Metastasis Of Breast Carcinoma Research Articles

Double Primary Cancer: Breast Cancer and Gastric Cancer

Introduction: Breast carcinoma is the most prevalent malignancy and the second leading cause of cancer death in women, while multiple primaries are conditions where there is more than one synchronous or metachronous cancer in one individual. Double primary between breast carcinoma and colon cancer is a primary tumor with a high incidence, while breast carcinoma metastasis to the colon is a rare entity except for lobular histotype breast carcinoma. In this case report, a woman with double primary breast cancer is reported. Case Report: A 50-year-old woman came with complaints pain of the entire abdomen since 2 days before go to hospital, worsening when starting to eat, accompanied by nausea. The patient had a history of modified radical mastectomy (MRM) for indications of right breast carcinoma cT3N0M0. In addition, a history of ovarian carcinoma that had undergone chemotherapy was also found. On esophagogastroduodenoscopy examination, a gastric mass was found with ulceration and necrosis and a biopsy showed high-grade neuroendocrine carcinoma and adenocarcinoma. Conclusion: Breast malignancy can be invasive or non-invasive and can undergo metastasis. In addition to metastasis, cancer can also appear in two different places but histologically or morphologically different. This condition is called multiple primaries due to host, lifestyle, and environmental factors.

Spatial Transcriptomic Profiling Reveals Gene Expression Characteristics in Lymph Node-positive Breast Carcinoma.

Studies on the differences in gene expression characteristics according to lymph node metastasis in breast carcinoma are lacking. This study aimed to compare the spatially resolved transcriptomic profiles between node-positive and negative breast carcinomas. Eight patients with breast carcinoma were included, and digital spatial profiling and bioinformatic analysis were conducted to investigate the spatial transcriptomes. In the epithelial compartment, the top two most up-regulated genes were nuclear receptor subfamily 4 group A member 1 (NR4A1) and Jun proto-oncogene, activating protein-1 transcription factor subunit (JUN). The gene ontology (GO) enrichment analysis of the node-positive group revealed a significant up-regulation of genes associated with myeloid differentiation, mononuclear cell differentiation, and hematopoietic regulation. The gene set enrichment analysis (GSEA) revealed significant enrichment of gene sets associated with the regulation of inflammatory cytokines in both the epithelial and stromal compartments of the node-positive group. Our study highlights significant differences in gene expression profiles and spatially resolved transcriptional activities between node-positive and negative breast carcinomas. These findings underscore the importance of developing personalized treatment strategies for lymph node metastasis of breast carcinoma.

Development of in vitro and in vivo c-Met targeted dual-modal nanoprobes for NIR II fluorescent bioimaging and magnetic resonance imaging of breast carcinoma metastasis

Because of the conventional bioimaging methods, including ultrasound and X-ray examinations often lack accuracy and sensitivity in the early diagnosis, as a heterogeneous subtype of breast cancer, it remains an urgent need to develop efficaciously and sensitively diagnostic drivers of triple negative breast cancer (TNBC). The overexpression of c-mesenchymal epithelial transition-factor (c-Met) is associated with the basal subtype of breast carcinoma and linked with decreased survival rate of TNBC patients. Here, we have synthesized a dual-modal nanoprobe with luminescence imaging in the bio-window of near infrared II region (NIR II, 1000–1700) and magnetic resonance imaging (MRI) performances. After c-Met targeting binding protein decoration, this Fe3O4@mSiO2-ICG/cMBP had outstanding size stability and preeminent biocompatibility. Meaningfully, it presented effective TNBC cells recognition in vitro. Besides, after caudal-vein injection of this nanoprobe, both NIR II luminescence imaging and MRI demonstrated that it can more efficiently concentrated in metastatic TNBC tumors in comparison with Fe3O4@mSiO2-ICG and clinical used Gd-DTPA. Meanwhile, the core–shell nanoprobes also showed negligible toxicity in vivo. All results suggested that our cMBP modified nanocomposite could provide a fascinating and efficient non-invasive diagnostic tool for TNBC detection in clinic.

High CD90 Expression is A Predictor of Axillary Nodal Metastasis in Breast Carcinoma

High CD90 Expression is A Predictor of Axillary Nodal Metastasis in Breast Carcinoma

Periarterial or perivenous invasion is an independent indicator of lymph node metastasis in invasive breast carcinoma of no special type

Pathological diagnosis of breast cancer often includes cases of lymph node metastases without lymphatic or lymphovascular invasion by the primary tumor. In this study, to resolve this discrepancy, we designed a sensitive method to detect lymphatic invasion and correlate it with lymph node metastasis. Elastica van Gieson (EVG) staining and D2–40 immunohistochemistry revealed the abundant distribution of lymphatic vessels around blood vessels in the mammary tissue in close proximity to the elastic fibers around the arteries and veins. Based on the histological location of the blood and lymphatic vessels, we hypothesized that, in breast cancer, perivascular invasion is similar to lymphatic invasion and correlates with the presence of lymph node metastasis. Using EVG staining, perivascular invasion was histologically classified into periarterial invasion (periA), perivenous invasion (periV), and periarterial or perivenous invasion (periA/V). We tested our method and compared it to other methods commonly used for identifying lymphatic invasion in 105 patients with invasive breast carcinoma of no special type (IBC-NST) who received minimal preoperative therapy. The correlation between perivascular invasion and lymph node metastasis in these patients was statistically analyzed, including findings related to lymphatic invasion, such as retractile artifacts and perineural invasion. PeriA, periV, and periA/V showed significant correlations with lymph node metastasis. PeriA/V had high sensitivity and negative predictive value. The odds ratio (OR) for periV was significantly high in the univariate analysis, while the ORs for periA/V, retraction artifacts, and perineural invasion were significantly high in both the univariate and multivariate analyses. In particular, periA/V revealed a strong correlation with lymph node metastasis (OR: 61.8). These findings indicate that the IBC-NST periA/V ratio is a sensitive pointer of lymphatic invasion and could be an independent and reliable indicator of lymph node metastasis.

Does 5-ALA Fluorescence Microscopy Improve Complete Resectability in Cerebral/Cerebellar Metastatic Surgery? A Retrospective Data Analysis from a Cranial Center.

(1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and thus to a prolongation of survival; (2) Methods: The following variables have been considered: age, sex, number of metastases, localization, involvement of eloquent area, correlation between fluorescence and primary tumor/subtype, resection, and survival time. The influence on the degree of resection was determined with a control MRI within the first three postoperative days; (3) Results: Brain metastases fluoresced in 57.5% of cases. The highest fluorescence rates of 73.3% were found in breast carcinoma metastases and the histologic subtype adenocarcinoma (68.1%). No correlation between fluorescence behavior and localization, primary tumor, or histological subtype was found. Complete resection was detected in 82.5%, of which 56.1% were fluorescence positive. There was a trend towards improved resectability (increase of 12.1%) and a significantly longer survival time (p = 0.009) in the fluorescence-positive group; (4) Conclusions: 5-ALA-assisted extirpation leads to a more complete resection and longer survival and can therefore represent a low-risk addition to modern surgery for brain metastases.

Breast carcinoma metastasis to the submandibular gland: Clinical, sonographic and pathological findings of a rare entity

Introduction: Metastatic disease to the submandibular gland is a rare phenomenon with limited information available on related imaging findings. Case Presentation: We report a 59-year-old female who presented with a palpable nodule in the right submandibular gland 6 years after treatment for breast carcinoma. Ultrasound findings were concerning for distant metastatic disease from breast cancer recurrence. The histopathological analysis of the biopsied tissue confirmed infiltration of the right submandibular gland with an adenocarcinoma from a breast primary. Discussion: Metastatic spread to the major salivary glands is relatively uncommon with a predilection to the parotid gland owing to its extensive intraglandular lymphatic system. Conversely, metastasis to the submandibular gland, which lacks intraglandular lymph nodes, is rare. Ultrasound is the optimal first-line imaging modality to aid in the assessment of submandibular gland disease. Malignant lesions often appear hypoechoic with heterogenous internal architecture and ill-defined borders. However, some low-grade malignancies, can have apparently benign features particularly when smaller in size. Where a focal submandibular gland lesion is identified and neoplasm is suspected, the early use of ultrasound-guided core biopsy is recommended to improve diagnostic yield for histological assessment. Conclusion: While submandibular metastasis is rare, clinical assessment, sonographic findings and use of core needle biopsy aid in prompt diagnosis and management.

Pigmented cutaneous metastasis of breast carcinoma: florid case with zosteriform distribution

Pigmented cutaneous metastasis of breast carcinoma: florid case with zosteriform distribution

Primary Cutaneous Apocrine Carcinoma: Diagnostic and Management Difficulties of an Uncommon Neoplasm

Primary cutaneous apocrine carcinoma (PCAC) is a rare adnexal neoplasm. Due to its clinical presentation, it can mimic other tumors, especially metastasis. We present a case of primary apocrine carcinoma of the axilla mimicking breast carcinoma metastasis in a 54-year-old woman. The patient presented with a painless, lobed, and erythematous nodule in the left axilla of one year duration. We suspected an adnexal neoplasm but also considered metastasis from breast carcinoma. Histological examination revealed apocrine proliferation. Immunohistochemistry stains of tumor cells were positive for AE1/AE3, and negative for CK7, CK20, p63 and GATA3. Radiological explorations did not reveal any signs of malignancy. Considering all these features, the conclusive diagnosis was primary cutaneous apocrine carcinoma. Treatment was wide excision without adjuvant therapy, and no recurrence was noted. Due to the rarity of this carcinoma, its various clinical presentations, and histological overlaps with breast cancer metastasis, making the diagnosis may be challenging. A comprehensive evaluation of all findings is necessary to rule out other tumors. There is any consensus on the management strategy. The standard treatment is surgical excision, but adjuvant therapies such as radiotherapy or chemotherapy can be proposed in advanced stage disease.

Abstract PO2-25-06: A hybrid breast cancer/mesenchymal stem cell population increases distant metastasis and chemoresistance of metaplastic breast carcinomas

Abstract Background: Metaplastic breast carcinoma is a heterogenous, highly aggressive and chemoresistant subtype of triple negative breast cancer (TNBC) with histological evidence of deregulated differentiation towards non-glandular components including spindle, squamous, and sarcomatoid. The role of the tumor microenvironment in the metastatic behavior and chemotherapy response of metaplastic carcinomas needs investigation to improve patient outcomes. Our lab has generated a model of spindle metaplastic breast carcinomas based on mammary epithelial cell-specific CCN6 knockout (MMTV-Cre;Ccn6fl/fl or CCN6KO). We have recently shown that a subset of TNBC cells engulf mesenchymal stem/stromal cells (MSC) generating a hybrid cell population with metastatic ability, which is detected in breast cancer tissue samples. In this study, we tested the hypothesis that hybrid cells may promote chemoresistant distant metastasis in spindle metaplastic breast carcinomas and that the tumor immune microenvironment may play a role in this function. Methods: Luc-GFP-CCN6KO cells were cultured with DsRED-MSCs for 7 days, yielding >90% of hybrid cells detected by flow cytometry. Hybrids or CCN6KO single cultures (1x10(5) cells) were injected intracardially in FVB/NJ syngeneic immune competent mice (n=20 mice per group). Four days after injection, each group was treated with Paclitaxel (PTX, 10 mg/kg twice a week, i.p.) or PBS control. The metastatic burden was evaluated by bioluminescence imaging twice a week. Mice were euthanized 23 days after heart injections, followed by necropsy and histopathological evaluation of the harvested organs. Results: All mice injected with single cultures of CCN6KO cells or hybrid cells formed distant metastasis. CCN6KO cells were highly invasive and spread to the lungs and lymph nodes in the chest,. We noted that 5 of 20 (25%) mice injected with hybrid cells showed metastasis in the liver (n=3 mice), pancreas (n=1), and abdominal lymph nodes (n=1). PTX treatment significantly reduced metastatic burden in mice injected with CCN6KO single cultures compared to vehicle (p=0.035) but had no effect on the metastatic burden of hybrid cells. Histologically, while the metastasis from CCN6KO cells and hybrids showed similar pathological features, consisting of spindle cancer cells with high grade nuclei and >10 mitoses/10 high power fields, hybrid-derived tumors had abundant infiltration by immune cells, mainly neutrophils, compared to single culture tumors. Conclusion: Our data show that hybrid cancer cell/MSC derived from CCN6KO spindle metaplastic carcinomas have higher ability to disseminate to distant organs, especially in the abdomen, compared to cancer cells. Our data show that hybrid cell-derived metastases have increased immune cell infiltration. We provide evidence that hybrid cells enhance Paclitaxel resistance in a mouse model of metaplastic breast carcinoma. Ongoing studies are aimed at elucidating the role of hybrids in the immune microenvironment of metaplastic breast carcinoma and clinical significance. Citation Format: Ahmad Eido, Maria Gonzalez, Celina Kleer. A hybrid breast cancer/mesenchymal stem cell population increases distant metastasis and chemoresistance of metaplastic breast carcinomas [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-25-06.

Abstract PO1-24-05: EZH2 histone methyltransferase activity promotes spindle metaplastic breast carcinoma metastasis and is induced by CCN6 knockout/b-catenin/TCF axis

Abstract Background: Metaplastic breast carcinomas (mBrCAs) are a highly aggressive subtype of triple negative breast cancer with histological evidence of deregulated differentiation towards non-glandular components. Previous studies have demonstrated that human mBrCA often exhibit activation of differentiation pathways, including canonical Wnt/b-catenin and EZH2-mediated transcriptional repression. Our lab has identified CCN6 as a tumor suppressor in mBrCA. MMTV-Cre;Ccn6fl/fl (CCN6KO) mice develop spindle mBrCAs and CCN6 is reduced/lost in 68% of human mBrCAs. Recently, we have demonstrated that the tumor suppressor function of CCN6 in spindle mBrCA requires activation of Wnt/b-catenin signaling pathway. Here, we tested the hypothesis that CCN6 KO leads to the upregulation of EZH2 histone methyltransferase promoting mBrCA. Furthermore, we investigated the requirement for the activation of the Wnt/b-catenin pathway in this mechanism. Methods: To test the effect of CCN6/b-catenin on EZH2 gene and protein expression we performed IHC, IF, qRT-PCR, ChIP-Seq, RNA-seq, invasion and adhesion assays, EZH2 reporter assay and immunoblots in mBrCA cell lines and MMTV-Cre;Ccn6fl/fl tumors. To investigate the role of CCN6KO-induced b-catenin activation on EZH2 activity and neoplastic functions we employed three independent approaches: i) Expression of a dominant-negative Tcf4 (dnTcf4) rescued with EZH2-WT, dSET and dNLS domain mutants versus vector in MMTV-Cre;Ccn6fl/fl tumor-derived cells; ii) Expression of a constitutively active mutant (S33Y) b-catenin in concert with treatment with recombinant human CCN6 (rhCCN6; 500 ug/ml) versus control; iii) Syngeneic orthotopic mammary tumor transplants of MMTV-Cre;Ccn6fl/fl were used for in vivo rescue experiments with rhCCN6 or BSA. To assess the therapeutic benefit of inhibiting EZH2 methyltransferase activity, MMTV-Cre;Ccn6fl/fl tumor cells (CCN6KO cells) were implanted orthotopically or intracardially in FVB mice, followed by treatment with EPZ-6438 (a selective EZH2 methyltransferase inhibitor) or vehicle. We tested CCN6, b-catenin, and EZH2 expression by IHC in a cohort of 27 human mBrCA tumor samples. Results: CCN6KO-induced b-catenin/TCF activation mediates EZH2 transcriptional upregulation and the deposition of repressive H3K27me3 in spindle mBrCAs. We found that the invasion program triggered by CCN6KO-induced Wnt/b-catenin requires EZH2 catalytic activity as WT-EZH2 (but not dSET-EZH2) rescued the reduced invasion of CCN6KO-dnTcf4 cells. RNA-seq and 3H3K27 ChIP-seq of CCN6KO-dnTcf4 cells transduced with EZH2-WT or dSET-EZH2 identify specific CCN6KO-b-catenin/Tcf targets that require EZH2 transcriptional repressor function. In vivo, administration of CCN6 protein to MMTV-Cre;Ccn6fl/fl tumor transplants reduces tumor growth and nuclear b-catenin, EZH2 and 3H3K27 in the tumors. Pharmacologic inhibition of EZH2 reduces the growth and metastasis of CCN6KO mBrCA tumors and improves survival. We identify a subset of human spindle mBrCA (54%) that display a CCN6Low/nuclear b-cat/EZH2High phenotype. Conclusion: We found a critical role for EZH2 activation in CCN6-deficient mBrCA tumor phenotypes via b-catenin/TCF Wnt canonical signaling. We demonstrate the effectiveness of pharmacological inhibition of EZH2 methyltransferase activity in reducing primary tumor growth and distant metastasis in mouse models of spindle mBrCA. In clinical samples, low CCN6 is significantly associated with activated b-catenin and high EZH2 in spindle mBrCAs compared to other subtypes. These data reveal a novel tumor suppressor mechanism of CCN6 and provide compelling evidence supporting the potential therapeutic value of CCN6 restoration, b-catenin or EZH2 inhibition as promising approaches for the treatment of spindle mBrCAs. Citation Format: Maria Gonzalez, Ahmad Eido, GIUSEPPINA AUGIMERI, Celina Kleer. EZH2 histone methyltransferase activity promotes spindle metaplastic breast carcinoma metastasis and is induced by CCN6 knockout/b-catenin/TCF axis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-24-05.

Nuclear localization of heparanase 2 (Hpa2) attenuates breast carcinoma growth and metastasis

Unlike the intense research effort devoted to exploring the significance of heparanase in cancer, very little attention was given to Hpa2, a close homolog of heparanase. Here, we explored the role of Hpa2 in breast cancer. Unexpectedly, we found that patients endowed with high levels of Hpa2 exhibited a higher incidence of tumor metastasis and survived less than patients with low levels of Hpa2. Immunohistochemical examination revealed that in normal breast tissue, Hpa2 localizes primarily in the cell nucleus. In striking contrast, in breast carcinoma, Hpa2 expression is not only decreased but also loses its nuclear localization and appears diffuse in the cell cytoplasm. Importantly, breast cancer patients in which nuclear localization of Hpa2 is retained exhibited reduced lymph-node metastasis, suggesting that nuclear localization of Hpa2 plays a protective role in breast cancer progression. To examine this possibility, we engineered a gene construct that directs Hpa2 to the cell nucleus (Hpa2-Nuc). Notably, overexpression of Hpa2 in breast carcinoma cells resulted in bigger tumors, whereas targeting Hpa2 to the cell nucleus attenuated tumor growth and tumor metastasis. RNAseq analysis was performed to reveal differentially expressed genes (DEG) in Hpa2-Nuc tumors vs. control. The analysis revealed, among others, decreased expression of genes associated with the hallmark of Kras, beta-catenin, and TNF-alpha (via NFkB) signaling. Our results imply that nuclear localization of Hpa2 prominently regulates gene transcription, resulting in attenuation of breast tumorigenesis. Thus, nuclear Hpa2 may be used as a predictive parameter in personalized medicine for breast cancer patients.

Hoof beats could mean zebras: A rare late metastasis of breast carcinoma in the rectum

Breast cancer metastasis is most commonly observed in bone, lung, liver, and brain and is rarely observed in the gastrointestinal tract (GI). In rarer cases, GI metastasis reaches the rectum and generally presents as late metastasis. The type of breast cancer usually associated with GI metastasis is invasive lobular carcinoma; however, few case reports also show their association with invasive ductal carcinoma (IDC). Here, we report a case that unfortunately is a coalescence of all these atypical events, with metastatic rectal linitis plastica (RLP) of the breast, 15 years after the treatment of the primary tumor, originating from IDC. This is the first case report from India, reporting the late metastatic presentation of breast cancer as RLP. The report emphasizes the need to correlate persistent GI symptoms to breast cancer history; however, late the presentation may be.

Nanomedicine Redefining Cancer Therapeutics: The Evolution of Precision Drug Delivery Systems

With the advent of nanomedicines including drug delivery carriers such as nanoparticles, liposomes, nanoemulsions, and micelles, there has been a paradigm shift in the sphere of cancer treatment. These nano-biosystems have been the focus of scientific research in recent years due to their biocompatibility, low toxicity, higher retention time, bioavailability and higher targeted efficiency as compared to conventional therapeutics such as chemotherapy, radiotherapy and immunotherapy. These conventional therapies not only target cancerous cells but negatively affect neighboring health cells as well comprising the individuals’ immune health. Therefore, nanomaterials have been considered the foremost strategy to combat different types of cancer. To facilitate delivery and provide a “stealthy character” to nanomaterials, biomimetic (cell-derived) surface coatings and encapsulations have been developed. Red blood cell mimetic nanoparticles have been designed to successfully inhibit the growth and metastasis of breast carcinoma. Similarly, HeLa cell membrane-derived vesicles of GdTPP/ZnTPP porphyrin nanocomposites have been utilized for photodynamic therapy (PDT) for cervical carcinoma [1]. In addition, ferritin-based and vault-protein nanocarriers have been designed using recombinant engineering techniques to overcome the barriers of multidrug resistance and in-vivo drug delivery reducing immune response and increasing the effectiveness of anticancerous drugs. These functionalized nanocarriers have been reported against glioma, melanoma, hepatocarcinoma, adenocarcinoma and lung cancer [2]. A considerable number of nanomedicines have passed clinical trials and been approved for commercial use by various regulatory organizations. The most recent being the NanoTherm, an EMA-approved nanomedicine for glioblastoma, prostate cancer, and pancreatic cancer. It is a superparamagnetic iron oxide nanoparticle covered with aminosilane [3]. With precision, efficacy, and promise for both patients and clinicians, nanomedicine is a sign of a new era in cancer therapies. Harnessing the potential of nanomedicine demands teamwork, innovation, and transforming ground-breaking research into game-changing clinical applications as we navigate this rapidly changing landscape. With the goal of bringing targeted, personalized cancer treatments closer to reality, this editorial seeks to highlight the unmatched potential of nanomedicine in transforming drug delivery paradigms. 

Orbit: A Window to Systemic Pathology. Breast Carcinoma Metastases

Orbit: A Window to Systemic Pathology. Breast Carcinoma Metastases

Tumor to Tumor Metastasis of Breast Cancer to Pheochromocytoma in a 77 Year Old Man

Abstract Introduction/Objective Male breast cancer is rare, accounting for less than 1% of all breast cancer diagnoses. The most common sites for breast cancer metastasis include bone, lung, liver and brain. Tumor-to-tumor metastasis is an unusual phenomenon where one distinct malignancy is present within the substance of another independent tumor. We present a case of a 77-year-old man with a left pheochromocytoma and a tumor to tumor metastasis (TTM) from breast cancer. To our knowledge, this is the first case of a TTM from a breast cancer to a pheochromocytoma in a man. Methods/Case Report The patient is a 77 year old man with a past medical history of a right pheochromocytoma resected 20 years ago and a recently diagnosed right breast cancer. PET-CT identified a left adrenal mass. Microscopic sections of the left adrenal gland showed nests of neoplastic cells arranged in a “zellballen” pattern. Adjacent to the neoplasm was a sheet of atypical epithelioid cells with increased nuclear to cytoplasmic ratios and frequent mitoses. Immunohistochemical stains were performed, and the nests of neoplastic cells with the zellballen pattern were positive for chromogranin and synaptophysin and negative for CAM5.2. A focus of the adrenal neoplasm was negative for these stains but stained positively for CAM5.2. Due to patient’s history, additional immunohistochemical stains were performed, staining with ER, CK7, GATA3, and mammaglobin was observed. These findings were interpreted as a tumor-to tumor metastasis of metastatic breast carcinoma to pheochromocytoma in the left adrenal gland. Results (if a Case Study enter NA) NA Conclusion Tumor-to-tumor metastasis (TTM) is an unusual phenomenon in which a primary tumor metastasizes into another tumor. Lung and breast carcinomas are the most common metastatic donors, while renal cell carcinoma and meningioma are the most common malignant and benign recipients. In patients with TTM, proper use of immunohistochemical stains and patient’s history can aid in the diagnosis of the distinct tumors.

Primary metaplastic breast carcinoma or breast metastasis of a poorly differentiated squamous cell carcinoma from the lung? Distinction not always clear

Diagnosing primary triple-negative breast cancer (TNBC) with lung metastases or primary TTF1negative lung carcinoma can be difficult due to lack of a TNBC standard immunoprofile.We report a rare case of a woman with an age range between 50 and 55 years, who presented with a mass of the left breast evolving for 2 months. The core needle biopsy concluded to a TNBC. Complete staging with a thoraco-abdomino-pelvic and cerebral computed tomography revealed a huge lung mass associated with laterotracheal and subcarineal adenomegaly next to spinal lytic lesions and bilateral adrenal masses consisting with metastasis. The lung biopsy revealed a poorly differentiated squamous cell carcinoma. The patient was then scheduled to chemotherapy.Pathological and immunohistochemistry studies are limited to establish the formal diagnosis between primary metaplastic carcinoma that metastasize to the lung and primary lung poorly differentiated squamous cell carcinoma. Confrontation with radiology and clinical presentation is highly important to resolve the problem.

Breast Carcinoma and Tuberculosis in Axillary Lymph Nodes: A Case Report

The coexistence of tuberculosis with axillary lymph node metastases in breast carcinoma is rare. Axillary lymph node metastasis is the most important factor in the staging of breast carcinoma, this can mimic or complicate the staging of a malignant disease. Dual organ pathology can lead to interpretation difficulties and inappropriate treatment of tuberculosis as well as breast carcinoma. We report an observation of infiltrating carcinoma of the non-specific type of the breast in woman aged 39, where tuberculosis was found in the axillary lymph nodes in addition to metastases. The possible and simultaneous occurrence of breast carcinoma and tuberculosis should be mentioned in order to avoid difficulties of interpretation and allow adequate management of axillary tuberculous lymphadenitis and breast carcinoma.

CRISPR-Cas9 based knockout of S100A8 in mammary epithelial cells enhances cell proliferation and triggers oncogenic transformation via the PI3K-Akt pathway: Insights from a deep proteomic analysis

S100A8 is a calcium-binding protein with multiple functions, including being a chemoattractant for phagocytes and playing a key role in the inflammatory response. Its expression has been shown to influence epithelial-mesenchymal transition (EMT) and metastasis in colorectal cancer. However, the role of S100A8 in cell proliferation and differentiation remains unknown. In this study, we used the CRISPR-Cas9 system to knock out S100A8 in healthy mammary epithelial cells and investigated the resulting changes in proteome profiling and signaling pathways. Our results showed that S100A8 knockout led to an increase in cell proliferation and migration, reduced cell-cell adhesion, and increased apoptosis compared to wildtype cells. Proteomics data indicated that S100A8 significantly affects cell cycle progression, cell proliferation, and cell survival through the PI3K-Akt pathway. Furthermore, our findings suggest that S100A8 function is associated with Pten expression, a negative regulator of the PI3K-Akt pathway. These results indicate that S100A8 dysregulation in healthy cells can lead to altered cellular physiology and higher proliferation, similar to cancerous growth. Therefore, maintaining S100A8 expression is critical for preserving healthy cell physiology. This study provides novel insights into the role of S100A8 in cell proliferation and differentiation and its potential relevance to cancer biology. SignificanceThe study suggests that maintaining S100A8 expression is critical for preserving healthy cell physiology, and dysregulation of S100A8 in healthy cells can lead to altered cellular physiology and higher proliferation, similar to cancerous growth. Therefore, targeting the PI3K-Akt pathway or regulating Pten expression, a negative regulator of the PI3K-Akt pathway, may be potential strategies for cancer treatment by controlling S100A8 dysregulation. Additionally, S100A8 and S100A9 have been shown to promote metastasis of breast carcinoma by forming a metastatic milieu. However, the differential expression of S100A8 in tumors and its dual effects of antitumor and protumor make the relationship between S100A8 and tumors complicated. Currently, most research focuses on the function of S100A8 as a secretory protein in the microenvironment of tumors, and its function inside healthy cells without forming dimers remains unclear. Furthermore, the study provides insight into the role of S100A8 in cell proliferation and differentiation, which may have implications for other diseases beyond cancer. The functional role of S100A8 in normal mammary epithelial cells remains completely uncertain. Therefore, the objective of this study is to investigate the function of S100A8 on proliferation in mammary epithelial cells after its deletion and to elucidate the underlying proteins involved in downstream signaling. Our findings indicate that the deletion of S100A8 leads to excessive proliferation in normal mammary epithelial cells, reduces apoptosis, and affects cell-cell adhesion molecules required for cellular communication, resulting in a cancer-like phenotype.

Berberine inhibits breast carcinoma proliferation and metastasis under hypoxic microenvironment involving gut microbiota and endogenous metabolites

A potential role of berberine, a benzyl isoquinoline alkaloid, in cancer therapy is apparent. Its underlying mechanisms of berberine against breast carcinoma under hypoxia have not been elucidated. We focused on the doubt how berberine restrains breast carcinoma under hypoxia in vitro and in vivo. A molecular analysis of the microbiome via 16 S rDNA gene sequencing of DNA from mouse faeces confirmed that the abundances and diversity of gut microbiota were significantly altered in 4T1/Luc mice with higher survival rate following berberine treatment. A metabolome analysis liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS) revealed that berberine regulated various endogenous metabolites, especially L-palmitoylcarnitine. Furthermore, the cytotoxicity of berberine was investigated in MDA-MB-231, MCF-7, and 4T1 cells. In vitro to simulate under hypoxic environment, MTT assay showed that berberine inhibited the proliferation of MDA-MB-231, MCF-7, and 4T1 cells with IC50 values of 4.14 ± 0.35 μM, 26.53 ± 3.12 μM and 11.62 ± 1.44 μM, respectively. Wound healing and trans-well invasion studies revealed that berberine inhibited the invasion and migration of breast cancer cells. RT-qPCR analysis shed light that berberine reduced the expression of hypoxia-inducible factor-1α (HIF-1α) gene. Immunofluorescence and western blot demonstrated that berberine decreased the expression of E-cadherin and HIF-1α protein. Taken together, these results provide evidence that berberine efficiently suppresses breast carcinoma growth and metastasis in a hypoxic microenvironment, highlighting the potential of berberine as a promising anti-neoplastic agent to combat breast carcinoma.