scholarly journals Multi-gene signature of microcalcification and risk prediction among Taiwanese breast cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hsin-Tien Tsai ◽  
Ching-Shui Huang ◽  
Chao-Chiang Tu ◽  
Chih-Yi Liu ◽  
Chi-Jung Huang ◽  
...  

Abstract Microcalcification is one of the most common radiological and pathological features of breast ductal carcinoma in situ (DCIS), and to a lesser extent, invasive ductal carcinoma. We evaluated messenger RNA (mRNA) transcriptional profiles associated with ectopic mammary mineralization. A total of 109 breast cancers were assayed with oligonucleotide microarrays. The associations of mRNA abundance with microcalcifications and relevant clinical features were evaluated. Microcalcifications were present in 86 (79%) patients by pathological examination, and 81 (94%) were with coexistent DCIS, while only 13 (57%) of 23 patients without microcalcification, the invasive diseases were accompanied with DCIS (χ2-test, P < 0.001). There were 69 genes with differential mRNA abundance between breast cancers with and without microcalcifications, and 11 were associated with high-grade (comedo) type DCIS. Enriched Gene Ontology categories included glycosaminoglycan and aminoglycan metabolic processes and protein ubiquitination, indicating an active secretory process. The intersection (18 genes) of microcalcificaion-associated and DCIS-associated genes provided the best predictive accuracy of 82% with Bayesian compound covariate predictor. Ten genes were further selected for prognostic index score construction, and five-year relapse free survival was 91% for low-risk and 83% for high-risk group (log-rank test, P = 0.10). Our study suggested that microcalcification is not only the earliest detectable radiological sign for mammography screening but the phenomenon itself may reflect the underling events during mammary carcinogenesis. Future studies to evaluate the prognostic significance of microcalcifications are warranted.

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Atif Ali Hashmi ◽  
Kashif Ali Hashmi ◽  
Muhammad Irfan ◽  
Saadia Mehmood Khan ◽  
Muhammad Muzzammil Edhi ◽  
...  

Abstract Objectives Ki67 is the most commonly used marker to evaluate proliferative index in breast cancer, however no cutoff values have been clearly defined for high ki67 index. Cancer management should be according to loco-regional profile; therefore, we aimed to determine ki67 index in 1951 cases of intrinsic breast cancer subtypes and its association with other prognostic parameters in our set up. Results Triple negative breast cancers showed highest ki67 index (mean 50.9 ± 23.7%) followed by Her2neu (mean 42.6 ± 21.6%) and luminal B cancers (mean 34.9 ± 20.05%). Metaplastic and medullary breast cancers significantly showed higher ki67 index as compared to ductal carcinoma, NOS. No significant association of ki67 index was noted with any of the histologic parameters in different subtypes of breast cancer expect for tumor grade. Although, ki67 index is a valuable biomarker in breast cancer, however no independent prognostic significance of ki67 could be established in our study.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4562-4562
Author(s):  
Sonja S. Genadieva Stavric ◽  
Gore G. Zografski ◽  
Ljube L.J. Ivkovski ◽  
Nikola N. Siljanoski ◽  
Borce B. Georgievski ◽  
...  

Abstract Aggressive Non-Hodgkin lymphoma (NHL) is heterogeneous group with respect to clinical, histopatological and evaluative features. The International Prognostic Index (IPI) has provided a widely accepted prognostic set of criteria to design therapy. However, IPI dose not determine whether routine phenotypic features, beside IPI, may influence survival. We evaluate the prognostic significance of Bcl-2 and Ki67 protein expression in relation to clinical presentation and outcome. In the period 1989–2002,two hundred eleven patients with newly diagnosed aggressive NHL were recorded in our Department. In this study we included patients with available biopsy sample. Protein expression was analyzed on paraffin embedded tumor tissue by imunohistochemistry in relation to clinical factor and outcome. The expression of more than 20% of neoplastic cell was considered positive for bcl-2, and more than 60% for Ki-67. Comparison was made by x2 test. Survival curves were considered by Kaplan-Meyer method and compared by the long-rank test. Sixty seven patients were recorded and their characteristic were: median age 53 years, stage III and IV, 67%; present B symptoms 44%,; bone marrow infiltration 29%, elevated LDH 58%, performas status more then 1– 26%; extra nodal sites more than 2 –34%. All 62 patients received antracyclin based combination chemotherapy, 72% CHOP regiment. Overall survival was 52% with a follow up 6–183 months. Bcl-2 expression was observed in 35,5% (22pts) and Ki67 positivity over 60% in 20 pts (30%). Overall survival was influenced by bcl-2 and Kli67 expression. Bcl-2 positive cases were significantly associated with lower overall survival (20% vs. 58%; p<0.01). Overall survuval was significantly worse in patients with Ki67 positivity over 60% (27% vs. 49%; p<0.05) Bcl-2 and Ki67 monoclonal antibody immunostaging appears to be a simple and reproducible method of determining biological potential of tumor cells and provides useful prognostic information in patients with aggressive NHL.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8458 ◽  
Author(s):  
Dalong Sun ◽  
Tiancheng Luo ◽  
Pingping Dong ◽  
Ningping Zhang ◽  
Jing Chen ◽  
...  

Background As the main cellular ingredients of tumor microenvironment, tumor-associated macrophages (TAMs) play a vital role in tumor development and progression. Recent studies have suggested that TAMs are sensitive and specific prognostic factors in numerous cancers. The primary purpose of this study is to determine the prognostic significance of TAMs in intrahepatic cholangiocarcinoma (ICC). Methods Immunohistochemical staining of CD68, CD86 and CD206 were performed in tissue microarrays containing 322 patients, who underwent surgical resection and were pathologically diagnosed with ICC. The prognostic value of CD68, CD86 and CD206 were evaluated by Kaplan–Meier analysis (log-rank test) and nomogram models. Results We demonstrated that the CD86+/CD206+ TAMs model was an independent prognostic index for ICC patients. Patients with low CD86+ TAMs and high CD206+ TAMs infiltration had a markedly worse prognosis and increased risk of post-operative recurrence when compared to high CD86+ TAMs and low CD206+ TAMs intratumoral infiltration. Furthermore, subgroup analysis indicated that the CD86+/CD206+ TAMs model predicted prognosis of ICC patients more powerfully than single macrophage immunomarker. Interestingly, the CD86+/CD206+ TAMs model could further distinguish prognosis of CA-199 negative ICC patients, who were generally presumed to have a more favorable outcome. In order to further perfect the prognostic value of the CD86+/CD206+ TAMs model, we constructed and validated a postoperative nomogram to predict overall survival and recurrence-free survival time in ICC patients. Conclusions These findings indicate that the CD86+/CD206+ TAMs model possess potential value as a novel prognostic indicator for ICC patients.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Adel Alblihy ◽  
Ahmed Shoqafi ◽  
Michael S. Toss ◽  
Mashael Algethami ◽  
Anna E. Harris ◽  
...  

AbstractThe MRE11–RAD50–NBS1 (MRN) complex is critical for genomic stability. Although germline mutations in MRN may increase breast cancer susceptibility, such mutations are extremely rare. Here, we have conducted a comprehensive clinicopathological study of MRN in sporadic breast cancers. We have protein expression profiled for MRN and a panel of DNA repair factors involved in double-strand break repair (BRCA1, BRCA2, ATM, CHK2, ATR, Chk1, pChk1, RAD51, γH2AX, RPA1, RPA2, DNA-PKcs), RECQ DNA helicases (BLM, WRN, RECQ1, RECQL4, RECQ5), nucleotide excision repair (ERCC1) and base excision repair (SMUG1, APE1, FEN1, PARP1, XRCC1, Pol β) in 1650 clinical breast cancers. The prognostic significance of MRE11, RAD50 and NBS1 transcripts and their microRNA regulators (hsa-miR-494 and hsa-miR-99b) were evaluated in large clinical datasets. Expression of MRN components was analysed in The Cancer Genome Atlas breast cancer cohort. We show that low nuclear MRN is linked to aggressive histopathological phenotypes such as high tumour grade, high mitotic index, oestrogen receptor- and high-risk Nottingham Prognostic Index. In univariate analysis, low nuclear MRE11 and low nuclear RAD50 were associated with poor survival. In multivariate analysis, low nuclear RAD50 remained independently linked with adverse clinical outcomes. Low RAD50 transcripts were also linked with reduced survival. In contrast, overexpression of hsa-miR-494 and hsa-miR-99b microRNAs was associated with poor survival. We observed large-scale genome-wide alterations in MRN-deficient tumours contributing to aggressive behaviour. We conclude that MRN status may be a useful tool to stratify tumours for precision medicine strategies.


2003 ◽  
Vol 127 (3) ◽  
pp. e131-e134 ◽  
Author(s):  
Odile David ◽  
Meena Bhattacharjee

Abstract Neuroendocrine differentiation has been reported in both in situ and infiltrating breast cancers. The prognostic significance of neuroendocrine differentiation in mammary carcinoma is unclear. We report a case of infiltrating ductal carcinoma in which there was a morphologically conventional-appearing infiltrating ductal component admixed with nests of cells that resembled a carcinoid tumor and initially mimicked the appearance of intraductal carcinoma. Immunohistochemical stains for synaptophysin and chromogranin demonstrated diffuse, strong positivity uniformly throughout the tumor, even in the more conventional-appearing areas. Electron microscopic examination of tissue retrieved from paraffin blocks was attempted unsuccessfully. We concluded that this was an infiltrating ductal carcinoma with morphologic and immunohistochemical evidence of neuroendocrine differentiation. The case is discussed with a review of the literature and a discussion of nomenclature for tumors of the breast showing variable degrees of neuroendocrine differentiation.


2017 ◽  
Vol 11 ◽  
pp. 117822341774585
Author(s):  
Lakmini Mudduwa ◽  
Harshini Peiris ◽  
Shania Gunasekara ◽  
Deepthika Abeysiriwardhana ◽  
Thusharie Liyanage

Aim: To study the prognostic value of immunohistochemically detected low Claudin3 expression in breast cancers. Methods: This retrospective study included patients with breast cancer who were investigated at our unit from 2006 to 2015. Tissue microarrays were constructed, and immunohistochemical staining was done to assess the Claudin3 expression and to classify breast cancers according to the immunohistochemical surrogates for molecular classification. Kaplan-Meier model and log-rank test were used for recurrence-free survival and breast cancer–specific survival analysis. Results: Of the 853 patients, overall low expression of Claudin3 was seen in 18.4%. Recurrence-free survival of patients with overall low Claudin3 breast cancers was poor in luminal A ( P = .006) and luminal B (Her2−) ( P = .009) subtypes compared with those who had Claudin3 expression in each group. Conclusions: Assessment of Claudin3 expression by immunohistochemistry is suggested for luminal A and luminal B (Her2−) subtypes to identify patients with poor prognosis.


1970 ◽  
Vol 2 (3) ◽  
pp. 198-202
Author(s):  
D Ghartimagar ◽  
A Ghosh ◽  
OP Talwar ◽  
R Narasimhan

Background: Breast cancers rarely occur in young women but are known to have more aggressive behaviors and poorer outcome. We here compare the significance of breast carcinoma in female below the age of 35 to the age over 35 whose specimens were submitted to Manipal teaching hospital, Pokhara. Materials and Methods: All cases of mastectomy with carcinoma from January 2000 to September 2011 were included in the study. Clinical and histopathological datas of all cases were reviewed and collated. Results: A total of 148 mastectomy specimens were received, among which, 23 cases (16%) were below 35 years; whereas 125 cases (84%) were above 35 years of age. In both groups, Stage II was the commonest stage but stage III was much more common in older group (33% versus 9%) and stage I was more common in younger age group (39% versus 27%). Bloom Richardson grading showed that in the older age group, grade 1 is the commonest grade (50%) while in the younger group; grade 3 is the commonest (39%). Patients were followed for a varying period of 6 months to 5 years. Two cases (2% of followed up cases) in older group and 3 cases (15% of followed up cases) in the younger group showed recurrence. Conclusion: Breast carcinoma in the patients younger than 35 years though presented at an early stage has higher grade tumor and poorer outcome. DOI: http://dx.doi.org/10.3126/jpn.v2i3.6021 JPN 2012; 2(3): 198-202


Author(s):  
Yu Wang ◽  
Jiantao Wang ◽  
Haiping Wang ◽  
Xinyu Yang ◽  
Liming Chang ◽  
...  

Objective: Accurate assessment of breast tumor size preoperatively is important for the initial decision-making in surgical approach. Therefore, we aimed to compare efficacy of mammography and ultrasonography in ductal carcinoma in situ (DCIS) of breast cancer. Methods: Preoperative mammography and ultrasonography were performed on 104 women with DCIS of breast cancer. We compared the accuracy of each of the imaging modalities with pathological size by Pearson correlation. For each modality, it was considered concordant if the difference between imaging assessment and pathological measurement is less than 0.5cm. Results: At pathological examination tumor size ranged from 0.4cm to 7.2cm in largest diameter. For mammographically determined size versus pathological size, correlation coefficient of r was 0.786 and for ultrasonography it was 0.651. Grouped by breast composition, in almost entirely fatty and scattered areas of fibroglandular dense breast, correlation coefficient of r was 0.790 for mammography and 0.678 for ultrasonography; in heterogeneously dense and extremely dense breast, correlation coefficient of r was 0.770 for mammography and 0.548 for ultrasonography. In microcalcification positive group, coeffient of r was 0.772 for mammography and 0.570 for ultrasonography. In microcalcification negative group, coeffient of r was 0.806 for mammography and 0.783 for ultrasonography. Conclusion: Mammography was more accurate than ultrasonography in measuring the largest cancer diameter in DCIS of breast cancer. The correlation coefficient improved in the group of almost entirely fatty/ scattered areas of fibroglandular dense breast or in microcalcification negative group.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dechuang Jiao ◽  
Jingyang Zhang ◽  
Jiujun Zhu ◽  
Xuhui Guo ◽  
Yue Yang ◽  
...  

Abstract Background Previous studies have reported poor survival rates in inflammatory breast cancer (IBC) patients than non-inflammatory local advanced breast cancer (non-IBC) patients. However, until now, the survival rate of IBC and other T4 non-IBC (T4-non-IBC) patients remains unexplored. Methods Surveillance, Epidemiology, and End Results (SEER) database was searched to identify cases with confirmed non-metastatic IBC and T4-non-IBC who had received surgery, chemotherapy, and radiotherapy between 2010 and 2015. IBC was defined as per the American Joint Committee on Cancer (AJCC) 7th edition. Breast Cancer-Specific Survival (BCSS) was estimated by plotting the Kaplan-Meier curve and compared across groups by using the log-rank test. Cox model was constructed to determine the association between IBC and BCSS after adjusting for age, race, stage of disease, tumor grade and surgery type. Results Out of a total of 1986 patients, 37.1% had IBC and mean age was 56.6 ± 12.4. After a median follow-up time of 28 months, 3-year BCSS rate for IBC and T4-non-IBC patients was 81.4 and 81.9%, respectively (log-rank p = 0.398). The 3-year BCSS rate in HR−/HER2+ cohort was higher for IBC patients than T4-non-IBC patients (89.5% vs. 80.8%; log-rank p = 0.028), and in HR−/HER2- cohort it was significantly lower for IBC patients than T4-non-IBC patients (57.4% vs. 67.5%; log-rank p = 0.010). However, it was identical between IBC and T4-non-IBC patients in both HR+/HER2- (85.0% vs. 85.3%; log-rank p = 0.567) and HR+/HER2+ (93.6% vs. 91.0%, log-rank p = 0.510) cohorts. After adjusting for potential confounding variables, we observed that IBC is a significant independent predictor for survival of HR−/HER2+ cohort (hazards ratio [HR] = 0.442; 95% CI: 0.216–0.902; P = 0.025) and HR−/HER2- cohort (HR = 1.738; 95% CI: 1.192–2.534; P = 0.004). Conclusions Patients with IBC and T4-non-IBC had a similar BCSS in the era of modern systemic treatment. In IBC patients, the HR−/HER2+ subtype is associated with a better outcome, and HR−/HER2- subtype is associated with poorer outcomes as compared to the T4-non-IBC patients.


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