importance of molecular diagnostics in GIST management. Despite the severity of the presentation, the patient’s postoperative recovery was favorable, highlighting the effectiveness of prompt surgical and multidisciplinary approaches in managing complex GIST cases.

Simple Summary: This manuscript focuses on cancer stem cells and the diagnostic potential of selected biomarkers of these cells in ovarian cancers. Ovarian cancer has nonspecific clinical symptoms. Also, there are no reliable diagnostic and prognostic biomarkers. For these reasons, nearly 70% of patients are diagnosed with ovarian cancer at the metastatic stage. The role of CSCs in ovarian cancer initiation and progression and their impact on resistance to therapy are still the subjects of many studies; however, the results are sometimes conflicting due to the heterogeneity and plasticity of CSCs. The identification of CSC phenotypes could contribute to the development of more effective diagnostic and therapeutic strategies in ovarian cancer. This is especially important since strategies to overcome resistance to conventional treatments and prolong patient survival are highly awaited. Ovarian cancer is the most lethal gynaecological cancer and the eighth most common female cancer. The early diagnosis of ovarian cancer remains a clinical problem despite the significant development of technology. Nearly 70% of patients with ovarian cancer are diagnosed with stages III–IV metastatic disease. Reliable diagnostic and prognostic biomarkers are currently lacking. Ovarian cancer recurrence and resistance to chemotherapy pose vital problems and translate into poor outcomes. Cancer stem cells appear to be responsible for tumour recurrence resulting from chemotherapeutic resistance. These cells are also crucial for tumour initiation due to the ability to self-renew, differentiate, avoid immune destruction, and promote inflammation and angiogenesis. Studies have confirmed an association between CSC occurrence and resistance to chemotherapy, subsequent metastases, and cancer relapses. Therefore, the elimination of CSCs appears important for overcoming drug resistance and improving prognoses. This review focuses on the expression of selected ovarian CSC markers, including CD133, CD44, CD24, CD117, and aldehyde dehydrogenase 1, which show potential prognostic significance. Some markers expressed on the surface of CSCs correlate with clinical features and can be used for the diagnosis and prognosis of ovarian cancer. However, due to the heterogeneity and plasticity of CSCs, the determination of specific CSC phenotypes is difficult. [ABSTRACT FROM AUTHOR]

c-KIT is an important diagnostic marker in salivary gland tumours and is expressed in most adenoid cystic carcinomas. Histologically similar salivary gland tumours with variable immunohistochemical expression for c-KIT pose a challenge and make diagnostic reliability ambivalent. An electronic search was performed in MEDLINE by PubMed, Google Scholar, Scopus, Trip, Cochrane Library, and EMBASE up to 31 December 2023, without period restriction. The articles that investigated CD117 or c-KIT in salivary gland tumours were included for review. Sensitivity, specificity, and positive and negative predictive values of c-KIT immunohistochemical expressions were derived and subjected to meta-analysis using Open Meta analyst for Sierra software. The risk of bias in selected studies was analysed using the QUADAS-2 tool, and RevMan 5.4 was used to output the result. Forty-three articles were reviewed, and 2285 salivary gland cases were analysed. Adenoid cystic carcinoma had an overall expression of 84.9%. A similar expression was found in epimyoepithelial carcinoma (79.1%), lymphoepithelial carcinoma (75%), myoepithelial carcinoma (60.8%), monomorphic adenoma (94.1%), and pleomorphic adenoma (74.7%). The sensitivity, specificity, and positive and negative predictive values of c-KIT/CD117 for adenoid cystic carcinoma with other salivary gland tumours were 84.99%, 69.09%, 84.79%, and 69.41%, respectively. Current evidence shows that c-KIT, despite its sensitivity, is not specific and therefore cannot be a useful diagnostic marker for distinguishing adenoid cystic carcinoma from other salivary gland tumours. Further research on other salivary gland tumours that exhibit comparable expression is necessary to validate the diagnostic accuracy of c-KIT. [ABSTRACT FROM AUTHOR]

Mast cell tumor (MCT) is a common skin cancer in dogs that has a wide range of clinical behaviors. The purpose of this study was to develop a novel multicolor flow cytometry (FC) panel that will enable the quantification of candidate prognostic markers (Ki-67 and pKIT) in fine needle aspirate (FNA) samples prior to surgical removal of the tumors. FNA of canine MCTs and the NI-1 cell line were utilized to develop a FC panel that includes a viability dye (FVS620, BD Biosciences; 7-AAD, Invitrogen) and the following primary conjugated antibodies: CD117-PE (ACK45, BD Biosciences), pKIT-A647 (polyclonal bs-3242R, BIOSS) and Ki-67- FITC (20Raj1, eBioscience; MIB-1, DAKO). A total of nine FNA samples of canine MCTs were collected, seven out which produced sufficient cells for FC analysis. The Ki-67 antibody clone 20Raj1 produced a positive signal when applied to blood leukocytes but failed to provide robust labeling of neoplastic mast cells. The Ki-67 antibody clone MIB-1 delivered a superior staining quality in both the NI-1 cells and primary MCT cells. CD117-PE signal was adequate post fixation and permeabilization and in the combination of 7-AAD. pKIT produced non-specific staining and was not suitable for this multicolor FC panel. In conclusion, FNA samples of canine MCTs can often yield adequate cell numbers for FC analysis, and a multicolor FC panel was developed that can detect Ki-67 in canine mast cells. This would permit further studies into the potential use of this panel for canine cutaneous and subcutaneous MCT prognostication purposes. [ABSTRACT FROM AUTHOR]

Primary adenoid cystic carcinoma (ACC) accounts for less than 0.2 % of all primary lung malignancies. Here we present two cases of lung ACC (ACCL), first is a 65-year-old female who was diagnosed with ACCL and surgically treated at another institution. She presented with recurrent tumor which was resected at our hospital. No adjuvant treatment was given, and she is without any signs of residual tumor or recurrence after 6 months. The second case is a 68-year-old female with a right upper lobe nodule noticed in 2017 but declined biopsy due to fear of possible complications. In 2022 she underwent biopsy at our institution which showed ACCL and was treated surgically without adjuvant therapy. Till date she is with no evidence of residual tumor or recurrence. Multiple disciplines need to work together to provide the best patient care from accurate diagnosis to surgical resection and additional therapy. More research is needed to generate guidelines for treatment of this rare malignancy, especially the indications for chemotherapy.

Background and purpose: Prostate cancer is the second cause of cancer-related death in men. Early diagnosis and identification of prognostic factors help to predict clinical outcome and select the most effective treatment protocol in each patient. The relationship between CD117 expression and various tumor prognoses has been identified and there is evidence for the role of this marker in prostate cancer pathogenesis. So, the aim of this study was to evaluate CD117 marker expression in prostate benign hyperplasia and adenocarcinoma, and to find its association with Gleason grade. Materials and methods: In this cross-sectional study, paraffin blocks of tissue samples obtained from 85 patients with prostatic benign hyperplasia and 78 patients with prostatic adenocarcinoma, who referred to Shahid Mostafa Khomeini hospital during 2018 to 2021, were immunohistochemically stained by anti-CD117 antibody. Membranous and cytoplasmic staining in more than 10% of epithelial tumor cells was considered as positive result. Results: Positive CD117 expression was found in 27.1% of prostatic benign hyperplasia and 50% of prostatic adenocarcinoma samples showed a statistically significant difference (P=0.003). There was no significant relationship between CD117 status expression and primary Gleason grade in prostatic adenocarcinoma samples (P=0.166); however, secondary Gleason grade and total Gleason score had a significant relationship with CD117 expression status (P=0.002 and P=0.017, respectively). Conclusion: CD117 expression was higher in prostatic carcinoma compared to benign prostatic hyperplasia and its higher expression was associated with higher Gleason grade as one of the most important prognostic factors in prostatic carcinoma

We identified a young female patient admitted for suspected renal malignancy. Partial nephrectomy was performed after imaging evaluation and discussion. Postoperative biopsy pathology reported multiple low-grade eosinophilic renal tumors (LOTs) with angiomyolipoma growth. After reviewing the data, we found that LOT was mostly solitary and occurred in middle-aged and elderly patients. This case is unique and we share it to improve the understanding of this disease. [ABSTRACT FROM AUTHOR]

Background and purpose: Prostate cancer is the second cause of cancer-related death in men. Early diagnosis and identification of prognostic factors help to predict clinical outcome and select the most effective treatment protocol in each patient. The relationship between CD117 expression and various tumor prognoses has been identified and there is evidence for the role of this marker in prostate cancer pathogenesis. So, the aim of this study was to evaluate CD117 marker expression in prostate benign hyperplasia and adenocarcinoma, and to find its association with Gleason grade. Materials and methods: In this cross-sectional study, paraffin blocks of tissue samples obtained from 85 patients with prostatic benign hyperplasia and 78 patients with prostatic adenocarcinoma, who referred to Shahid Mostafa Khomeini hospital during 2018 to 2021, were immunohistochemically stained by anti-CD117 antibody. Membranous and cytoplasmic staining in more than 10% of epithelial tumor cells was considered as positive result. Results: Positive CD117 expression was found in 27.1% of prostatic benign hyperplasia and 50% of prostatic adenocarcinoma samples showed a statistically significant difference (P=0.003). There was no significant relationship between CD117 status expression and primary Gleason grade in prostatic adenocarcinoma samples (P=0.166); however, secondary Gleason grade and total Gleason score had a significant relationship with CD117 expression status (P=0.002 and P=0.017, respectively). Conclusion: CD117 expression was higher in prostatic carcinoma compared to benign prostatic hyperplasia and its higher expression was associated with higher Gleason grade as one of the most important prognostic factors in prostatic carcinoma. [ABSTRACT FROM AUTHOR]

One of the largest challenges to the implementation of cardiac cell therapy is identifying selective reparative targets to enhance stem/progenitor cell therapeutic efficacy. In this work, we hypothesized that such a target could be an urokinase-type plasminogen activator receptor (uPAR)—a glycosyl-phosphatidyl-inositol-anchored membrane protein, interacting with urokinase. uPAR is able to form complexes with various transmembrane proteins such as integrins, activating intracellular signaling pathway and thus regulating multiple cell functions. We focused on studying the CD117+ population of cardiac mesenchymal progenitor cells (MPCs), expressing uPAR on their surface. It was found that the number of CD117+ MPCs in the heart of the uPAR−/− mice is lower, as well as their ability to proliferate in vitro compared with cells from wild-type animals. Knockdown of uPAR in CD117+ MPCs of wild-type animals was accompanied by a decrease in survival rate and Akt signaling pathway activity and by an increase in the level of caspase activity in these cells. That suggests the role of uPAR in supporting cell survival. After intramyocardial transplantation of uPAR(−) MPCs, reduced cell retention and angiogenesis stimulation were observed in mice with myocardial infarction model compared to uPAR(+) cells transplantation. Taken together, the present results appear to prove a novel mechanism of uPAR action in maintaining the survival and angiogenic properties of CD117+ MPCs. These results emphasize the importance of the uPAR as a potential pharmacological target for the regulation of reparative properties of myocardial mesenchymal progenitor cells. [ABSTRACT FROM AUTHOR]

Background: Mast cells influence tumour growth, neo-angiogenesis and the propensity for metastasis by contributing to innate and adaptive immune responses in the tumour microenvironment. The number of mast cells has increased in various malignant tumours and their abundance has been associated with either a favourable or unfavourable prognosis. This study investigated the significant difference in stromal mast cell density among multiple prognostic factor groups in invasive breast carcinoma. Methods: CD117 (c-KIT) antibodies were used to stain 160 formalin-fixed and paraffinembedded invasive breast carcinoma tissues to demonstrate the presence of mast cells. Then the labelled mast cells were counted in 10 fields at 400x magnification and the mean value was used to represent the mast cell density. Results: The demographic distribution revealed that most patients were 40 years old or older (92.5%) and of Malay ethnicity (66.3%). With regard to prognostic factors, the most prevalent subtype was invasive carcinoma of no special type (80.6%), followed by tumour grade 3 (41.3%), T2 tumour size (63.1%), N0 lymph node stage (51.3%), presence of lymphovascular invasion (59.4%), positive oestrogen (64.4%) and progesterone receptors (53.1%), and negative human epidermal growth factor receptor 2 (HER2) expression (75.0%). However, there was no significant difference in stromal mast cell density among the different demographic and prognostic factor groups in invasive breast carcinoma. Conclusion: The findings from this study suggest that stromal mast cells do not play a significant role in preventing or promoting tumour growth in invasive breast carcinoma. [ABSTRACT FROM AUTHOR]

Introduction. Chromophobe renal cell carcinoma (chromophobe RCC) is the third major subcategory of renal tumors after clear cell RCC and papillary RCC, accounting for approximately 5% of all RCC subtypes. Other oncocytic neoplasms seen commonly in surgical pathology practice include the eosinophilic variant of chromophobe RCC, renal oncocytoma, and low-grade oncocytic unclassified RCC. Methods. In our recent next-generation sequencing based study, we nominated a lineage-specific novel biomarker LINC01187 (long intergenic non-protein coding RNA 1187) which was found to be enriched in chromophobe RCC. Like KIT (cluster of differentiation 117; CD117), a clinically utilized chromophobe RCC related biomarker, LINC01187 is expressed in intercalated cells of the nephron. In this follow-up study, we performed KIT immunohistochemistry and LINC01187 RNA in situ hybridization (RNA-ISH) on a cohort of chromophobe RCC and other renal neoplasms, characterized the expression patterns, and quantified the expression signals of the two biomarkers in both primary and metastatic settings. Results. LINC01187, in comparison to KIT, exhibits stronger and more uniform expression within tumors while maintaining temporal and spatial consistency. LINC01187 also is devoid of intra-tumoral heterogeneous expression pattern, a phenomenon commonly noted with KIT. Conclusions. LINC01187 expression can augment the currently utilized KIT assay and help facilitate easy microscopic analyses in routine surgical pathology practice. [ABSTRACT FROM AUTHOR]

Extraintestinal gastrointestinal stromal tumors (EGISTs) are rare stromal tumors involving mesentery, omentum, and retroperitoneum. EGISTs of the pelvic cavity are extremely uncommon, and till date, no case of pure epithelioid type arising from the pelvic cavity has been reported. They pose a diagnostic pitfall as they may mimic ovarian malignancy. We present a unique case of an epithelioid extraintestinal stromal tumor arising from the pelvic cavity. A 43-43-year-old woman presented with complaints of abdominal pain and menstrual irregularities. Ultrasound examination revealed a large well-defined hypoechoic mass in the right pelvic cavity with a possible site of origin from the right ovary. A total hysterectomy with bilateral salpingo-oophorectomy was done. Histopathological examination revealed an encapsulated tumor comprising predominantly of nests and lobules of epithelioid cells with round-to-oval nuclei, vesicular chromatin, and moderate amount of eosinophilic to clear cytoplasm. Mitotic activity was brisk along with focal areas of necrosis. On immunohistochemistry, tumor cells were diffusely and strongly positive for DOG1 and CD117. They were negative for smooth muscle actin, vimentin, S-100, and HMB-45. Based on these findings, a final diagnosis of the high-grade GIST epithelioid variant was made. It is crucial to make the correct preoperative diagnosis of GIST, since these patients may benefit from neoadjuvant imatinib, especially in case of large tumor size. [ABSTRACT FROM AUTHOR]

The article "Negative Expression of CD117 Predicted Inferior OS and PFS in Acute Promyelocytic Leukemia" published in the International Journal of Laboratory Hematology discusses a study on the prognostic significance of CD117 in acute promyelocytic leukemia (APL). The researchers found that CD117 was an independent adverse prognostic factor for overall survival (OS) and progression-free survival (PFS) in patients with APL. The study raises concerns about the statistical methods used and suggests improvements for future research in this area. [Extracted from the article]

Simple Summary: The only cure for children with Ewing sarcoma (ES) is surgery. Unfortunately, surgeons are often not able to differentiate healthy from malignant tissue. Fluorescent imaging during the operation will facilitate recognition of malignant cells, but unfortunately there are no ES specific tracers available yet. We searched for proteins on ES cells that could be used as a target against which specific tracers could be developed. The most promising proteins, CD99, CD117, and GD2, were found in paraffin-embedded tissue samples collected from ES patients. Tracers against CD99 and CD117, consisting of monoclonal antibodies attached with a fluorescent dye, showed positive signals on cultured ES cells. In a proof-of-concept study, these tracers were topically applied on fresh ES tissue, showing a signal in the tumor. Our results indicate the applicability for fluorescence-guided surgery of ES-based tracers, but these data have to be confirmed in a larger cohort of pediatric ES patients. Fluorescence-guided surgery (FGS), based on fluorescent tracers binding to tumor-specific biomarkers, could assist surgeons to achieve complete tumor resections. This study evaluated potential biomarkers for FGS in pediatric Ewing sarcoma (ES). Immunohistochemistry (IHC) was performed to assess CD99, CXCR4, CD117, NPY-R-Y1, and IGF-1R expression in ES biopsies and resection specimens. LINGO-1 and GD2 evaluation did not work on the acquired tissue. Based on the immunoreactive scores, anti-CD99 and anti-CD117 were evaluated for binding specificity using flow cytometry and immunofluorescence microscopy. Anti-GD2, a tracer in the developmental phase, was also tested. These three tracers were topically applied to a freshly resected ES tumor and adjacent healthy tissue. IHC demonstrated moderate/strong CD99 and CD117 expression in ES tumor samples, while adjacent healthy tissue had limited expression. Flow cytometry and immunofluorescence microscopy confirmed high CD99 expression, along with low/moderate CD117 and low GD2 expression, in ES cell lines. Topical anti-CD99 and anti-GD2 application on ES tumor showed fluorescence, while anti-CD117 did not show fluorescence for this patient. In conclusion, CD99-targeting tracers hold promise for FGS of ES. CD117 and GD2 tracers could be potential alternatives. The next step towards development of ES-specific FGS tracers could be ex vivo topical application experiments on a large cohort of ES patients. [ABSTRACT FROM AUTHOR]

Introduction: Ovarian cancer is one of leading causes of cancer related death in gynecology. CD117 is a tyrosine kinase receptor that plays an important role in regulation of apoptosis, cell proliferation and adhesion by binding to its ligand-stem cell factor. Recent studies demonstrated its aberrant overexpression in various malignancies and concluded that it may play a pivotal role in carcinogenesis. Aim: To evaluate CD117 expression in ovarian surface epithelial tumours. Materials and Methods: This retrospective study included 30 ovarian epithelial borderline, low and highly malignant tumours' formalin-fixed paraffin-blocks (FFPE) tissue blocks. Tissue sections were subjected to the routine haematoxylin-eosin stain and with the anti-CD117 immunohistochemically. Results: There is a high significant difference in CD117 expression between borderline and malignant groups (P = 0.001). Additionally, there was significant difference in expression in relation to histopathological type (serous versus non-serous) in low-grade and the high-grade ovarian surface epithelial tumours (p=0.04, p=0.035 respectively). Tumour grade and stage strongly correlates with CD117 expression (p=0.014, p=0.019 respectively). Conclusion: We concluded that CD117 expression was significantly correlated with higher ovarian tumour grade and stage. [ABSTRACT FROM AUTHOR]

Papillary glioneuronal tumors are rare neoplasm, accounting only <0.02% of all intracranial tumors. They are generally low grade usually occur in the temporal lobe near the third ventricle. We report an extremely rare case of intraventricular tumor with a high proliferation index. CD 117 expression found in our case is the first study to the best of our knowledge to be described in these tumors. The clinical and diagnostic significance of this finding is subject to further studies. [ABSTRACT FROM AUTHOR]

Extraintestinal gastrointestinal stromal tumors (EGISTs) are rare stromal tumors involving mesentery, omentum, and retroperitoneum. EGISTs of the pelvic cavity are extremely uncommon, and till date, no case of pure epithelioid type arising from the pelvic cavity has been reported. They pose a diagnostic pitfall as they may mimic ovarian malignancy. We present a unique case of an epithelioid extraintestinal stromal tumor arising from the pelvic cavity. A 43-43-year-old woman presented with complaints of abdominal pain and menstrual irregularities. Ultrasound examination revealed a large well-defined hypoechoic mass in the right pelvic cavity with a possible site of origin from the right ovary. A total hysterectomy with bilateral salpingo-oophorectomy was done. Histopathological examination revealed an encapsulated tumor comprising predominantly of nests and lobules of epithelioid cells with round-to-oval nuclei, vesicular chromatin, and moderate amount of eosinophilic to clear cytoplasm. Mitotic activity was brisk along with focal areas of necrosis. On immunohistochemistry, tumor cells were diffusely and strongly positive for DOG1 and CD117. They were negative for smooth muscle actin, vimentin, S-100, and HMB-45. Based on these findings, a final diagnosis of the high-grade GIST epithelioid variant was made. It is crucial to make the correct preoperative diagnosis of GIST, since these patients may benefit from neoadjuvant imatinib, especially in case of large tumor size.

Mitochondrial neurogastrointestinal encephalomyopathy is an extremely rare (1–9:1 000 000, Orphanet, 2021) multisystem genetic disease caused by mutations in the TYMP gene encoding the enzyme thymidine phosphorylase.The article presents the data of a thirteen‑year survey on 40‑year‑old patient D. with clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy syndrome associated with the previously undescribed missense mutation c.1301G>T (p.Gly434Val) of the TYMP gene. Detailed clinical picture (gastrointestinal dysfunction, cachexia, blepharoptosis, ophthalmoparesis, peripheral polyneuropathy and leukoaraiosis), electroneuromyography data (demyelination with secondary axonopathy), high blood serum level of dihydrothymine together with normal levels of thymidine and deoxyuridine made it possible to verify the diagnosis. Histopathological examination revealed atrophy of the longitudinal (outer) muscle layer of the small and large intestines and a significant decrease in the number of CD117+ cells (telocytes), signs of damage to the striated skeletal muscles of a mixed nature with a predominance of the myogenic pattern, as well the destruction of the myelin sheaths of peripheral nerves. Histochemical examination did not reveal “ragged red fibers” characteristic of mitochondrial pathology. Transmission electron microscopy demonstrated the presence of megalomitochondria in the myocardium.

Abstract Background Gastrointestinal stromal tumor (GIST) is a malignant mesenchymal neoplasm described in humans, dogs, and cats. A hallmark of diagnosis for GISTs is positive immunohistochemical labelling with c-Kit (CD117). The differentiation of GIST from other mesenchymal neoplasms of the gastrointestinal tract is pivotal to allow for initiation of appropriate treatment. In humans, cystic GIST has been described, though this has not been reported in dogs. In humans, the cystic form of GIST has been associated with a favorable prognosis. In the present paper, we report a case of multilocular cystic GIST in a dog, which has not previously been described in this species. Case presentation A ten-year-old, male-entire Maltese terrier mix breed dog presented with a large cystic mural mass of the duoedenum and orad jejunum. Histopathology and positive immunohistochemical staining with CD117 confirmed a diagnosis of GIST. No evidence of metastasis was detected on routine staging with abdominal sonography and thoracic radiography at the time of diagnosis. Surgical resection was performed and toceranib therapy was initiated post-operatively. Metastasis was documented 251 days after surgery on computed tomography. Due to clinical deterioration, the patient was humanely euthanised 370 days after surgical excision. Conclusions There are few differential diagnoses for large multilocular cystic intra-abdominal masses in dogs. This case presents a previously undescribed presentation of gastrointestinal stromal tumor in the dog as a predominantly multilocular cystic mass. It remains unclear if the cystic form of GIST may represent a favorable prognosis in dogs.

Simple Summary: In veterinary medicine, methods such as histological grading, immunohistochemistry and mutation analysis of the c-kit gene are tools to assess the prognosis and treatment of canine cutaneous mast cell tumours. These methods have not yet been applied and evaluated on a large scale for mast cell tumours of the dog's toe, as these digital mast cell tumours are considered a subset of the cutaneous forms. Mast cell tumours can be more aggressive at certain sites. Therefore, the aim of this study was to apply these methods to 68 dogs with digital mast cell tumours. Even though only a few digital mast cell tumours were histologically poorly differentiated, more than half had immunohistochemical findings that could indicate an unfavourable prognosis. Mutations in the c-kit gene were found as well. Moreover, French Bulldogs—a breed that tends to develop benign variants at other sites on the skin—were more likely to have poorly differentiated tumours. Although outcome data were not available, the results of this study may contribute to a better understanding of canine mast cell tumours of the toe. Grading, immunohistochemistry and c-kit mutation status are criteria for assessing the prognosis and therapeutic options of canine cutaneous mast cell tumours (MCTs). As a subset, canine digital MCTs have rarely been explored in this context. Therefore, in this retrospective study, 68 paraffin-embedded canine digital MCTs were analysed, and histological grading was assessed according to Patnaik and Kiupel. The immunohistochemical markers KIT and Ki67 were used, as well as polymerase chain reaction (PCR) for mutational screening in c-kit exons 8, 9, 11 and 14. Patnaik grading resulted in 22.1% grade I, 67.6% grade II and 10.3% grade III tumours. Some 86.8% of the digital MCTs were Kiupel low-grade. Aberrant KIT staining patterns II and III were found in 58.8%, and a count of more than 23 Ki67-positive cells in 52.3% of the cases. Both parameters were significantly associated with an internal tandem duplication (ITD) in c-kit exon 11 (12.7%). French Bulldogs, which tend to form well-differentiated cutaneous MCTs, had a higher proportion of digital high-grade MCTs and ITD in c-kit exon 11 compared with mongrels. Due to its retrospective nature, this study did not allow for an analysis of survival data. Nevertheless, it may contribute to the targeted characterisation of digital MCTs. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are tissue-resident innate immune cells that express the high-affinity receptor for immunoglobulin E and are responsible for host defense and an array of diseases related to immune system. We aimed in this study to characterize the pathways and gene signatures of human cord blood-derived MCs (hCBMCs) in comparison to cells originating from CD34− progenitors using next-generation knowledge discovery methods. CD34+ cells were isolated from human umbilical cord blood using magnetic activated cell sorting and differentiated into MCs with rhIL-6 and rhSCF supplementation for 6–8 weeks. The purity of hCBMCs was analyzed by flow cytometry exhibiting the surface markers CD117+CD34−CD45−CD23−FcεR1αdim. Total RNA from hCBMCs and CD34− cells were isolated and hybridized using microarray. Differentially expressed genes were analyzed using iPathway Guide and Pre-Ranked Gene Set Enrichment Analysis. Next-generation knowledge discovery platforms revealed MC-specific gene signatures and molecular pathways enriched in hCBMCs and pertain the immunological response repertoire.

Objectives Hypocellular bone marrow (BM) disorders comprise heterogeneous entities associated with peripheral cytopenias and decreased production of hematopoietic cells in BM. This study was undertaken to analyze immunohistochemical expression of CD34, CD117, and p53 in morphologically diagnosed patients of hypocellular BM (aplastic anemia [AA], hypocellular myelodysplastic syndrome [h-MDS], and hypocellular acute myeloid leukemia [h-AML]). Materials and Methods BM specimens were obtained from patients presenting with pancytopenia/bicytopenia. On 30 patients diagnosed as hypocellular BM, immunohistochemistry (IHC) for CD34, CD117, and p53 was performed. Results BM cellularity was

IntroductionMultiple myeloma (MM) is a plasma cell neoplasm that constitutes 10–15% of all hematopoietic neoplasms. Kenya is placed among the top five African countries for MM incidence and MM-related mortality. Prior studies have suggested that the aberrant expression of Cyclin D1, CD56, CD117 and Ki-67 on neoplastic plasma cells is useful in disease prognostication. The prevalence and significance of expression of these markers in a cohort of MM cases in Kenya has not been studied previously.MethodsA retrospective cross-sectional study was carried out at the Aga Khan University Hospital, Nairobi. The study population included 83 MM cases with available trephine blocks archived between 1st of January 2009 and 31st of March 2020. Immunohistochemical expression of Cyclin D1, CD56, CD117, and Ki-67 was analyzed and scored. The biomarkers were described using frequencies based on the positive and negative results. Fisher’s exact test was used to determine the association between the immunophenotypic markers and categorical variables.ResultsOf the 83 selected cases, expression of Cyclin D1, CD56, CD117 and Ki-67 was identified in 28.9, 34.9, 7.2, and 50.6%, respectively. Cyclin D1 positivity was significantly associated with hypercalcemia. Absence of CD117 expression was noted to be associated with adverse risk parameters including an IgA isotype or light chain disease, International Staging System (ISS) stage III disease, abnormal baseline serum free light chains (sFLC) and a high plasma cell burden.ConclusionCyclin D1 expression was congruent with previously reported studies. The frequency of CD56 and CD117 expression was lower than previously reported. This may be due to differences in disease biology between the study populations. Approximately half of cases were Ki-67 positive. Our data showed limited associations between the expression of studied markers and clinicopathologic variables. However, this could be attributed to the small study sample size. We would recommend further characterization of the disease in a larger prospective study with the inclusion of survival outcomes and cytogenetic studies.

The study aimed to evaluate the effects and relationships between mast cells in the matrix, mast cell enzymes tryptase and chymase, epithelial proliferation, microvascular density, and bone destruction in cholesteatoma. Thirty-five biopsies diagnosed with cholesteatoma and seven healthy skin tissues taken from the retro-auricular region for control were evaluated. Immunohistochemical studies were performed with CD117, CD34, Ki-67, chymase, and tryptase antibodies, in a single session for all cases and the control group. The relationship between erosion size and antibody load was determined. The mean cholesteatoma epithelium Ki-67 was higher than the control group (p < 0.001). CD117-positive mast cells, chymase-positive mast cells, tryptase-positive mast cells, and microvessel density were significantly higher in the cholesteatoma matrix compared to the control group (p < 0.002, p < 0.001, p < 0.005). In the group with bone erosion scores of two and above, immunohistochemical markers tended to be higher. A positive correlation was found between CD117 and chymase, tryptase, and microvessel density; between tryptase, chymase, and microvessel density; and between chymase and microvessel density. CD117-positive mast cells and chymase-positive mast cells stimulate angiogenesis, increase the epithelium's proliferative capacity in the cholesteatoma matrix, and form cholesteatoma. The increased proliferation of cholesteatoma epithelium and increased vascular density in the matrix exacerbate bone erosion. [ABSTRACT FROM AUTHOR]

Molecular-based subclassifications of breast cancer are important for identifying treatment options and stratifying the prognosis in breast cancer. This study aimed to assess the prognosis relative to disease-free survival (DFS) and overall survival (OS) in patients with triple-negative breast cancer (TNBC) and other subtypes, using a biomarker panel including cytokeratin 5 (CK5), cluster of differentiation 117 (CD117), and epidermal growth factor receptor (EGFR). This cohort–case study included histologically confirmed breast carcinomas as cohort arm. From a total of 894 patients, 572 patients with early breast cancer, sufficient clinical data, and archived tumor tissue were included. Using the immunohistochemical markers CK5, CD117, and EGFR, two subgroups were formed: one with all three biomarkers negative (TBN) and one with at least one of those three biomarkers positive (non-TBN). There were significant differences between the two biomarker subgroups (TBN versus non-TBN) in TNBC for DFS (p = 0.04) and OS (p = 0.02), with higher survival rates (DFS and OS) in the non-TBN subgroup. In this study, we found the non-TBN subgroup of TNBC lesions with at least one positive biomarker of CK5, CD117, and/or EGFR, to be associated with longer DFS and OS. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors are the most common mesenchymal tumors of gastrointestinal tract which comprise

Background: Gastrointestinal stromal tumor (GIST) is a malignant mesenchymal neoplasm described in humans, dogs, and cats. A hallmark of diagnosis for GISTs is positive immunohistochemical labelling with c-Kit (CD117). The differentiation of GIST from other mesenchymal neoplasms of the gastrointestinal tract is pivotal to allow for initiation of appropriate treatment. In humans, cystic GIST has been described, though this has not been reported in dogs. In humans, the cystic form of GIST has been associated with a favorable prognosis. In the present paper, we report a case of multilocular cystic GIST in a dog, which has not previously been described in this species. Case presentation: A ten-year-old, male-entire Maltese terrier mix breed dog presented with a large cystic mural mass of the duoedenum and orad jejunum. Histopathology and positive immunohistochemical staining with CD117 confirmed a diagnosis of GIST. No evidence of metastasis was detected on routine staging with abdominal sonography and thoracic radiography at the time of diagnosis. Surgical resection was performed and toceranib therapy was initiated post-operatively. Metastasis was documented 251 days after surgery on computed tomography. Due to clinical deterioration, the patient was humanely euthanised 370 days after surgical excision. Conclusions: There are few differential diagnoses for large multilocular cystic intra-abdominal masses in dogs. This case presents a previously undescribed presentation of gastrointestinal stromal tumor in the dog as a predominantly multilocular cystic mass. It remains unclear if the cystic form of GIST may represent a favorable prognosis in dogs. [ABSTRACT FROM AUTHOR]

The prognostic value of CD56 and CD117 expression on myeloma cells is controversial. This study aims to analyze the correlation of CD56 and CD117 expression with cytogenetic abnormalities and survival. A total of 128 patients with newly diagnosed multiple myeloma (NDMM) were recruited in this single-center retrospective study. Flow cytometry and FISH tests of marrow cells were performed for all of the subjects. The statistical methods included a chi-squared test, univariate and multivariate COX regressions, and a Kaplan-Meier survival curve analysis. Regarding the cytogenetics, the incidence of IgH/FGFR3 translocation was more frequent in patients with a negative CD56 (p = 0.003). CD56 negativity was an independent adverse factor associated with a poor prognosis (p = 0.019) and indicated a shorter overall survival (OS) (p = 0.021). Patients with dual negative CD56 and CD117 trended toward a poorer OS (CD56−CD117− vs. CD56+CD117−, p = 0.011; CD56−CD117− vs. CD56+CD117+, p = 0.013). In conclusion, CD56 is a prognostic marker that independently affects OS and is associated with adverse cytogenetic abnormalities. Patients with a dual negativity of CD56 and CD117 have a worse clinical outcome. [ABSTRACT FROM AUTHOR]

Telocytes (TCs) are a vital constituent of interstitial tissue. They contribute to regulating cell function in heterotypic connections via direct contact or paracrine singling. Few studies mentioned intraepithelial TCs; however, they have been identified with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In this study, we investigated the intraepithelial and interstitial TCs using immunohistochemistry (IHC) and TEM. TCs can be identified by their distinctive telopodes (TPs), which consist of podoms and podomere, using TEM and immunohistochemical staining with CD34, CD117, and VEGF antibodies. Intraepithelial TCs established heterocontact with the lamellar capillary and interstitial TCs connected with the blood vessel in lamina propria. Intraepithelial TCs established direct contact with epithelial cells, which formed the lymph space while interstitial TCs connected with the secondary vascular vessels. The study provides evidence for TCs' heterocontact with lamellar blood capillaries, the blood vessels, chloride cells, and immune cells, such as rodlet cells and lymphocytes. In conclusion, TCs have a role in regulating respiratory activities, maintaining osmotic pressure, modulating the immune response, and conducting immunosurveillance. Research highlights: We investigated the intraepithelial and interstitial TCs using immunohistochemistry (IHC) and TEM.TCs can be identified by their distinctive telopodes (TPs), which consist of podoms and podomere, using TEM and immunohistochemical staining with CD34, CD117, and VEGF antibodies.Intraepithelial TCs established heterocontact with the lamellar capillary and interstitial TCs connected with the blood vessel in lamina propria. [ABSTRACT FROM AUTHOR]