Clinicopathologic Analysis Of Breast Tumors With Papillary Structure

Background and purposeBreast cancer is one of the leading causes of cancer death in women and is the most prevalent malignant tumor in women globally.The major focus of research on breast cancer has shifted to ways to prevent overtreatment and undertreatment of cancer because it is a diverse illness.A category of epithelial tumors with a vascular fiber axis known as breast cancer with papillary structure includes benign,low-grade,and malignant tumors.It includes Intraductal papilloma(IDP),Papillary ductal carcinoma in situ(IDPC),Encapsulated papillary carcinoma(EPC),Encapsulated papillary carcinoma with invasion,Solid papillary carcinoma(SPC),Solid papillary carcinoma with invasion,Invasive papillary carcinoma(IPC),and Tall cell carcinoma with reversed polarity(TCCRP).Clinical signs,pathological modifications,molecular phenotypes,treatment strategies,and prognosis are all highly variable.Currently,the majority of domestic research on breast tumors with a papillary form are of a single kind,and the debate is mostly directed toward the analysis of the clinicopathological characteristics and the imaging diagnosis of a single type.In order to give a reference for the clinicopathological differential diagnosis of related breast cancers,the primary goal of this study is to undertake an extensive examination and analysis of a range of breast tumors with papillary shape.Method1.Retrospective analysis was performed on 305 female patients with papillary breast cancer who met the enrollment requirements and had surgical treatment in the Department of Breast Surgery at Qilu Hospital of Shandong University between January 2015 and May 2021.Age,tumor size,metastasis to the axillary lymph nodes,expression of the ER,PR,HER2 receptor,and Ki67 were all gathered and examined.By conducting a search of the Qilu Hospital of Shandong University medical record management system(United system),in addition to telephone follow-up,the survival of patients,including survival and tumor recurrence and metastasis,is determined.Breast cancers with papillary structure were investigated for their prognosis and their affecting variables were examined.2.To study the immunophenotype of breast tumors with papillary structure by immunohistochemistry.To investigate the expression of Insulinoma-associated protein 1(INSM1)in SPC and compare it with Synaptophysin(Syn)and Chromogranin A(CgA).Analyze the feasibility of INSM1 as a marker of breast neuroendocrine.3.The TCGA database(portal.gdc.cancer-gov)and the GTEx database were used to download transcriptome sequencing data and patient clinical data for breast cancer tissue and normal breast tissue.The LIMMA program in R was used to find the differently expressed genes,and "ggplot2" in R was used to create a volcanic map to visualize the differently expressed gene identification.The "clusterProfiler" software in R was used to conduct functional enrichment analysis of differential genes.The STRING website was used to build the protein-protein interaction(PPI)network of the differential genes.Cytoscape version 3.9.1 was used to view it,and molecular Complex Assay was used to do further analysis(MCODE).Using Cytoscape to identify the hub genes and the DGIdb database to build the gene-drug interactions.4.Targeted NGS molecular genetic analysis was performed in 3 cases diagnosed with high-cell carcinoma with reversed polarity.Result1.In total,we collected a sample of 305 cases,in the 4 types of malignant tumors,the average age of various types of tumors exists a marked difference between the groups,mainly in the mean age of tubular breast cancer and the other 3 groups of tumors have some statistical differences,while the other groups of 3 tumors have no statistical difference in average age.There were no differences in tumor size between groups.There are significant statistical differences in tumor transmission,TNM phase,ER,PR,HER-2,and Ki-67 expression.The patient’s overall prognosis was better,with 2 patients with higher levels of nuclei and concomitant lymph nodal transfusions.2.Of the 41 patients with real breast cancer in this study,28 were Syn-positive(68.3%),22 were CgA-positive(53.7%)and 33 were INSM1-positive(80.5%);of the 26 patients with non-real breast cancer,9 were Syn positive(34.7%),2 were CgA positive(7.7%),and 10 had INSM1 positive(38.5%).The sensitivity and specificity of Syn were 68.3%and 65.4%respectively;The sensitivity and specificity of CgA were 53.7%and 92.3%respectively,and The sensitivity and specificity of INSM1 were 80,5%and 61.5%respectively.The sensitivity of INSM1 is higher than Syn and CgA,and the specificity is similar to Syn but lower than CgA.3.Through the data screening,a total of eight tumor samples and 459 normal samples were screened to identify 6153 differential genes,including 1803 upgraded genes and 4350 downgraded genes.The upgraded differential genes mainly exhibit obvious disorders of gene expression in three ways,namely,interleaf transition,cell cycle,and thread division.The downward differential genes mainly exhibit obvious gene expression disorders in three ways,namely,upper inter leukemic conversion,muscle contraction system,and G-protein coupled receptor and receptor combination.A total of six nodal genes were screened,which were associated with the onset and development of breast tumors with Papillary structure.Compared to normal breast tissue,these six nodes are more expressed in tumor tissue.4.Targeted NGS molecular genetic analysis of 3 patients diagnosed with TCCRP showed that 3 TCCRP patients were complicated by IDH2 hot spot mutations(p.R172S)and 2 with PIK3CA hot spot mutations(p.H1047R).In addition,one ABCB1 hot spot mutation(p.K536R)and one PIK3R1 non-frameshift deletion mutation(p.N294_T306del)were detected in tumor tissue.Conclusion1.The prognosis of breast tumors with papillary structure is good,but there is still a risk of distant metastasis in patients with lymph node metastasis or advanced nuclear grade,so it is necessary to adhere to long-term follow-up of these patients.2.INSM1 can be used with Syn and CgA as auxiliary diagnostic detection means for SPC.3.Six genes(CDK1,CCNA2,CDC20,CCNB1,BUB1,and TOP2A)were associated with the occurrence and progression of breast tumors with papillary structure.Whether these genes can be used as potential prognostic biomarkers and therapeutic targets remains to be verified by further clinical studies.4.IDH2 R172 hot spot mutation and PIK3CA hot spot mutation were found in high-cell carcinoma with polarity reversal.The study also identified new types of molecular mutations that may be potential therapeutic targets for high-cell carcinoma with polarity reversal,which still needs to be confirmed in further experiments.