Transcriptomic analysis identifies enrichment of cAMP/PKA/CREB signaling in invasive lobular breast cancer.

OBJECTIVE: Invasive lobular breast cancer (ILC) is the most common special type of breast cancer and has unique clinicopathological and molecular hallmarks that differentiate it from the more common invasive carcinoma-no special type (NST). Despite these differences, ILC and NST are treated as a single entity and there is a lack of ILC-targeted therapies. To fill this gap, we sought to identify novel molecular alterations in ILC that could be exploited for targeted therapies. METHODS: Differential gene expression and Geneset Enrichment and Variation analyses were performed on RNA-seq data from three large public breast cancer databases-the Sweden Cancerome Analysis Network-Breast (SCAN-B; luminal A ILC N = 263, luminal A NST N = 1162), The Cancer Genome Atlas (TCGA; luminal A ILC N = 157, luminal A NST N = 307) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; luminal A ILC N = 65, luminal A NST N = 533). Pathways enriched in overlapping differentially expressed genes from these datasets were clustered using Jaccard similarity to identify pathways enriched in ILC. The cAMP/PKA/CREB signaling was studied in ILC, ILC-like and NST cell lines and patient-derived organoids (PDOs) using forskolin, an activator of the pathway. RESULTS: Clinicopathological features of patients with ILC and NST in SCAN-B were similar to prior population-based studies. There was a consistent pattern of up-regulation of cAMP/PKA/CREB related signaling in ILC compared to NST in SCAN-B, TCGA and METABRIC. Treatment with forskolin resulted in a greater increase in phospho-CREB in ILC cell lines and organoids than NST. CRISPR deletion of CDH1 in NST cell lines did not alter response of cells to forskolin as measured by phospho-CREB. Forskolin treatment caused growth inhibition in ILC and NST, with ILC cell lines being more sensitive to forskolin-mediated growth inhibition. CONCLUSION: In three separate datasets, cAMP/PKA/CREB signaling was identified to be higher in ILC than NST. This in silico finding was validated in cell line and organoid models. Loss of CDH1 was not sufficient to mediate this phenotype. Future studies should investigate the mechanisms for differential cAMP/PKA/CREB signaling and the potential for therapeutic targeting in patients with ILC.

Tumour budding in invasive breast carcinoma of no special type - relationship with clinicopathological parameters.

Each breast cancer is a heterogeneous tumour with different clinicopathological feature, and thus they all have different prognoses. Tumour budding (TB), considered as the first step in tumour metastasis, is the most critical factor for poor prognosis and is associated with the epithelial-mesenchymal transition (EMT). Tumour budding and its clinicopathological features in invasive breast carcinoma of no special type (NST). Patients who underwent surgery for invasive breast carcinoma (NST) between January 2018 and 2022 were retrospectively reviewed from the database, haematoxylin and eosin-stained slides were retrieved and reevaluated. The study included 200 patients. The mean number of TB was 12.8 ±9.6. The number of TB was significantly lower in patients who underwent neoadjuvant chemotherapy treatment ( p = 0.002). There was a weak positive correlation between TB count and tumour size ( r = 0.177). Triple-negative patients had significantly lower TB counts ( p = 0.001). No significant difference was observed between histological grade, nuclear grade, presence of ductal carcinoma in situ , stromal tumour-infiltrating lymphocytes, perineural invasion, lymph node metastasis, and number of TB ( p > 0.05). The number of TB was higher in oestrogen receptor positive tumours ( p = 0.015). There were more TB in patients with angiolymphatic invasion, which supports the pathophysiological relationship between tumour budding, metastasis, and EMT. Clarification of the mechanism of TB with more studies is promising in terms of treatment options.

Joint EANM-SNMMI guideline on the role of 2-[18F]FDG PET/CT in no special type breast cancer : (endorsed by the ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA).

INTRODUCTION: There is much literature about the role of 2-[18F]FDG PET/CT in patients with breast cancer (BC). However, there exists no international guideline with involvement of the nuclear medicine societies about this subject. PURPOSE: To provide an organized, international, state-of-the-art, and multidisciplinary guideline, led by experts of two nuclear medicine societies (EANM and SNMMI) and representation of important societies in the field of BC (ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA). METHODS: Literature review and expert discussion were performed with the aim of collecting updated information regarding the role of 2-[18F]FDG PET/CT in patients with no special type (NST) BC and summarizing its indications according to scientific evidence. Recommendations were scored according to the National Institute for Health and Care Excellence (NICE) criteria. RESULTS: Quantitative PET features (SUV, MTV, TLG) are valuable prognostic parameters. In baseline staging, 2-[18F]FDG PET/CT plays a role from stage IIB through stage IV. When assessing response to therapy, 2-[18F]FDG PET/CT should be performed on certified scanners, and reported either according to PERCIST, EORTC PET, or EANM immunotherapy response criteria, as appropriate. 2-[18F]FDG PET/CT may be useful to assess early metabolic response, particularly in non-metastatic triple-negative and HER2+ tumours. 2-[18F]FDG PET/CT is useful to detect the site and extent of recurrence when conventional imaging methods are equivocal and when there is clinical and/or laboratorial suspicion of relapse. Recent developments are promising. CONCLUSION: 2-[18F]FDG PET/CT is extremely useful in BC management, as supported by extensive evidence of its utility compared to other imaging modalities in several clinical scenarios.

Retrospective cohort study on the bilateral occurrence of invasive lobular breast cancer.

OBJECTIVE: Invasive lobular carcinoma (ILC) is the second most common histological subtype of invasive breast cancer, following the no special type (NST) invasive carcinoma. It has historically been assumed that ILC occurs bilaterally in 20-29 % of cases, which has influenced the inclusion of MRI in the standard workup of ILC according to European guidelines. However, challenging this long-held belief regarding the bilateral occurrence of ILC opens up the possibility of revising the guidelines and using MRI only for more specific indications. This study aims to evaluate whether the previously reported high percentage of bilaterality still holds true and to question the added value of MRI in the standard workup of ILC. STUDY DESIGN: A retrospective cohort study was conducted following approval from the institutional review board (EC 21/18/249) at Antwerp University Hospital (UZA). The cohort comprised female patients of all ages who had been diagnosed with either ILC or NST invasive carcinoma and had sought consultation at the UZA breast clinic. A comprehensive database was established to collect information on patient characteristics, imaging, and pathology. RESULTS: A total of 271 patients with ILC were included in the study, with incidence dates ranging from 01/01/2007 to 01/01/2023. Among these patients, a synchronous bilateral ILC lesion was observed in 1.85 % (5/271) of cases. This proportion is significantly lower than the reported percentage of patients with a bilateral lesion in the literature population, which stands at 4.95 %. The reference group consisted of 809 patients with NST invasive carcinoma, with incidence dates ranging from 01/01/2017 to 01/01/2023. In the control group, a synchronous bilateral NST lesion was observed in 3.96 % (32/809) of cases. There is no significant difference in the bilaterality rates between the group of ILC patients and the group of NST patients. Furthermore, MRI did not detect any histopathologically confirmed contralateral ILC lesion that had not already been detected by mammography or ultrasound. CONCLUSIONS: The study results indicate a lower occurrence of bilateral ILC than previously assumed. Additionally, the incidence of synchronous bilateral lesions in ILC patients is not higher compared to patients with NST invasive carcinoma. Performing an MRI does not provide additional value in detecting bilateral carcinomas in ILC. Consequently, it is recommended that the current European guidelines be reassessed, and the indications for undergoing an MRI should be adjusted accordingly.

Comparison of clinical characteristics and outcomes in primary neuroendocrine breast carcinoma versus invasive ductal carcinoma.

Background: Neuroendocrine breast carcinoma (NECB) is a rare, special histologic type of breast cancer. There are some small sample studies on the clinical outcomes of NECB patients, which are worthy of further discussion. Methods: We conducted a retrospective case-control study of clinical characteristics and outcomes among patients with primary NECB versus invasive carcinoma of no special type (NST) between November 2004 and November 2017 in the Peking Union Medical College Hospital, Beijing. NST patients were strictly matched 1:4 during the same period based on the TNM stage. Statistical comparisons were performed to determine the differences in survival between NST and NECB patients and to identify clinical factors that correlate with prognosis. Results: A total of 121 participants affected by primary NECB were included in our analysis from November 2004 to November 2017. Elderly persons (>60 years of age) were more likely to have primary NECB than young persons (p=0.001). In addition, primary NECB patients had significantly higher odds of having tumors 2-5 cm (36.5%) and >5 cm (6.1%) in size than NST patients. Despite a significant difference in tumor size, the proportion of patients with lymph node metastases showed no difference between the two groups (p=0.021). In addition, the rate of patients with ER-negative tumors in the NECB group (4.2%) was significantly lower than that in the primary NST group (29.8%). Significant differences were noted in the PR-negative (13.3% versus 36.6%, P<0.001) and HER2-negative (90.5% versus 76.4%, P=0.001) expression statuses among these patients. Of 121 primary NECB patients, 11 (9.1%) experienced relapses during the follow-up period. We found that tumor size was an independent risk factor for relapse. For hormone receptors on tumor cells, ER-positive breast cancer patients had significantly lower odds of relapse than receptor-negative patients. Conclusions: Our data demonstrate no significant difference in mortality and relapse between the primary NECB and NST groups. The tumor size in the primary NECB group was significantly larger than that in the NST group. In addition, the absence of ER independently increased the relapse rate for breast carcinoma patients.

Metastases of primary mixed no-special type and lobular breast cancer display an exclusive lobular histology.

Primary tumors with a mixed invasive breast carcinoma of no-special type (IBC-NST) and invasive lobular cancer (ILC) histology are present in approximately five percent of all patients with breast cancer and are understudied at the metastatic level. Here, we characterized the histology of metastases from two patients with primary mixed IBC-NST/ILC from the postmortem tissue donation program UPTIDER (NCT04531696). The 14 and 43 metastatic lesions collected at autopsy had morphological features and E-cadherin staining patterns consistent with pure ILC. While our findings still require further validation, they may challenge current clinical practice and imaging modalities used in these patients.

Effect of histological breast cancer subtypes invasive lobular versus non-special type on survival in early intermediate-to-high-risk breast carcinoma: results from the SUCCESS trials.

BACKGROUND: Invasive lobular breast carcinomas (ILC) have different histological features compared to non-special type carcinomas (NST), but the effect of histological subtypes on survival is controversial. In this study, we compared clinicopathological characteristics and outcomes between ILC and NST based on a large pooled data set from three adjuvant breast cancer trials (SUCCESS A, B, and C) and investigated a potential differential effect of recurrence risk related to nodal stage on survival. METHODS: From 2005 to 2017, the large randomized controlled SUCCESS A, B, and C trials enrolled 8190 patients with primary, intermediate-to-high-risk breast carcinoma. All patients received adjuvant chemotherapy, and endocrine and/or HER2-targeted treatment was given where appropriate. Survival outcomes in terms of disease-free survival (DFS), overall survival (OS), breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) were estimated using the Kaplan-Meier method and analyzed using log-rank tests as well as univariable and adjusted multivariable Cox regression models. RESULTS: In the SUCCESS trials, 6284 patients had NST and 952 had ILC. The median follow-up time was 64 months. ILC patients were older, more likely to receive mastectomy, and more likely to have larger tumor sizes, lymph node infiltration, hormone receptor-positive, HER2neu-negative, and luminal A-like tumors than NST patients. In the overall cohort, no significant differences between ILC and NST were detectable regarding the four survival endpoints, with hazard ratios obtained in adjusted multivariable cox regressions of 0.96 (95% CI 0.77-1.21, p = 0.743) for DFS, 1.13 (95% CI 0.85-1.50, p = 0.414) for OS, 1.21 (95% CI 0.89-1.66, p = 0.229) for BCSS, and 0.95 (95% CI 0.73-1.24, p = 0.689) for DDFS. However, a differential effect of nodal stage on survival was observed, with better survival for ILC patients with pN0/pN1 tumors and worse survival for ILC patients with pN2/pN3 tumors compared to NST patients. CONCLUSIONS: Our results revealed that ILC was associated with worse survival compared to NST for patients at high risk of recurrence due to advanced lymph node infiltration. These findings should be taken into account for treatment decisions and monitoring.

Metastatic Breast Cancer Presenting as Acute Appendicitis: A Rare Case Study and Review of Current Knowledge.

This manuscript discusses a rare case of acute appendicitis caused by metastasis from invasive breast carcinoma of no special type in a 70-year-old female previously diagnosed with breast cancer. It delves into the diagnostic challenges and management complexities of such unusual clinical presentations. The paper includes an analysis of 19 documented cases, enriching the understanding of metastatic patterns and treatment strategies in breast cancer. It underlines the importance of considering a history of malignancy when diagnosing acute abdominal conditions and emphasizes a comprehensive approach in interpreting diagnostic imaging in patients with past oncological issues to effectively manage metastatic breast cancer exhibiting atypical manifestations.

Predictive Potential of RNA Polymerase B (II) Subunit 1 (RPB1) Cytoplasmic Aggregation for Neoadjuvant Chemotherapy Failure.

We aimed to investigate the contribution of co-translational protein aggregation to the chemotherapy resistance of tumor cells. Increased co-translational protein aggregation reflects altered translation regulation that may have the potential to buffer transcription under genotoxic stress. As an indicator for such an event, we followed the cytoplasmic aggregation of RPB1, the aggregation-prone largest subunit of RNA polymerase II, in biopsy samples taken from patients with invasive carcinoma of no special type. RPB1 frequently aggregates co-translationally in the absence of proper HSP90 chaperone function or in ribosome mutant cells as revealed formerly in yeast. We found that cytoplasmic foci of RPB1 occur in larger sizes in tumors that showed no regression after therapy. Based on these results, we propose that monitoring the cytoplasmic aggregation of RPB1 may be suitable for determining-from biopsy samples taken before treatment-the effectiveness of neoadjuvant chemotherapy.

Invasive breast carcinoma of no special type with medullary pattern: A case report at a tertiary facility in Tanzania.

Key Clinical Message: Describes a rare form of invasive breast cancer of no special type.Not a distinct morphological subtype.Characterized by dense lymphoid infiltrate, syncytial growth, pushing borders, and cells with high-grade nuclei.Clinically aggressive but carries a better prognosis than other more frequent invasive breast carcinomas. Abstract: Invasive breast carcinoma of no special type with medullary pattern (BCNST-MP) is a rare form of breast tumor, accounting for less than 5% of all invasive breast carcinomas. Its diagnosis is based on histologic criteria. Historically, this tumor was known as medullary carcinoma. Poor morphological reproducibility led to re-classification. Despite having an aggressive biological behavior, these tumors usually carry a better prognosis compared with other more frequent forms of invasive breast carcinomas. Herein, we present a case of BCNST-MP in a 58-year-old African female, successfully treated in our institution through chemo-radiation, hormonal therapy and surgery.

Perineural Invasion Predicts Unfavorable Prognosis in Patients With Invasive Breast Cancer.

BACKGROUND/AIM: Perineural invasion (PNI) is a poor prognostic factor in a variety of cancers. However, the frequency of PNI in invasive breast carcinoma varies among studies, and the prognostic significance of PNI remains unclear. Therefore, we aimed to explore the prognostic value of PNI in breast cancer patients. PATIENTS AND METHODS: The cohort included 191 consecutive female patients who underwent surgical resection of invasive carcinoma of no special type (NOS). The correlations between PNI and clinicopathological characteristics including prognosis were investigated. RESULTS: The frequency of PNI was 14.1% (27/191) and the PNI-positive status was significantly correlated with large pathological tumor size (p=0.005), lymph node metastasis (p=0.001), and lymphatic invasion (p=0.009). The log-rank test showed that PNI-positive patients had shorter distant metastasis-free survival (DMFS) (p=0.002) and disease-specific survival (DSS) (p<0.001). According to the multivariate analysis, PNI had a significant adverse effect on DMFS (p=0.037) and DSS (p=0.003). CONCLUSION: PNI could be used as an independent poor prognostic indicator in patients with invasive breast carcinoma.

Recognizing invasive breast carcinoma of no special type with medullary pattern.

Invasive breast carcinoma of no special type (IBC-NST) with medullary pattern is an uncommon histologic type of invasive breast carcinoma. It is associated with high-grade, poorly differentiated tumor cells that form large sheets of irregular confluent tumor cells associated with a prominent lymphocytic infiltrate. Patients with IBC-NST with medullary pattern are often postmenopausal women with a high body mass index and multiparity. We report the case of a 71-year-old woman who presented for routine screening mammography and breast mass suspicious for malignancy, initially thought to be invasive ductal carcinoma with an associated prominent lymphoid infiltrate. However, it was ultimately diagnosed as IBC-NST with medullary pattern, and radiologic imaging (particularly ultrasound and mammography) along with pathology review were critical in making the diagnosis. We make the case of the importance of radiographic imaging in diagnosing this condition, as the prognosis of IBC-NST with medullary pattern is typically more favorable compared to IBC-NST.

Transcriptomic alterations underlying metaplasia into specific metaplastic components in metaplastic breast carcinoma.

BACKGROUND: Metaplastic breast carcinoma (MpBC) typically consists of carcinoma of no special type (NST) with various metaplastic components. Although previous transcriptomic and proteomic studies have reported subtype-related heterogeneity, the intracase transcriptomic alterations between metaplastic components and paired NST components, which are critical for understanding the pathogenesis underlying the metaplastic processes, remain unclear. METHODS: Fifty-nine NST components and paired metaplastic components (spindle carcinomatous [SPS], matrix-producing, rhabdoid [RHA], and squamous carcinomatous [SQC] components) were microdissected from specimens obtained from 27 patients with MpBC for gene expression profiling using the NanoString Breast Cancer 360 Panel on a NanoString nCounter FLEX platform. BC360-defined signatures were scored using nSolver software. RESULTS: Hierarchical clustering and principal component analysis revealed a heterogeneous gene expression profile (GEP) corresponding to the NST components, but the GEP of metaplastic components exhibited subtype dependence. Compared with the paired NST components, the SPS components demonstrated the upregulation of genes related to stem cells and epithelial-mesenchymal transition and displayed enrichment in claudin-low and macrophage signatures. Despite certain overlaps in the enriched functions and signatures between the RHA and SPS components, the specific differentially expressed genes differed. We observed the RHA-specific upregulation of genes associated with vascular endothelial growth factor signaling. The chondroid matrix-producing components demonstrated the upregulation of hypoxia-related genes and the downregulation of the immune-related MHC2 signature and the TIGIT gene. In the SQC components, TGF-ß and genes associated with cell adhesion were upregulated. The differentially expressed genes among metaplastic components in the 22 MpBC cases with one or predominantly one metaplastic component clustered paired NST samples into clusters with correlation with their associated metaplastic types. These genes could be used to separate the 31 metaplastic components according to respective metaplastic types with an accuracy of 74.2%, suggesting that intrinsic signatures of NST may determine paired metaplastic type. Finally, the EMT activity and stem cell traits in the NST components were correlated with specimens displaying lymph node metastasis. CONCLUSIONS: We presented the distinct transcriptomic alterations underlying metaplasia into specific metaplastic components in MpBCs, which contributes to the understanding of the pathogenesis underlying morphologically distinct metaplasia in MpBCs.

Revisiting Metaplastic Carcinoma of Breast: An Emphasis on the Clinico-pathological and Immunohistochemical Variables Analyzed at a Tertiary Cancer Centre in South India.

Background & Objective: Metaplastic carcinoma is a diverse variant of invasive breast carcinomas (IBC) characterized by dedifferentiation of malignant cells towards squamous and/or mesenchymal elements. It accounts for 0.3-1.2% of all IBC. These tumors are typically triple-negative by hormonal profiling with a high proliferation index and a dismal prognosis. Lymph node metastasis is an unusual feature in metaplastic carcinoma. Methods: The present study analyses 30 cases (26 cases of modified radical mastectomy and 4 cases of lumpectomy) of metaplastic carcinoma over 2018-2020 (3 years). Four oncopathologists reviewed routine histopathologic and immunohistochemical-stained slides. The clinical details were collected from the Medical Records Department of the Cancer Institute. Results: A total of 20 (66.67%) cases were patients >50 years of age, 21(70%) out of which were diagnosed as invasive carcinoma, grade 3 according to the Nottingham histological score. Five (16.7%) cases presented with lymph node metastasis. While immunohistochemically 28 (93.3%) cases were triple-negativeCK5/6, P63, EGFR, and Ki-67 (more than 40%) positivity was noted in 25 (83.3%) , 26 (86,7%) , 20 (66.7%), and 25 (83.3%) cases, respectively. Conclusion: Metaplastic carcinoma is characteristically triple-negative breast malignancies (TNBC) exhibiting a high Ki-67 index and a lower rate of lymph node metastasis. CK5/6, p63, and EGFR are pertinent immunohistochemical markers that may aid in diagnosis. However, those markers are non-specific for the disease and morphologic features are always the key to diagnosis of the process.

Molecular subtypes of invasive breast carcinoma of no special type, their correlation with histopathological features, Ki 67 index and tumor budding: A retrospective comparative study.

Context: Tumor budding (TB), poorly differentiated clusters (PDCs), and Ki 67 index are proven adverse prognostic factors in breast carcinoma. Though the relation of Ki 67 index with molecular subtypes of breast carcinoma have been extensively studied, there is very limited information on the role of TB and PDCs. Aims: To grade TB, PDCs, and Ki 67 index and assess histological features and relationship of all these with molecular subtypes of invasive breast carcinoma of no special type. Methods and Material: Retrospective study of 148 cases from 1/1/2019 to 30/12/2019. Division of molecular groups - Luminal A, Luminal B, Her2 neu positive, and triple-negative breast carcinomas (TNBC), and Ki 67 index grades based on St Gallen criteria, intratumoral and peritumoral TB and PDC grades as per the International Tumor Budding Consensus Conference (ITBCC) criteria for colon and correlation between these and other histological features with the molecular subtypes were done. Statistical Analysis: Chi-square test, univariate and multivariate logistic regression models were used. Results: Significant correlation was seen between TB and lymphovascular emboli, Luminal B tumors with high-grade TB and PDCs, Her 2 neu positive and TNBC tumors with low-grade TB, circumscribed tumor margins, tumor necrosis, and Luminal B, Her 2 neu positive and TNBC tumors with larger tumor size and high nuclear grades. Conclusions: TB and PDCs are useful in the prognostication of Luminal A and B tumors when the Ki 67 index values are low/intermediate. Her 2 neu positive and TNBC tumors have a high nuclear grade with necrosis and no association with TB or PDCs.

Federated Learning-Based Detection of Invasive Carcinoma of No Special Type with Histopathological Images.

Invasive carcinoma of no special type (IC-NST) is known to be one of the most prevalent kinds of breast cancer, hence the growing research interest in studying automated systems that can detect the presence of breast tumors and appropriately classify them into subtypes. Machine learning (ML) and, more specifically, deep learning (DL) techniques have been used to approach this problem. However, such techniques usually require massive amounts of data to obtain competitive results. This requirement makes their application in specific areas such as health problematic as privacy concerns regarding the release of patients' data publicly result in a limited number of publicly available datasets for the research community. This paper proposes an approach that leverages federated learning (FL) to securely train mathematical models over multiple clients with local IC-NST images partitioned from the breast histopathology image (BHI) dataset to obtain a global model. First, we used residual neural networks for automatic feature extraction. Then, we proposed a second network consisting of Gabor kernels to extract another set of features from the IC-NST dataset. After that, we performed a late fusion of the two sets of features and passed the output through a custom classifier. Experiments were conducted for the federated learning (FL) and centralized learning (CL) scenarios, and the results were compared. Competitive results were obtained, indicating the positive prospects of adopting FL for IC-NST detection. Additionally, fusing the Gabor features with the residual neural network features resulted in the best performance in terms of accuracy, F1 score, and area under the receiver operation curve (AUC-ROC). The models show good generalization by performing well on another domain dataset, the breast cancer histopathological (BreakHis) image dataset. Our method also outperformed other methods from the literature.

TRPS1, GATA3, and SOX10 expression in triple-negative breast carcinoma.

A diagnostic dilemma can be encountered when primary triple-negative breast carcinoma (TNBC) without an in situ component or metastatic TNBCs lose the currently used organ-specific marker such as GATA3, raising concerns about metastatic carcinoma from other sites. In the current study, we compared the newly identified breast marker TRPS1 with currently used breast markers GATA3 and SOX10 in whole-tissue sections from 315 cases of various subtypes of TNBC. TRPS1 was highly expressed in 100% of triple-negative primary and metastatic invasive lobular carcinomas, 99% of triple-negative primary and metastatic invasive breast carcinoma of no special type (IBC-NST), and 95% of metaplastic breast carcinomas. In contrast, GATA3 and SOX10 were expressed in 94% and 0% of invasive lobular carcinomas, 63% and 74% of IBC-NST, and 50% and 49% of metaplastic breast carcinomas, respectively. For special-type TNBCs, both TRPS1 and GATA3 were negative in acinic cell carcinomas, most cribriform adenoid cystic carcinomas, and neuroendocrine carcinomas, but positive in secretory carcinomas. Triple-negative apocrine carcinoma was the only subtype of TNBC with positive GATA3 but negative TRPS1. These data indicate that TRPS1 is a highly sensitive marker for TNBCs with positivity not only in GATA3/SOX10-positive TNBCs but also in almost all GATA3/SOX10-negative TNBCs.

Image processing improvements afford second-generation handheld optoacoustic imaging of breast cancer patients.

Background: Since the initial breast transillumination almost a century ago, breast cancer imaging using light has been considered in different implementations aiming to improve diagnostics, minimize the number of available biopsies, or monitor treatment. However, due to strong photon scattering, conventional optical imaging yields low resolution images, challenging quantification and interpretation. Optoacoustic imaging addresses the scattering limitation and yields high-resolution visualization of optical contrast, offering great potential value for breast cancer imaging. Nevertheless, the image quality of experimental systems remains limited due to a number of factors, including signal attenuation with depth and partial view angle and motion effects, particularly in multi-wavelength measurements. Methods: We developed data analytics methods to improve the accuracy of handheld optoacoustic breast cancer imaging, yielding second-generation optoacoustic imaging performance operating in tandem with ultrasonography. Results: We produced the most advanced images yet with handheld optoacoustic examinations of the human breast and breast cancer, in terms of resolution and contrast. Using these advances, we examined optoacoustic markers of malignancy, including vasculature abnormalities, hypoxia, and inflammation, on images obtained from breast cancer patients. Conclusions: We achieved a new level of quality for optoacoustic images from a handheld examination of the human breast, advancing the diagnostic and theranostic potential of the hybrid optoacoustic-ultrasound (OPUS) examination over routine ultrasonography.

[Correlations of Androgen Receptor Expression with Molecular Subtypes and Clinopathological Features of Invasive Breast Carcinoma of No Special Type in Tibet].

Objective To investigate the expression of androgen receptor(AR)and its correlations with different molecular subtypes and clinicopathological features of breast invasive carcinoma of no special type(IBC-NST)in females of Tibetan ethnic minority in Tibet.Methods This study enrolled 54 female patients of Tibetan ethnic minority with IBC-NST surgically removed in the Tibet Autonomous Region People's Hospital from December 2015 to March 2021 for retrospective analysis.The clinical and pathological data of all the enrolled patients were collected.The immunohistochemical method was employed to determine the expression of AR,cell proliferation marker antigen (Ki-67),estrogen receptor(ER),human epidermal growth factor receptor 2(HER-2),and progesterone receptor(PR).For those with unclear HER-2 results,fluorescence in situ hybridization was employed for the determination.The relationship of AR expression with molecular subtypes and clinicopathological features was then analyzed.Results The expression of AR in Tibetan female patients with IBC-NST was correlated with ER(χ2=8.200,P=0.004),PR(χ2=9.900,P=0.003),and molecular subtype(χ2=11.690,P=0.009)and not correlated with tumor location,age,size,histological grade,lymph node metastasis,vascular invasion,clinical stage,or expression of HER-2 and Ki-67(all P>0.05).Molecular subtype was correlated with histological grade(χ2=24.970, P=0.001),clinical stage(χ2=9.035, P=0.029),and lymph node metastasis(χ2=9.691,P=0.021).Conclusions The positive expression rate of AR in the triple-negative IBC-NST patients of Tibetan ethnic minority was significantly lower than that in ER-or PR-positive patients in Tibet.Molecular subtype was correlated with histological grade,clinical stage,and lymph node metastasis.

Syntaxin-1 and Insulinoma-Associated Protein 1 Expression in Breast Neoplasms with Neuroendocrine Features.

Introduction: A subset of breast neoplasia is characterized by features of neuroendocrine differentiation. Positivity for Neuroendocrine markers by immunohistochemistry is required for the diagnosis. Sensitivity and specificity of currently used markers are limited; based on the definitions of WHO Classification of Tumours, 5th edition, about 50% of breast tumors with features of neuroendocrine differentiation express chromogranin-A and 16% express synaptophysin. We assessed the applicability of two novel markers, syntaxin-1 and insulinoma-associated protein 1 (INSM1) in breast carcinomas. Methods: Hypercellular (Type B) mucinous carcinomas, solid papillary carcinomas, invasive carcinomas of no special type with neuroendocrine features and ductal carcinomas in situ of neuroendocrine subtype were included in our study. The immunohistochemical panel included chromogranin A, synaptophysin, CD56, syntaxin-1 and INSM1. The specificity of syntaxin-1 and INSM1 was determined using samples negative for chromogranin A, synaptophysin and CD56. Results: The sensitivity of syntaxin-1 was 84.7% (50/59), with diffuse positivity in more than 60% of the cases. Syntaxin-1 also had an excellent specificity (98.1%). Depending on the definition for positivity, the sensitivity of INSM1 was 89.8% (53/59) or 86.4% (51/59), its specificity being 57.4% or 88.9%. The sensitivities of chromogranin A, synaptophysin and CD56 were 98.3, 74.6 and 22.4%, respectively. Discussion: Syntaxin-1 and INSM1 are sensitive and specific markers of breast tumors with neuroendocrine features, outperforming chromogranin A and CD56. We recommend syntaxin-1 and INSM1 to be included in the routine neuroendocrine immunohistochemical panel.