Solid papillary carcinoma of the breast (SPC) is a rare tumor of the breast with the unique histology and frequent neuroendocrine differentiation. However, a real nature and diagnostic importance of the neuroendocrine differentiation have not been properly handled. And relationship between SPC and the other types of invasive breast carcinoma, especially neuroendocrine tumor of the breast (NETb), has not been fully explained. We conducted a clinicopathological study of SPC to tackle these problems.In the study, we included 127 cases of SPC with long-term follow-ups of up to 30 years. The incidence in the breast carcinoma was 2.0%. The patients with SPC had a significantly better prognosis and no patients died of the tumor. The 35 cases had only SPC in situ (SPC-IS), while the 92 cases had both SPC-IS and SPC with invasion (SPC-INV). Immunohistochemically, 123 of the 127 cases exhibited diffuse expression of one or more neuroendocrine markers. Fifty of the 92 cases had exclusively invasive SPC (iSPC) as the invasive component. Twenty-two cases of iSPC were combined with NETb and the 18 cases with MUC. Six of 8 cases with metastatic SPC-INV disclosed iSPC in the axillary lymph node.This study suggests that SPC is immunohistochemically compatible with NET of the systemic organs (NETs). And the unique morphology of SPC may represent a traditional histology of NETs. The study also indicates that SPC has close relationship between NETb and type B MUC. And SPC and NETb may represent a spectrum of the same disease.
Adenocarcinoma, Papillary , Breast Neoplasms , Carcinoma, Papillary , Neuroendocrine Tumors , Humans , Female , Follow-Up Studies , Carcinoma, Papillary/pathology , Breast/pathology , Breast Neoplasms/pathology , Neuroendocrine Tumors/pathology , Receptor Protein-Tyrosine Kinases , Biomarkers, Tumor
BACKGROUND: DNA adducts, covalent modifications to DNA due to exposure to specific carcinogens, cause the mispairing of DNA bases, which ultimately results in DNA mutations. DNA methylation in the promoter region, another type of DNA base modification, alters the DNA transcription process, and has been implicated in carcinogenesis in humans due to the down-regulation of tumor suppressor genes. Difficulties are associated with demonstrating the existence of DNA adducts or chemically modified bases in the human urological system. Apart from aristolochic acid-DNA adducts, which cause urothelial carcinoma and endemic nephropathy in a particular geographical area (Balkan), limited information is currently available on DNA adduct profiles in renal cell carcinoma and upper urinary tract urothelial carcinoma, including renal pelvic cancer and ureteral cancer. METHOD: To elucidate the significance of DNA adducts in carcinogenesis in the urothelial system, we investigated 53 DNA adducts in the non-tumoral renal parenchyma and non-tumoral renal pelvis of patients with renal cell carcinoma, upper urinary tract urothelial carcinoma, and other diseases using liquid chromatography coupled with tandem mass spectrometry. A comparative analysis of tissue types, the status of malignancy, and clinical characteristics, including lifestyle factors, was performed. RESULTS: C5-Methyl-2'-deoxycytidine, C5-hydroxymethyl-2'-deoxycytidine (5hmdC), C5-formyl-2'-deoxycytidine, 2'-deoxyinosine, C8-oxo-2'-deoxyadenosine, and C8-oxo-2'-deoxyguanosine (8-OHdG) were detected in the renal parenchyma and renal pelvis. 8-OHdG was more frequently detected in the renal pelvis than in the renal cortex and medulla (p = 0.048 and p = 0.038, respectively). 5hmdC levels were significantly lower in the renal pelvis of urothelial carcinoma patients (n = 10) than in the urothelium of patients without urothelial carcinoma (n = 15) (p = 0.010). Regarding 5hmdC levels in the renal cortex and medulla, Spearman's rank correlation test revealed a negative correlation between age and 5hmdC levels (r = - 0.46, p = 0.018 and r = - 0.45, p = 0.042, respectively). CONCLUSIONS: The present results revealed a reduction of 5hmdC levels in the non-tumoral urinary tract mucosa of patients with upper urinary tract urothelial carcinoma. Therefore, the urothelial cell epithelia of patients with upper urinary tract cancer, even in non-cancerous areas, may be predisposed to urothelial cancer.
BACKGROUND: Field cancerization is a popular concept regarding where cancer cells arise in a plane, such as the opened-up gastrointestinal mucosa. The geospatial distribution of DNA adducts, some of which are believed to initiate mutation, may be a clue to understanding the landscape of the preferred occurrence of gastric cancer in the human stomach, such that the occurrence is much more frequent in the lesser curvature than in the greater curvature. METHODS: Seven DNA adducts, C5-methyl-2'-deoxycytidine, 2'-deoxyinosine, C5-hydroxymethyl-2'-deoxycytidine, N6-methyl-2'-deoxyadenosine, 1,N6-etheno-2'-deoxyadenosine, N6-hydroxymethyl-2'-deoxyadenosine, and C8-oxo-2'-deoxyguanosine, from different points and zones of the human stomach were semi quantitatively measured by liquid chromatography/tandem mass spectrometry. The differences in the quantity of these DNA adducts from the lesser and greater curvature, the upper, middle and lower third zones, the anterior and posterior wall of the stomach, and the mucosae distant from and near the tumor were compared to determine whether the location preference of cancer in the stomach could be explained by the distribution of these DNA adducts. Comparisons were conducted considering the tumor locations and operation methods. CONCLUSIONS: Regarding the DNA adducts investigated, significant differences in quantities and locations in the whole stomach were not noted; thus, these DNA adducts do not explain the preferential occurrence of cancer in particular locations of the human stomach.
BACKGROUND: A comprehensive understanding of DNA adducts, one of the most plausible origins of cancer mutations, is still elusive, especially in human tissues in clinical settings. Recent technological developments have facilitated the identification of multiple DNA adducts in a single experiment. Only a few attempts toward this "DNA adductome approach" in human tissues have been reported. Geospatial information on DNA adducts in human organs has been scarce. AIM: Mass spectrometry of human gastric mucosal DNA was performed to identify DNA adducts associated with environmental factors. MATERIALS AND METHODS: From 59 subjects who had received gastrectomy for gastric cancer, 306 samples of nontumor tissues and 15 samples of tumors (14 cases) were taken for DNA adductome analysis. Gastric nontumor tissue from autopsies of 7 subjects without gastric cancer (urothelial cancer, hepatocellular carcinoma, lung cancer each; the other four cases were without any cancers) was also investigated. Briefly, DNA was extracted from each sample with antioxidants, digested into nucleosides, separated by liquid chromatography, and then electrospray-ionized. Specific DNA adducts were identified by mass/charge number and column retention time compared to standards. Information on lifestyle factors such as tobacco smoking and alcohol drinking was taken from the clinical records of each subject. RESULTS: Seven DNA adducts, including modified bases, C5-methyl-2'-deoxycytidine, 2'-deoxyinosine, C5-hydroxymethyl-2'-deoxycytidine, N6-methyl-2'-deoxyadenosine, 1,N6-etheno-2'-deoxyadenosine, N6-hydroxymethyl-2'-deoxyadenosine, and C8-oxo-2'-deoxyguanosine, were identified in the human stomach and characterized. Intraindividual differences according to the multiple sites of these adducts were noted but were less substantial than interindividual differences. N6-hydroxymethyl-2'-deoxyadenosine was identified in the human stomach for the first time. The amount of C5-hydroxymethyl-2'-deoxycytidine was higher in the stomachs of subjects without gastric cancer than in the nontumor and tumor portions of the stomach in gastric cancer patients. Higher levels of 1,N6-etheno-2'-deoxyadenosine were detected in the subjects who reported both smoking and drinking than in those without these habits. These DNA adducts showed considerable correlations with each other. CONCLUSIONS: We characterized 7 DNA adducts in the nontumor portion of the human stomach in both gastric cancer subjects and nongastric cancer subjects. A reduction in C5-hydroxymethyl-dC even in the nontumor mucosa of patients with gastric cancer was observed. Smoking and drinking habits significantly influenced the quantity of one of the lipid peroxidation-derived adducts, etheno-dA. A more expansive DNA adductome profile would provide a comprehensive understanding of the origin of human cancer in the future.
