Aggressive Histologic Subtype Research Articles

Neoadjuvant Cisplatin, Gemcitabine, and Docetaxel in Sarcomatoid Bladder Cancer: Clinical Activity and Whole Transcriptome Analysis.

Sarcomatoid urothelial cancer of the bladder (SBC) is a rare, but aggressive histological subtype for which novel treatments are needed. We evaluated the clinical activity and safety of neoadjuvant cisplatin plus gemcitabine plus docetaxel (CGD) in muscle-invasive patients with SBC and assessed SBC tumor biology by whole transcriptome RNA sequencing. A single-institution, retrospective analysis of muscle-invasive SBC patients treated with neoadjuvant CGD with molecular analysis. Patients received cisplatin 35 mg/m2 + gemcitabine 800 mg/m2 + docetaxel 35 mg/m2 intravenously on days 1 and 8 + pegfilgrastim 6 mg subcutaneously on day 9 every 3 weeks for 4 cycles followed by cystectomy. The primary endpoint was pathologic complete response (ypCR) rate. Sixteen patients with SBC received neoadjuvant CGD with a ypCR rate of 38% and a < ypT2 rate of 50%. Grade 3 and 4 toxicity occurred in 80% and 40% of patients, but was manageable with 81% of patients completing > 3 CGD cycles. Whole transcriptome RNA sequencing demonstrates co-clustering of SBC with conventional urothelial tumors. SBC tumors are characterized by basal-squamous and stroma rich gene signatures with frequent increased expression of immune checkpoint (CD274 (PD-L1)), chemokine (CXCL9), and T-cell (CD8A) genes. SBC is a chemosensitive subtype, with ypCR rate similar to urothelial bladder cancer following CGD neoadjuvant therapy. Whole transcriptome tissue analyses demonstrate increased expression of immune checkpoint and T-cell genes with therapeutic implications.

Exploring U.S. Hispanic origin groups diagnosed with uterine cancer - Are there disparities?

ObjectiveTo evaluate patterns and trends of uterine cancer among Hispanic subgroups. MethodsThe United States Cancer Statistics (USCS), National Cancer Database (NCDB), and World Population Review were used to obtain data on incidence, demographic characteristics, and cancer histology. Joinpoint regression program was used for statistical analysis. ResultsBased on 2001–2017 USCS data, the overall incidence of uterine cancer was 27.46 vs. 23.29/100,000 in Hispanics vs. non-Hispanic Whites. There was an over 2-fold higher annual increase in the incidence in Hispanics (1.94%; p < 0.001) vs. Whites (0.85%; p < 0.001), particularly in local stage disease. There was an increase in grade 1 endometrioid carcinoma (1.48%; p < 0.001 vs. −0.52%; p = 0.1) and aggressive histologic subtypes (4.04% p = 0.000 vs. 2.53% p = 0.000) in Hispanics vs. Whites.Using the NCDB (2004–2015), we analyzed 17,351 Hispanics by subgroup (Mexican, South/Central American, Puerto Rican, Cuban, and Dominican). Over the 12 years, there was an increase in the proportion of uterine cancer diagnoses in all Hispanics (5.2% to 11.0%; p < 0.0001). Dominican patients experienced the largest increase in diagnosis (2.6% to 14.9%; p < 0.0001), the highest proportion of advanced disease at 28.0% (p < 0.0001), and the highest incidence of non-endometrioid histologies at 37.1% (p < 0.0001).World Population Review 2023 revealed the highest female obesity rates in Puerto Rico (51.4%), the Dominican Republic (34.1%), and Mexico (32.8%). ConclusionUterine cancer incidence is increased in Hispanics, with the largest increase in Dominican women with more advanced stages and high-risk histologic subtypes. The impact of obesity on cancer risk, especially in Puerto Ricans, Dominicans, and Mexicans, warrants further investigation.

Adenosquamous carcinoma of prostate: An entity out of the ordinary

Adenosquamous carcinoma (ASC) of the prostate is an extremely rare, aggressive histological subtype of prostate cancer. We report one such case here of a 73-year-old man with prostatic malignancy with a combination of squamous and glandular components. Immunohistochemistry with p40, AMACR and HMWCK corroborated the diagnosis of ASC. The squamous component being refractory, is better amenable to aggressive surgery, highlighting the importance of recognising this entity. Bony metastasis was not seen in this patient. Serum PSA was near normal.

Comprehensive analysis of orbital lymphoma in a Turkish cohort: clinical characteristics, histological subtypes, treatment modalities, prognostic factors, and implications for management.

The study analysed the clinical characteristics, treatment approaches, and survival outcomes of 97 consecutive patients with orbital lymphoma (OL) over a 25-year period at. The median age of the patients was 57.6years, and 59.8% (n = 58) were male. Marginal zone lymphoma constitutes the most prevalent subtype, accounting for 67% of cases, whereas other common subtypes include diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma, and T-cell lymphomas. Unilateral involvement was observed in the majority of cases (72.3%). Common clinical presentations included mass (30.9%), swelling (26.8%), and epiphora (11.3%). Of the patients, 7.2% received rituximab alone, 14.4% received radiotherapy alone, 48.5% received chemotherapy, 27.8% received radiotherapy plus rituximab, 22.7% received radiotherapy plus chemotherapy, and 5.2% underwent surgery as the first-line treatment. During a median follow-up of 4.3years, 15.5% of patients experienced relapse or disease progression. The 5-year and 10-year progression-free survival rates were 84.1% and 79.1%, respectively. This study contributes to our understanding of OLs and provides a foundation for further investigations in this field. Male gender, presence of B symptoms, advanced stage, secondary orbital lymphoma, aggressive histological subtype, and elevated serum lactate dehydrogenase levels were associated with poorer (either inferior or worse) progression-free survival.

Malignant Transformation of Long-Standing Ileal Crohn's Disease Likely Favors Signet Ring Cell Adenocarcinoma Histology.

Signet ring cell adenocarcinomas (SRCCs) are a rare and aggressive histological subtype of adenocarcinomas typically with poor prognosis usually secondary to late stage at detection. In the small bowel, they constitute only 1% of all malignancies. In the last decade, there have been multiple case reports and small case series that have identified SRCCs, typically in the ileum, in patients with Crohn's disease. Crohn's disease is a transmural inflammatory condition that normally manifests in the distal ileum and colon, and is known to temporally increase the risk of malignancy. Given the profound rarity of SRCCs, establishing an association between Crohn's disease and SRCC is challenging. In this study, we performed a systematic review of case reports and small case series describing small bowel SRCCs in Crohn's disease patients. Most cases were found in the distal/terminal ileum, at a mean age of 59 years old. Virtually all tumors were locally advanced (pathological T stage 3 and 4), typically with at least N1 nodal disease. Two case studies (one is a case-control study and the other a cohort design) demonstrated that small bowel SRCC, as opposed to conventional adenocarcinoma, was significantly correlated to a history of Crohn's disease (35% vs. 0%, 73.5% vs. 28.5%), with a propensity to arise in the ileum (95% vs. 30%, 66.7% vs. 42.1%), and at earlier mean age (43 vs. 68 years, 53.7 vs. 61.7 years). We additionally used the Surveillance, Epidemiology, and End Results (SEER) database for insights into the clinicoepidemiological characteristics of ileum SRCCs. SRCCs composed 28.1% of all ileal SRCCs, compared to 11.0% for the adenocarcinomas, with a younger age at diagnosis (60.7 vs. 64.6 years), more distant disease at presentation (41.3% vs. 26.4%), and shorter overall median survival time (20 vs. 39 months). In summary, while there is limited direct evidence to support an association between small bowel SRCC and Crohn's disease, the phenomenon has been increasingly documented in the literature in the last decade. Clinicians treating Crohn's disease patients should consider this in their differential diagnosis, particularly when managing disease complications, as early detection and surgical intervention offer the best prognosis.

Patient-derived organoids identify tailored therapeutic options and determinants of plasticity in sarcomatoid urothelial bladder cancer

Sarcomatoid Urothelial Bladder Cancer (SARC) is a rare and aggressive histological subtype of bladder cancer for which therapeutic options are limited and experimental models are lacking. Here, we report the establishment of a long-term 3D organoid-like model derived from a SARC patient (SarBC-01). SarBC-01 emulates aggressive morphological, phenotypical, and transcriptional features of SARC and harbors somatic mutations in genes frequently altered in sarcomatoid tumors such as TP53 (p53) and RB1 (pRB). High-throughput drug screening, using a library comprising 1567 compounds in SarBC-01 and conventional urothelial carcinoma (UroCa) organoids, identified drug candidates active against SARC cells exclusively, or UroCa cells exclusively, or both. Among those, standard-of-care chemotherapeutic drugs inhibited both SARC and UroCa cells, while a subset of targeted drugs was specifically effective in SARC cells, including agents targeting the Glucocorticoid Receptor (GR) pathway. In two independent patient cohorts and in organoid models, GR and its encoding gene NR3C1 were found to be significantly more expressed in SARC as compared to UroCa, suggesting that high GR expression is a hallmark of SARC tumors. Further, glucocorticoid treatment impaired the mesenchymal morphology, abrogated the invasive ability of SARC cells, and led to transcriptomic changes associated with reversion of epithelial-to-mesenchymal transition, at single-cell level. Altogether, our study highlights the power of organoids for precision oncology and for providing key insights into factors driving rare tumor entities.

Exploring the cell-free total RNA transcriptome in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma patients as biomarker source in blood plasma liquid biopsies.

Diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) are aggressive histological subtypes of non-Hodgkin's lymphoma. Improved understanding of the underlying molecular pathogenesis has led to new classification and risk stratification tools, including the development of cell-free biomarkers through liquid biopsies. The goal of this study was to investigate cell-free RNA (cfRNA) biomarkers in DLBCL and PMBCL patients. Blood plasma samples (n=168) and matched diagnostic formalin-fixed paraffin-embedded (FFPE) tissue samples (n=69) of DLBCL patients, PMBCL patients and healthy controls were collected between 2016-2021. Plasma samples were collected at diagnosis, at interim evaluation, after treatment, and in case of refractory or relapsed disease. RNA was extracted from 200 µl plasma using the miRNeasy serum/plasma kit and from FFPE tissue using the miRNeasy FFPE kit. RNA was subsequently sequenced on a NovaSeq 6000 instrument using the SMARTer Stranded Total RNA-seq pico v3 library preparation kit. Higher cfRNA concentrations were demonstrated in lymphoma patients compared to healthy controls. A large number of differentially abundant genes were identified between the cell-free transcriptomes of DLBCL patients, PMBCL patients, and healthy controls. Overlap analyses with matched FFPE samples showed that blood plasma has a unique transcriptomic profile that significantly differs from that of the tumor tissue. As a good concordance between tissue-derived gene expression and the immunohistochemistry Hans algorithm for cell-of-origin (COO) classification was demonstrated in the FFPE samples, but not in the plasma samples, a 64-gene cfRNA classifier was developed that can accurately determine COO in plasma. High plasma levels of a 9-gene signature (BECN1, PRKCB, COPA, TSC22D3, MAP2K3, UQCRHL, PTMAP4, EHD1, NAP1L1 pseudogene) and a 5-gene signature (FTH1P7, PTMAP4, ATF4, FTH1P8, ARMC7) were significantly associated with inferior progression-free and overall survival in DLBCL patients, respectively, independent of the NCCN-IPI score. Total RNA sequencing of blood plasma samples allows the analysis of the cell-free transcriptome in DLBCL and PMBCL patients and demonstrates its unexplored potential in identifying diagnostic, cell-of-origin, and prognostic cfRNA biomarkers.

THU489 The Role Of Noncoding Genes With The Bidirectional Promoter In Triple-negative Breast Cancer

Abstract Disclosure: B. Yang: None. M. Sedano: None. M.V. Jimenez: None. E.I. Ramos: None. S. Gadad: None. Breast cancer is the second leading cause of cancer mortality in women after lung cancer. Breast cancer is grouped into different molecular subtypes; triple-negative breast cancer (TNBC) accounts for 20%. TNBC is a highly aggressive histologic subtype; the lack of unique therapeutic targets makes it harder to treat. Recent studies have implicated genes involved in cancers that are transcribed using a process known as divergent transcription. The expression of these genes is tightly regulated; however, many escape regulation and become aberrantly expressed in tumors. Interestingly, our genomic analysis suggests that several of these genes encode noncoding transcripts. Analysis of transcriptome from different tissue types, including cancer and normal, revealed that many are upregulated in various cancers. Selected divergent transcript, such as lncRNA67, has been completely characterized (transcription start and stop site, 5’ cap, polyA tail, and exon/intron structure) and cloned. In functional assays, overexpression of lncRNA67 regulates gene expression, cell proliferation, and tumor growth. Our molecular analyses indicate that lncRNA67 plays a vital role in triple-negative breast cancer biology. Collectively, our results suggest that divergent transcripts are an integral component of cancer biology and present a new repertoire of diagnostic and potential therapeutic targets. Presentation: Thursday, June 15, 2023

The ErbB Signaling Network and Its Potential Role in Endometrial Cancer.

Endometrial cancer (EC) is the second most common malignancy of the female reproductive system worldwide. The updated EC classification emphasizes the significant role of various signaling pathways such as PIK3CA-PIK3R1-PTEN and RTK/RAS/β-catenin in EC pathogenesis. Some of these pathways are part of the EGF system signaling network, which becomes hyperactivated by various mechanisms and participates in cancer pathogenesis. In EC, the expression of ErbB receptors is significantly different, compared with the premenopausal and postmenopausal endometrium, mainly because of the increased transcriptional activity of ErbB encoding genes in EC cells. Moreover, there are some differences in ErbB-2 receptor profile among EC subgroups that could be explained by the alterations in pathophysiology and clinical behavior of various EC histologic subtypes. The fact that ErbB-2 receptor expression is more common in aggressive EC histologic subtypes (papillary serous and clear cell) could indicate a future role of ErbB-targeted therapies in well-defined EC subgroups with overexpression of ErbB receptors.

Spatial transcriptomics delineates molecular features and cellular plasticity in lung adenocarcinoma progression

Indolent (lepidic) and aggressive (micropapillary, solid, and poorly differentiated acinar) histologic subtypes often coexist within a tumor tissue of lung adenocarcinoma (LUAD), but the molecular features associated with different subtypes and their transitions remain elusive. Here, we combine spatial transcriptomics and multiplex immunohistochemistry to elucidate molecular characteristics and cellular plasticity of distinct histologic subtypes of LUAD. We delineate transcriptional reprogramming and dynamic cell signaling that determine subtype progression, especially hypoxia-induced regulatory network. Different histologic subtypes exhibit heterogeneity in dedifferentiation states. Additionally, our results show that macrophages are the most abundant cell type in LUAD, and identify different tumor-associated macrophage subpopulations that are unique to each histologic subtype, which might contribute to an immunosuppressive microenvironment. Our results provide a systematic landscape of molecular profiles that drive LUAD subtype progression, and demonstrate potentially novel therapeutic strategies and targets for invasive lung adenocarcinoma.

Epidemiological survival predictors of cancer of the corpus uteri: a population-based analysis

Cancer of the corpus uteri (CCU) is one of the most common gynecological malignancies in high- and middleincome countries. The objective of the study was to evaluate the factors predicting survival in CCU patients over the period 2000-2021 using the data of population-based cancer registry of the Arkhangelsk region. Material and Methods. Cancer-specific survival (CSS) of patients with CCU for the period 2000-21 was evaluated using life tables and Kaplan-Mayer methods with a log-rank test. The Cox proportional hazards regression model was used to assess the effect of prognostic factors on survival time. Results. A total of 3272 cases were selected for the analysis. The 5-year survival rates improved from 70.6 % in 2000-04 to 75.6 % in 2015-19. In stage I, II, III, and IV CUN, the 5-year survival rates were 90.8 % (95 % CI 89.3-92.0 %), 71.1 (95 % CI 66.3-75.4 %), 46.7 (95 % CI 41.4-51.8 %), and 3.9 (95 % CI 1.5-7.5 %), respectively; p&lt;0.001. In the multivariate regression model, for stage II, III, and IV CCU, the hazard ratios for death from cancer were respectively 2.69 (2.14-3.39), 5.73 (4.66-7.03), and 20.26 (16.13-25.44) compared to stage I. The risk of death from CCU was 2.0-2.7 times higher in patients with aggressive histological subtypes and sarcomas compared to that in patients with endometrioid adenocarcinoma; 2.0-2.8 times higher in patients older than 60 years compared to younger patients, and 1.3 times higher in rural patients compared to urban patients (p&lt;0.05). There was no increase in the risk of death from CCU over the period of COVID-19 pandemic. Conclusion. In this population-based study, we have found that the survival of patients with CCU is significantly affected by age and place of residence, which may indicate a limited access of some patients to effective treatment and requires further analysis. No increased risk of death from CCU during the COVID-19 pandemic was found.

Modifiable risk factors for glioblastoma: a systematic review and meta-analysis.

Glioblastoma (GBM) is the most common and aggressive glioma histological subtype, associated with high disability and poor survival. The etiology of this condition is still mostly unknown, and evidence about risk factors is elusive. The aim of this study is to identify modifiable risk factors for GBM. Electronic search was performed by two reviewers independently using the keywords and MeSH terms 'glioblastoma' OR 'glioma' OR 'brain tumor' AND 'risk factor'. The inclusion criteria were (1) observational studies or experimental studies on humans, (2) studies assessing the association between glioblastoma and exposure to modifiable conditions, and (3) studies published in English or Portuguese. Studies on the pediatric population or about exposure to ionizing radiation were excluded. A total of 12 studies were included. Seven were case-control studies, and five were cohort studies. The risk factors assessed included body mass index, alcohol consumption, exposure to magnetic fields, diabetes mellitus type 2 (DM2), and use of non-steroidal anti-inflammatory drugs (NSAID). No significant link was found between GBM incidence and DM2 or magnetic field exposure. On the other hand, higher BMI, alcohol consumption, and NSAID use demonstrated a protective effect on GMB risk. However, given the limited number of studies, it is not possible to obtain a behavioral recommendation; instead, these findings are relevant to guide future basic scientific studies on GBM oncogenesis.

Giant Cell Osteoclast-Like Bladder Carcinoma: A Case Report

Introduction: Osteoclast-like giant cell bladder carcinomas are an extremely unusual and aggressive histological subtype of urothelial carcinomas. Only 30 cases have been reported globally. Clinical case: A 79-year-old male patient was presented to our Urology Department due to macroscopic hematuria that persisted for six months. As part of his diagnostic protocol, a CT scan of the abdomen and pelvis with elimination phase was performed, finding a filling defect of 12 mm at the level of the posterior wall of the bladder. A cystoscopy was subsequently performed, confirming the presence of a 1.5 cm bladder tumor, which was resected in its entirety. Pathology analysis with hematoxylin and eosin stain revealed a composition of mononuclear cells and osteoclast-like giant cells. Immunohistochemistry was positive for epithelial markers cytokeratins AE1/AE3, EMA, P53, and CD68. Conclusion: Osteoclast-like giant cell bladder carcinomas are extremely unusual and aggressive. The only diagnostic method is through immunohistochemistry, confirming the presence of epithelial markers for urothelium in the neoplastic cells. Radical surgical treatment is recommended and there has been no proven effective adjuvant treatment to date. The patients’ median survival is 15 months.

The role of histological subtypes in the survival of patients diagnosed with cutaneous or mucosal melanoma in the United States of America.

Literature presents limited information on histological subtypes and their association with other factors influencing the survival of melanoma patients. To explore the risk of death due to melanoma associated with histological subtypes, this retrospective study used the Surveillance, Epidemiology, and End Results program (SEER) data from 1998 to 2019. A total of 27,532 patients consisting of 15,527 males and 12,005 females. The Hypertabastic Accelerated Failure Time model was used to analyze the impact of histology on the survival of patients with cutaneous or mucosal melanoma. The median survival time (MST) for cutaneous patients was 149 months, whereas those diagnosed with mucosal melanoma was 34 months. Nodular melanoma had a hazard ratio of 3.40 [95% CI: (2.94, 3.94)] compared to lentigo maligna melanoma. Across all histological subtypes, females had a longer MST, when compared to males. The hazard ratio (HR) of distant to localized melanoma was 9.56 [95% CI: (7.58, 12.07)]. Knowledge of patients' histological subtypes and their hazard assessment would enable clinicians and healthcare providers to perform personalized treatment, resulting in a lower risk of complication and higher survivability of melanoma patients. Significant factors were stage of the disease, age, histology, sex, and income. Focus should be placed on high-risk populations with severe and aggressive histological subtypes. Programs that emphasize preventive measures such as awareness, education, and early screening could reduce risk.

Association of the Duffy-null allele and endometrial cancer characteristics: An effort to explore racial disparity in Black women with endometrial cancer.

5603 Background: Efforts are needed to identify factors that account for the disparately high mortality in Black women with endometrial cancer. The Duffy antigen receptor for chemokines (DARC) is expressed on erythrocytes and endothelial cells and modulates levels of inflammatory chemokines in circulation and in tissues. The African ancestry-specific Duffy-null allele, in which erythrocyte expression and function of DARC is lost, is associated with worse breast cancer phenotypes and survival. Here, we characterize Duffy-null status and associated prognostic and clinical outcomes in patients with endometrial cancer. Methods: Patients with endometrial cancer were prospectively consented, and germline DNA was extracted from saliva or blood samples. Duffy-null genotype was determined using an allelic discrimination assay. Associations between Duffy-null genotype status and clinicopathologic characteristics were performed using Fisher’s Exact analysis. Results: 33 patients were enrolled (Table); 17 (51.5%) were Duffy-null, 5 (15.2%) were Duffy-null allele carriers, and 11 (33.3%) were non-carriers. Compared with non-carriers, Duffy-null patients were more likely to be Black (100% v 9.1%, p&lt;0.0001) and have non-endometrioid histology (64.7% v 10%, p=0.0173). There was a trend towards higher rates of grade 3 histology (70.6% v 36.6%), intact tumor mismatch repair (MMR) (86.7% v 54.6%), estrogen receptor (ER) negative tumor status (25% v 10%), advanced stage (37.5% v 18.2%), and positive lymph nodes (25% v 0%) (Table). Over a minimum of 12 months of follow up, only Duffy-null individuals died from disease (4 v 0, p=0.0006). Conclusions: Duffy-null status was associated Black race, aggressive histologic subtypes, intact MMR mechanisms, and worse survival. Further investigation is needed to explore the underlying mechanism of the Duffy-null phenotype on endometrial cancer outcomes to better elucidate risk factors and underlying causes that may contribute to endometrial cancer disparities.[Table: see text]

The changing landscape of small-cell lung cancer.

e20634 Background: Small-cell lung cancer (SCLC) is an aggressive histologic subtype of lung cancer with distinct biology and clinical course. The aim of this study is to investigate the trends in demographics and outcomes. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) database to assess the incidence, demographics, and survival for SCLC using SEER 8 (8 registries), which include data from 1975 to 2019. The pattern of metastases was evaluated using SEER 17 from 2010 to 2019. Jointpoint analysis was used to calculate the trends in annual percentage change according to year of diagnosis. Results: There were 530,198 patients with lung cancer, including 73,362 (13.8%) patients with SCLC in the SEER 8. The percentage of SCLC among all lung tumors progressively increased from 13.3% in 1975 to a peak of 17.5% in 1986, followed by steadily decrease since 1990, reaching 11.1% in 2019. The incidence per 100,000 population increased from 9.5 in 1975 to 15.3 in 1986 followed by a gradual decline to 6.5 in 2019. Among patients with SCLC included in SEER 8, demographic changes from 1975-1979 to 2015-2019 included increased median age at diagnosis from 63 years to 69 and increased percentage of women from 31.4% to 51.2%. The percentage of patients with stage IV increased from 56.9% to 63.8% from 1995-1999 to 2000-2004, and to 69.5% in 2010-2014 without further increase. Among the 55,035 patients with SCLC in SEER 17 from 2010 to 2019, the most common sites of metastasis at diagnosis were mediastinal lymph nodes (69.9%) liver (30.5%), bone (22.8%), and brain (15.8%). The median, 1-year, and 5-year overall survival increased from 6 months, 23%, and 3.6% respectively in 1975-1979 to 7 months, 30.8%, and 6.8% respectively in 2010-2019 (P &lt; 001). Conclusions: The incidence of SCLC in the United States reached a peak in 1985 to 1989 followed by a gradual decline. Demographic changes included an increased median age at diagnosis and the percentage of women, which surpassed men in the last study period. There was also an increase in the percentage of stage IV. The improvement in 5-year OS has been statistically significant but clinically modest.

Tumor immune microenvironment (TIME) analysis of stage I lung adenocarcinoma with micropapillary pattern.

e20510 Background: Micropapillary is one of the most aggressive histologic subtypes of lung adenocarcinoma, which is considered a poor prognostic marker. Comprehensive analysis of tumor immune microenvironment (TIME) features of micropapillary of early invasive lung adenocarcinoma may provide better insight and facilitate the development of novel strategies for early detection and intervention. Methods: A total of 15 patients who underwent anatomical resection and were pathologically diagnosed with stage I micropapillary adenocarcinomas were included in this study. Gene expression profiles (GEPs) of tumor immune-related 289 genes were analyzed using NanoString nCounter. Differentially expressed genes(DEGs), estimation of TIME cell infiltration, and TIME signatures between micropapillary and non-micropapillary were assessed. Results: The number of micropapillary and non-micropapillary patients was 5 and 10. The comparison revealed CD69, IL6, CXCL8, CXCL2, POLR2A and so on were significantly upregulated in the micropapillary group compared with the non-micropapillary group, while HLA-DPA1, IFIT2, and other seven genes were down-regulated in the micropapillary group. These DEGs were mostly enriched in “positive regulation of cytokine production”， “T cell activation”， “receptor ligand activity，” and “signaling receptor activator activity” pathways according to GO enrichment analysis. The results of the KEGG analysis revealed that genes were significantly enriched in “IL-17 signaling pathway”, “TNF signaling pathway”, “cytokine-cytokine receptor interaction”, and so on. Meanwhile, different immune infiltration of the two groups was analyzed. Totally, there was a better TIME cell infiltration in the micropapillary group compared with the non-micropapillary group. Especially, the score of DCs and mast cells was significantly higher in micropapillary group. However, TIME signature scores were similar in both groups. Conclusions: Our study demonstrated that the TIME between micropapillary and non-micropapillary of stage I lung adenocarcinoma was different. Increased mast cells explained poor prognosis in lung adenocarcinoma with micropapillary pattern. A high level of DCs infiltration indicated that micropapillary adenocarcinoma might benefit from immunotherapy.

Comparison of surgical resection of Axillary Lymph Nodes in Dogs with Mammary Gland Tumors with or without sentinel lymph node visualization with patent blue dye.

Dogs' axillary lymph node (ALN) is often difficult to locate before surgical resection. The anatomical location of ALN often discourages Veterinarians from surgical lymphadenectomy. Considering the limited literature available, the actual incidence of metastases and the prognostic relevance are poorly understood. A non-randomized, prospective clinical study was conducted with female dogs (n = 41) with mammary gland tumor (MGT) in the thoracic or cranial abdominal mammary glands. The study investigated the risks of ALN metastasis based on tumors clinical findings, tumor size, histopathological diagnosis and grade. The main aim of this study was to compare ALN resection with or without patent blue 2.5% (PB) dye injection for sentinel lymph node visualization. A total of 46 mastectomies were performed and five animals underwent two mastectomies. In the first group, 17 patients underwent a mastectomy and lymphadenectomy without PB injection (G1). In contrast, in the second group, 24 patients also received PB injections for sentinel lymph node mapping (G2). The ALN was identified in 38/46 cases (82%). The ALN was identified and excised in only 58% of surgeries in G1(19/46), while in group 2, the lymph node was identified in 92% of the cases and resected in 100% of the cases. The use of PB improves ALN's identification and reduces the surgical resection time in dogs with MGT. Surgical time differed between the two groups, as it was significantly shorter in the PB injection group compared to group 1 (80 vs. 45 min) (p < 0.0001). The overall frequency of ALN metastasis was 32%. Macroscopic abnormalities in the lymph nodes, tumor size (>3 cm), and diagnosis of anaplastic carcinoma or grade II/III mammary gland tumors were associated with a higher probability of ALN metastasis. Metastases in the ALNs are more common, in dogs presenting with tumors larger than 3 cm and diagnosed with aggressive histological subtypes. The ALNs should be removed for correct staging, prognostic evaluation, and decision for adjuvant therapy.

Metaplastic breast cancer: an all-round multidisciplinary consensus.

Metaplastic breast cancer (MpBC) is a rare and aggressive histologic subtype of breast cancer (BC) characterized by the presence of at least two cellular types, commonly epithelial and mesenchymal components. Despite growing evidence that MpBC is a unique entity, it has long been treated as a variant of nonspecial type (NST) BC. MpBC typically shows the phenotype of triple-negative breast cancer (TNBC), but compared to NST-TNBC, it is a relatively chemorefractory tumor associated with worse outcomes. Therefore, there is an urgent need to develop management guidelines specifically for MpBC to improve the prognosis of patients with early MpBC. This expert consensus aims to guide diagnosis and standardize clinical management of early MpBC among treating physicians. We provide guidance on the challenging radiological and pathological diagnosis of MpBC. Evidence on the involvement of genetic predisposition in the development of MpBC is also explored. We emphasize the importance of a multidisciplinary approach for the treatment of patients with early MpBC. The optimal surgery and radiotherapy approach is presented, as well as the opportunity offered by novel therapeutic approaches to increase treatment response in this chemoresistant subtype. Appropriate management of patients with MpBC is critical to reduce the high risk of local and distant recurrence that characterizes this disease.

542 Optically guided high-frequency ultrasound can distinguish basal cell carcinomas with aggressive histological subtypes

542 Optically guided high-frequency ultrasound can distinguish basal cell carcinomas with aggressive histological subtypes