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Anatomical Record (Hoboken, N.J. : 2007) Aug 2024Expression of alpha-synuclein (Syn), a presynaptic neuronal protein, was immunohistochemically examined in intact rat submandibular, sublingual, and lingual glands. The...
Expression of alpha-synuclein (Syn), a presynaptic neuronal protein, was immunohistochemically examined in intact rat submandibular, sublingual, and lingual glands. The submandibular gland contained abundant periductal Syn-immunoreactive (-ir) nerve fibers. Abundant Syn-ir varicosities were present in acini of the sublingual and serous lingual glands. By confocal laser scanning microscopy, Syn-ir nerve fibers around smooth muscle actin (SMA)-ir cells alone were infrequent; however, those around aquaporin-5 (AQP5)-ir cells alone and both SMA- and AQP5-ir cells were abundant in the sublingual and serous lingual glands. SMA-ir cells were occasionally immunoreactive for toll-like receptor 4, a Syn receptor. Syn-ir nerve fibers contained tyrosine hydroxylase (TH) in the submandibular gland and choline acetyltransferase (ChAT) in all examined salivary glands. In the superior cervical (SCG), submandibular, and intralingual ganglia, sympathetic and parasympathetic neurons co-expressed Syn with TH and ChAT, respectively. SCG neurons innervating the submandibular gland contained mostly Syn. In the thoracic spinal cord, 14.7% of ChAT-ir preganglionic sympathetic neurons co-expressed Syn. In the superior salivatory nucleus, preganglionic parasympathetic neurons projecting to the lingual nerve co-expressed Syn and ChAT. The present findings indicate that released Syn acts on myoepithelial cells. Syn in pre- and post-ganglionic neurons may regulate neurotransmitter release and salivary volume and composition.
Topics: Animals; Rats; Salivary Glands; Male; alpha-Synuclein; Choline O-Acetyltransferase; Aquaporin 5; Tyrosine 3-Monooxygenase; Submandibular Gland; Rats, Wistar; Rats, Sprague-Dawley; Immunohistochemistry
PubMed: 38284507
DOI: 10.1002/ar.25395 -
Experimental and Molecular Pathology Feb 2024Neoadjuvant chemotherapy (NCT) can induce a pathological complete response (pCR) in breast cancer patients, leading to improved outcomes. However, predicting which...
CD10 expression as a potential predictor of pathological complete response in ER-negative and triple-negative breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy.
BACKGROUND
Neoadjuvant chemotherapy (NCT) can induce a pathological complete response (pCR) in breast cancer patients, leading to improved outcomes. However, predicting which patients will achieve pCR remains a challenge. CD10, a myoepithelial marker, has shown diagnostic and prognostic value in metastatic tumors. Its potential as a predictor of chemosensitivity to anthracycline-based NCT in breast cancer is unknown.
AIM
This retrospective study aimed to investigate the potential of CD10 cancer cell expression as a predictive marker of chemosensitivity in breast cancers treated with anthracycline-based neoadjuvant chemotherapy.
METHODS
We analyzed 130 patients with invasive ductal carcinoma who received anthracycline-based NCT. CD10 expression was assessed by immunohistochemistry on pre-treatment biopsies. Statistical analysis evaluated the association between CD10 expression and pCR rates.
RESULTS
Univariate analysis revealed that ER-positive and CD10-negative tumors had lower pCR rates [OR 7.4830 (95% CI 2.7762-20.1699); p = 0.0001]. Multivariate analysis confirmed ER status as a strong predictor of poor response [OR 0.085 (95% CI 0.024-0.30); p < 0.001] and CD10 expression as a predictor of a favourable response [OR 0.11 (0.8-0.19); p = 0.049]. CD10 expression significantly predicted pCR in ER-negative cases [OR 0.1098 (0.0268-0.4503); p = 0.0022] and triple-negative breast cancer [OR 0.0966 (95% CI 0.0270-0.3462); p = 0.0003]. Concordance was observed between core biopsies and excised samples.
CONCLUSION
Positive CD10 cancer cell expression may predict increased response to anthracycline-based neoadjuvant chemotherapy in ER-negative and triple-negative breast cancer cases. Further research is needed to validate these findings in larger cohorts and determine the clinical utility of CD10 as a predictive marker.
Topics: Humans; Female; Breast Neoplasms; Triple Negative Breast Neoplasms; Anthracyclines; Retrospective Studies; Receptor, ErbB-2; Neoadjuvant Therapy; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Biomarkers, Tumor
PubMed: 38281565
DOI: 10.1016/j.yexmp.2024.104885 -
Pathology, Research and Practice Feb 2024Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. ACC is composed of myoepithelial and epithelial neoplastic cells which grow...
Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. ACC is composed of myoepithelial and epithelial neoplastic cells which grow slowly and have a tendency for neural invasion. The long term prognosis is still relatively poor. Although several gene abnormalities, such as fusions involving MYB or MYBL1 oncogenes and the transcription factor gene NFIB, and overexpression of KIT have been reported in ACC, their precise functions in the pathogenesis of ACC remain unclear. We recently demonstrated that the elevated expression of Semaphorin 3A (SEMA3A), specifically expressed in myoepithelial neoplastic cells, might function as a novel oncogene-related molecule to enhance cell proliferation through activated AKT signaling in 9/10 (90%) ACC cases. In the current study, the patient with ACC whose tumor was negative for SEMA3A in the previous study, revisited our hospital with late metastasis of ACC to the cervical lymph node eight years after surgical resection of the primary tumor. We characterized this recurrent ACC, and compared it with the primary ACC using immunohistochemical methods. In the recurrent ACC, the duct lining epithelial cells, not myoepithelial neoplastic cells, showed an elevated Ki-67 index and increased cell membrane expression of C-kit, along with the expression of phosphorylated ERK. Late metastasis ACC specimens were not positive for β-catenin and lymphocyte enhancer binding factor 1 (LEF1), which were detected in the nuclei of perineural infiltrating cells in primary ACC cells. In addition, experiments with the GSK-3 inhibitor revealed that β-catenin pathway suppressed not only KIT expression but also proliferation of ACC cells. Moreover, stem cell factor (SCF; also known as KIT ligand, KITL) induced ERK activation in ACC cells. These results suggest that inactivation of Wnt/β-catenin signaling may promote C-kit-ERK signaling and cell proliferation of in metastatic ACC.
Topics: Humans; Carcinoma, Adenoid Cystic; beta Catenin; Catenins; Glycogen Synthase Kinase 3; Semaphorin-3A; Neoplasm Recurrence, Local; Salivary Gland Neoplasms; Wnt Signaling Pathway; Proto-Oncogene Proteins c-kit
PubMed: 38277753
DOI: 10.1016/j.prp.2024.155148 -
Cancers Jan 2024Breast cancer is predominantly an age-related disease, with aging serving as the most significant risk factor, compounded by germline mutations in high-risk genes like... (Review)
Review
Breast cancer is predominantly an age-related disease, with aging serving as the most significant risk factor, compounded by germline mutations in high-risk genes like /. Aging induces architectural changes in breast tissue, particularly affecting luminal epithelial cells by diminishing lineage-specific molecular profiles and adopting myoepithelial-like characteristics. ELF5 is an important transcription factor for both normal breast and breast cancer development. This review focuses on the role of ELF5 in normal breast development, its altered expression throughout aging, and its implications in cancer. It discusses the lineage-specific expression of ELF5, its regulatory mechanisms, and its potential as a biomarker for breast-specific biological age and cancer risk.
PubMed: 38275872
DOI: 10.3390/cancers16020431 -
International Journal of Cancer May 2024Ductal carcinoma in situ with microinvasion (DCISM) is a challenging subtype of breast cancer with controversial invasiveness and prognosis. Accurate diagnosis of DCISM...
Improving the diagnosis of ductal carcinoma in situ with microinvasion without immunohistochemistry: An innovative method with H&E-stained and multiphoton microscopy images.
Ductal carcinoma in situ with microinvasion (DCISM) is a challenging subtype of breast cancer with controversial invasiveness and prognosis. Accurate diagnosis of DCISM from ductal carcinoma in situ (DCIS) is crucial for optimal treatment and improved clinical outcomes. However, there are often some suspicious small cancer nests in DCIS, and it is difficult to diagnose the presence of intact myoepithelium by conventional hematoxylin and eosin (H&E) stained images. Although a variety of biomarkers are available for immunohistochemical (IHC) staining of myoepithelial cells, no single biomarker is consistently sensitive to all tumor lesions. Here, we introduced a new diagnostic method that provides rapid and accurate diagnosis of DCISM using multiphoton microscopy (MPM). Suspicious foci in H&E-stained images were labeled as regions of interest (ROIs), and the nuclei within these ROIs were segmented using a deep learning model. MPM was used to capture images of the ROIs in H&E-stained sections. The intensity of two-photon excitation fluorescence (TPEF) in the myoepithelium was significantly different from that in tumor parenchyma and tumor stroma. Through the use of MPM, the myoepithelium and basement membrane can be easily observed via TPEF and second-harmonic generation (SHG), respectively. By fusing the nuclei in H&E-stained images with MPM images, DCISM can be differentiated from suspicious small cancer clusters in DCIS. The proposed method demonstrated good consistency with the cytokeratin 5/6 (CK5/6) myoepithelial staining method (kappa coefficient = 0.818).
Topics: Humans; Female; Carcinoma, Intraductal, Noninfiltrating; Immunohistochemistry; Microscopy; Breast Neoplasms; Staining and Labeling; Neoplasm Invasiveness; Carcinoma, Ductal, Breast
PubMed: 38268429
DOI: 10.1002/ijc.34855 -
Modern Pathology : An Official Journal... Mar 2024Cutaneous mixed tumors exhibit a wide morphologic diversity and are currently classified into apocrine and eccrine types based on their morphologic differentiation. Some...
Cutaneous mixed tumors exhibit a wide morphologic diversity and are currently classified into apocrine and eccrine types based on their morphologic differentiation. Some cases of apocrine-type cutaneous mixed tumors (ACMT), namely, hyaline cell-rich apocrine cutaneous mixed tumors (HCR-ACMT) show a prominent or exclusive plasmacytoid myoepithelial component. Although recurrent fusions of PLAG1 have been observed in ACMT, the oncogenic driver of eccrine-type cutaneous mixed tumors (ECMT) is still unknown. The aim of the study was to provide a comprehensive morphologic, immunohistochemical, and molecular characterization of these tumors. Forty-one cases were included in this study: 28 cases of ACMT/HCR-ACMT and 13 cases of ECMT. After morphologic and immunohistochemical characterization, all specimens were analyzed by RNA sequencing. By immunohistochemistry, all cases showed expression of SOX10, but only ACMT/HCR-ACMT showed expression of PLAG1 and HMGA2. RNA sequencing confirmed the presence of recurrent fusion of PLAG1 or HMGA2 in all cases of ACMT/HCR-ACMT, with a perfect correlation with PLAG1/HMGA2 immunohistochemical status, and revealed internal tandem duplications of SOX10 (SOX10-ITD) in all cases of ECMT. Although TRPS1::PLAG1 was the most frequent fusion, HMGA2::WIF1 and HMGA2::NFIB were detected in ACMT cases. Clustering analysis based on gene expression profiling of 110 tumors, including numerous histotypes, showed that ECMT formed a distinct group compared with all other tumors. ACMT, HCR-ACMT, and salivary gland pleomorphic adenoma clustered together, whereas myoepithelioma with fusions of EWSR1, FUS, PBX1, PBX3, POU5F1, and KLF17 formed another cluster. Follow-up showed no evidence of disease in 23 cases across all 3 tumor types. In conclusion, our study demonstrated for the first time SOX10-ITD in ECMT and HMGA2 fusions in ACMT and further refined the prevalence of PLAG1 fusions in ACMT. Clustering analyses revealed the transcriptomic distance between these different tumors, especially in the heterogenous group of myoepitheliomas.
Topics: Humans; Adenoma, Pleomorphic; DNA-Binding Proteins; Myoepithelioma; Repressor Proteins; Salivary Gland Neoplasms; Skin Neoplasms; SOXE Transcription Factors; Sweat Gland Neoplasms; Transcription Factors
PubMed: 38266920
DOI: 10.1016/j.modpat.2024.100430 -
BMJ Case Reports Jan 2024A woman presented with a painless swelling in front of her right auricle, which, on examination, seemed to be a hard, immobile mass arising from the right parotid gland....
A woman presented with a painless swelling in front of her right auricle, which, on examination, seemed to be a hard, immobile mass arising from the right parotid gland. CT scan showed a heterogeneously enhancing mass lesion in the superficial lobe of the parotid gland with partial extension into the deep lobe. Fine needle aspiration cytology suggested a high-grade transformation (HGT) with the presence of bizarre tumour cells. She underwent a right-sided total parotidectomy with transient facial neuropraxia in the postoperative period. The final pathological diagnosis of the specimen came out to be epithelial myoepithelial carcinoma with HGT, which is a relatively rare entity, with no defined guidelines for management. Our patient was managed by surgical resection alone without any postoperative radiation therapy, and short-term follow-up results seem to suggest no recurrence.
Topics: Female; Humans; Parotid Gland; Carcinoma; Atrial Appendage; Biopsy, Fine-Needle; Contusions
PubMed: 38262715
DOI: 10.1136/bcr-2023-259364 -
Cureus Dec 2023A nipple adenoma is an epithelial tumor of the lactiferous ducts, typically affecting women aged 50-60 years old. This case report discusses a 52-year-old woman who...
A nipple adenoma is an epithelial tumor of the lactiferous ducts, typically affecting women aged 50-60 years old. This case report discusses a 52-year-old woman who developed a papillary adenoma of the right nipple after initiating oral estrogen replacement therapy (ERT) for perimenopausal symptoms. A 4 mm punch biopsy and subsequent immunohistochemistry stain revealed the proliferation of ductal structures consistent with a papillary adenoma and tumor cells expressing estrogen receptors (ER) and progesterone receptors (PR). Despite their benign nature, nipple adenomas may exhibit alterations in immunophenotype, including ER and PR expression, which could lead to potential tumor growth in women undergoing these treatments. This case describes the first reported growth of a nipple adenoma in the context of estrogen replacement therapy, highlighting a potential risk of hormone therapy in promoting hyperproliferation of benign tumors such as nipple adenomas. When utilizing ERT, it is important to weigh the potential advantages and risks, as its application in the management of vasomotor symptoms during menopause may increase the risk of both breast cancer and benign proliferative breast diseases. These considerations underscore the need for individualized therapy when approaching perimenopausal and postmenopausal care.
PubMed: 38249210
DOI: 10.7759/cureus.50843 -
NPJ Precision Oncology Jan 2024Gene expression analysis enhances proper cancer subtyping, a better understanding of the molecular characteristics of cancer, and strategies for precision medicine....
Gene expression analysis enhances proper cancer subtyping, a better understanding of the molecular characteristics of cancer, and strategies for precision medicine. However, salivary gland cancer (SGC) subtyping remains largely unexplored because of its rarity and diverse histopathological and immunological characteristics. This study aimed to determine whether the histological origin and immunological characteristics of SGC subtypes are intrinsic tumor immunity factors. We performed immune profiling of 94 RNA-seq of SGC tissues and found that the SGCs that originated from the excretory duct (ED), such as the salivary duct and mucoepidermoid carcinomas, exhibit higher immunity than those from the intercalated duct (ID), such as the adenoid cystic and myoepithelial carcinomas, based on the computationally predicted immune score (p < 0.001), immune cell enrichment in the tumor immune microenvironment (TIME) (p < 0.001), T-cell receptor diversity (p < 0.001), and expression of signal I (major histocompatibility complex, MHC, p < 0.001) and signal II (co-stimulatory, p < 0.001 and co-inhibitory, p < 0.001) genes. Further analysis revealed that tolerogenic dendritic cell-induced dysfunctional T-cell populations and T-cell exclusion in the TIME are the major immune evasive mechanisms of the ED-and ID-derived SGCs, respectively.
PubMed: 38245623
DOI: 10.1038/s41698-024-00501-4 -
BMC Oral Health Jan 2024This study aims to discuss the characteristics and treatment methods of malignant tumors in the parotid region, as well as the therapeutic effects of immediate free flap...
OBJECTIVE
This study aims to discuss the characteristics and treatment methods of malignant tumors in the parotid region, as well as the therapeutic effects of immediate free flap reconstruction of soft tissue for postoperative defects.
MATERIALS AND METHODS
A retrospective review was conducted on 11 cases of soft tissue flap reconstruction for postoperative defects following the resection of malignant tumors in the parotid region. Statistical analysis was performed based on clinical data.
RESULTS
Among the 11 cases of malignant tumors in the parotid region, there were 2 cases of secretory carcinoma (SC) of the salivary gland, 2 cases of squamous cell carcinoma (SCC), 2 cases of carcinosarcoma, 1 case of mucoepidermoid carcinoma (MEC), 1 case of epithelial-myoepithelial carcinoma (EMC), 1 case of salivary duct carcinoma (SDC), 1 case of basal cell carcinoma (BCC), and 1 case of osteosarcoma. Among these cases, 4 were initial diagnoses and 7 were recurrent tumors. The defect repairs involved: 8 cases with anterolateral thigh free flap (ALTF), 2 cases with pectoralis major muscle flaps, and 1 case with forearm flap. The size of the flaps ranged from approximately 1 cm × 3 cm to 7 cm × 15 cm. The recipient vessels included: 4 cases with the facial artery, 4 cases with the superior thyroid artery, and 1 case with the external carotid artery. The ratio of recipient vein anastomosis was: 57% for branches of the internal jugular vein, 29% for the facial vein, and 14% for the external jugular vein. Among the 8 cases that underwent neck lymph node dissection, one case showed lymph node metastasis on pathological examination. In the initial diagnosis cases, 2 cases received postoperative radiotherapy, and 1 case received I seed implantation therapeutic treatment after experiencing two recurrences. Postoperative follow-up revealed that 2 cases underwent reoperation due to local tumor recurrence, and there were 2 cases lost to follow-up. The survival outcomes after treatment included: one case of distant metastasis and one case of death from non-cancerous diseases.
CONCLUSION
Immediate soft tissue flap reconstruction is an important and valuable option to address postoperative defects in patients afflicted with malignant tumors in the parotid region.
Topics: Humans; Skin Transplantation; Parotid Region; Neoplasm Recurrence, Local; Carcinoma, Squamous Cell; Algorithms
PubMed: 38238723
DOI: 10.1186/s12903-024-03872-z