scholarly journals Diagnostic performance of superb microvascular imaging combined with shear-wave elastography in distinguishing invasive ductal carcinoma molecular subtypes

Author(s):  
Fengjiao Chen ◽  
Hui Jing ◽  
Haitao Shang ◽  
Haoyan Tan ◽  
Haobo Yang ◽  
...  

IntroductionTo explore the diagnostic value of combining superb microvascular imaging (SMI), shear-wave elastography (SWE), and Breast Imaging Reporting and Data System (BI-RADS) to distinguish different molecular subtypes of invasive ductal carcinoma (IDC).Material and methodsA total of 239 surgically confirmed IDC masses in 201 patients underwent conventional ultrasound, SMI, and SWE examination, the information such as echo pattern, posterior features, margins, SMI pixels, and hardness of the masses was recorded. According to the St. Gallen standard, breast masses were classified as Luminal A, Luminal B, HER2 overexpression, and triple-negative subtype. We further explored the differences between different molecular subtypes of IDC.ResultsLuminal A subtype had the following characteristics: low histologic grade, posterior acoustic shadowing (p= 0.019), spiculated margins (p<0.001) , and relatively soft. Luminal B subtype was characterized by low histological grade (p <0.0001), posterior acoustic shadowing or indifference, and indistinct margins. HER2 overexpression breast cancers were characterized by high histological grade, enhanced posterior acoustics or indifference, calcifications (p= 0.005), spiculated or indistinct margins, vascularity (p=0.005), and relative stiffness. Triple-negative breast cancers had the characteristics of high histological grade, posterior echogenic enhancement, lack of calcifications, circumscribed or microlobulated margins, low blood flow signals, and stiff tissue (p=0.013).ConclusionsOur study demonstrated the significant differences and trends among the IDC four subtypes by the combined application of SMI, SWE, and BI-RADS lexicon, which are of great significance for early diagnosis, selection of treatment methods, and evaluation of prognosis of IDC.

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Charity Ameh-Mensah ◽  
Babatunde Moses Duduyemi ◽  
Kweku Bedu-Addo ◽  
Elijah Atta Manu ◽  
Francis Opoku ◽  
...  

Background. Little is known about the role of apoptosis in the tumorigenesis and prognosis of breast cancer in Ghana. Chemotherapeutic drug efficacy partially relates to apoptosis induction, rendering it a vital target in cancer therapy with unique biomarker opportunities that have not been exploited. Aberrations in this pathway are central to tumorigenesis, tumor progression, overall tumor growth, and regression during treatment therapies. Antiapoptotic bcl-2 (gene) and p53 are known to play roles in apoptosis while Ki-67 is a proliferative marker. The aim of our study is to determine the association of bcl-2 (protein) with p53 and Ki-67 in 203 consecutive breast cancer cases over a 10-year period. Method. A retrospective cross-sectional study on archival FFPE tissue blocks over a 9-year period with abstraction of clinicopathologic data. Two hundred and three consecutive and suitable FFPE blocks were selected for tissue microarray (TMA) construction, and IHC (bcl-2 (protein), Ki-67, p53, cyclin D, pan cytokeratins A and E, ER, PR, and HER2/neu) was done. Expressions of bcl-2 (protein), p53, and Ki-67 were related to histological grade, lymphovascular invasion, and molecular subtypes. SPSS version 23 was used to analyze results. Results. Most of our cases were in the fifth decade of life (31%); invasive carcinoma of no special type (NST) was predominant (87%); histological grade III (38%) was the highest; and Luminal A (19.8%), Luminal B (9.9%), HER2 (16%), and TNBC (54.3%) constituted the molecular classes. bcl-2 expression was found in 38% of the cases. Our cases also showed mutation in p53 (36.7%) and ki-67 expression (62.5%). bcl-2 (protein) and p53 significantly correlated with Luminal B and TNBC ( p < 0.01 ). Ki-67 also correlated significantly with Luminal A and B and HER2 overexpression ( p < 0.01 ). Premenopausal age (40–49) and histological grade inversely correlated with bcl-2 (protein) expression. p53 statistically correlated with Ki-67 ( p < 0.05 ). Conclusion. Our results show high expression of bcl-2 (protein) suggesting an important role of apoptosis in Ghanaian breast cancer cases. bcl-2 (protein), p53, and Ki-67 expressions emerged interdependently from this research and can thus be manipulated in prediction and prognosis of breast cancers in our setting.


Author(s):  
Iris Rabinovich ◽  
Ana Paula Martins Sebastião ◽  
Rubens Silveira Lima ◽  
Cícero de Andrade Urban ◽  
Eduardo Schunemann Junior ◽  
...  

Breast cancer is a very heterogeneous disease. The intrinsic molecular subtypes can explain the intertumoral heterogeneity and the cancer stem cell (CSC) hypothesis can explain the intratumoral heterogeneity of this kind of tumor. CD44+/CD24- phenotype and ALDH1 expression are the major CSC markers described in invasive breast cancer. In the present study, 144 samples of invasive breast carcinoma, no special type were distributed in 15 tissue microarrays (TMA) and then evaluated for expression of the CD44+/CD24- phenotype and ALDH1 to understand the importance of these CSC markers and the clinical aspects of breast cancer. The samples were classified into four molecular subtypes according to clinicopathological criteria: Luminal A, Luminal B, HER2, and Basal-like. A statistical association was found between the molecular subtypes and the CSC markers, with HER2 the most frequent subtype for both markers. ALDH1 was also associated with other poor prognostic variables, such as a high histological grade and larger tumors, but it was not associated with the patients’ prognosis in this sample and nor was the CD44+/CD24- phenotype in a multivariate analysis. There are still many controversies about the role of these markers in breast cancer molecular subtypes. The identification of these populations of cells, through immunohistochemical markers, can help to better understand the CSC theory in clinical practice and, in the near future, contribute to developing new target therapies.    


BMJ Open ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. e021819
Author(s):  
Qin Li ◽  
Li Li ◽  
Xiaoyue Jiang ◽  
Qi Du ◽  
Yingrui Li ◽  
...  

ObjectivesThis study investigated the characteristics and prognostic values of traditional pathological parameters and advanced molecular subtypes in women with operable breast cancer in Beijing.DesignA retrospective study through case information enquiry or telephonic follow-up.SettingBeijing Friendship Hospital.Participants1042 patients with primary operable breast cancer between 2008 and 2012 were enrolled in the study.MeasuresThe characteristics and 5-year relapse rates according to the Nottingham Prognosis Index (NPI) and molecular subtypes were analysed.ResultsIn 1042 patients, the percentages of high histological grade, N1+N2, T2+T4 were 7.3%, 24.2%, 46.9%, respectively. In patients with invasive breast cancer, the percentages of auxiliary staging, positive margins, vascular invasion and nerve infiltration were 65.0%, 2.8%, 10.5% and 1.1%, respectively. The missing percentages of auxiliary staging, margins, vascular tumour invasion and nerve infiltration were 14.2%, 31.4%, 46.5% and 97.4%, respectively. The percentages of ER-positive, PR-positive, HER2-positive and Ki-67 high expression were 64.3%, 43.8%, 18.8% and 62.7%, respectively. The percentages of luminal A, luminal B, HER2-overexpression and basal-like breast cancers were 10.5%, 54.2%, 8.2% and 11.2%, respectively. Luminal A, luminal B and basal-like breast cancer subtypes were more common in the >60 years group, the 41–60 years group and the 20–40 years group, respectively. The 5-year relapse rates according to NPI were as follows: 6.2% in the low recurrence risk group, 10.4% in the moderate recurrence risk group and 12.9% in the high recurrence risk group. The 5-year relapse rates according to molecular subtypes were as follows: luminal A 4.0%, luminal B 7.0%, HER2-overexpression14.2%, basal-like 15.6%.ConclusionsReasonable analysis of traditional pathological parameters and advanced molecular subtypes in women with operable breast cancer in Beijing may be useful to guide precise treatment and predict prognosis.


Author(s):  
Ana Paula Almeida Miranda Reis ◽  
Cecilma Miranda de Sousa Teixeira ◽  
Adriano Rêgo Lima de Medeiros ◽  
Karlla Zolinda Cantão Chaves ◽  
Camila Rosa de Albuquerque ◽  
...  

Abstract Objective To evaluate the distribution of the main sociodemographic and clinical-pathological characteristics in women with breast cancer according to the molecular profile by immunohistochemistry. Methods A cross-sectional, retrospective, analytical and quantitative study was performed, with an analysis of 137 medical records from January 2015 to December 2018 of women attending the High Complexity in Oncology Unit of the city of Imperatriz, state of Maranhão, Brazil. The immunohistochemical profile of tumors based on the estrogen and progesterone receptor, Human Epidermal growth factor Receptor-type 2 (HER2) overexpression and Ki67 cell proliferation index was defined, from which six molecular subtypes were determined: luminal A, luminal B-HER2 negative, luminal B-HER2 positive, triple negative, overexpression of HER2 and inconclusive. Results A total of 52.6% of the patients were postmenopausal, mean age 52.1 years old, brown (56.2%), had a schooling level < 9 years (40%), staging > IIB (52.6%) and 23.4% had metastasis. Invasive ductal carcinoma accounted for 84.7%, tumor size was 2 to 5 cm (48.9%), with lymph node involvement (56.2%), axillary lymphadenectomy in 67.2%, and mastectomy in 73.7% of the patients. The most frequent molecular subtype was the luminal B-HER2 negative (36.5%), and the luminal A subtype showed characteristics of better prognosis when compared with the others. Conclusion It was concluded that in the association of molecular subtypes with sociodemographic and clinical-pathological characteristics, there were no statistically significant results obtained, except for complementary therapy, referring to hormone therapy, and there was a high index of metastasis at diagnosis, which was a worrying factor and indicative of failures in the screening and early diagnosis of this population.


2013 ◽  
Vol 20 (3) ◽  
pp. 339-348 ◽  
Author(s):  
Sewha Kim ◽  
Do Hee Kim ◽  
Woo-Hee Jung ◽  
Ja Seung Koo

The aim of this study was to investigate the expression of glutamine metabolism-related proteins to determine whether glutamine is metabolized differently according to breast cancer molecular subtype. We generated a tissue microarray of 702 breast cancer patients and performed immunohistochemical staining for glutamine metabolism-related proteins, including glutaminase 1 (GLS1 (GLS)), glutamate dehydrogenase (GDH (H6PD)), and amino acid transporter-2 (ASCT2 (SLC1A5)), which were separately evaluated in tumor and stroma compartments and then analyzed by breast cancer molecular subtypes. Breast cancers were classified as follows: 293 luminal A (41.7%), 166 luminal B (23.6%), 67 HER2 type (9.6%), and 176 TNBC (25.1%). HER2 type showed the highest stromal GLS1 (P=0.001), tumoral GDH (P=0.001), stromal GDH (P<0.001), and tumoral ASCT (P<0.001) expression. We identified differential expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer. The highest glutamine metabolic activity was seen in HER2-type breast cancer.


2021 ◽  
Vol 24 (11) ◽  
pp. 837-844
Author(s):  
Mehreen Mushtaq ◽  
Summaya Sohail Chaudry ◽  
Ahmareen Khalid Sheikh ◽  
Nazia Khan ◽  
Asma Khattak ◽  
...  

Background: Ki-67 is a proliferation marker that is used not only to categorize patients in luminal A and B subtypes of breast cancers, but also to determine the aggressiveness of the disease in triple negative and human epidermal growth factor 2 (HER2) over expressed molecular subtypes. The present study was designed to evaluate the role of Ki-67 with cut off value of 14% in molecular subgroups and its association with patient prognosis. Methods: Immunostaining was performed on histopathologically confirmed sections (n = 278) to assess expression of Ki-67, estrogen receptor (ER), progesterone receptor (PR) and HER2. Immunoreactivity of molecules was recorded as percentage scoring. Results: Adopting a cut off value of 14%, Ki-67 was high in 88%of the cases included in the study. High Ki-67 was significantly associated with pathological parameters including histological grade, advanced stage and nodal/distant metastasis. Immunoexpression of ER, PR and HER2 also showed strong correlation with high expression of Ki-67. Based on the St. Gallen classification, the cases were categorized into luminal A (10%) and luminal B (51%), triple negative (20%) and HER2 enriched (18%). Ki-67 index was also significantly high in 98% of HER2 enriched and 95% of TNBC patients. Interestingly, Ki-67 score with cut off value of 14% proved to be significant in deciphering prognosis in luminal patients. Moreover, high expression of Ki-67 also proved to be a marker of poor prognosis, especially in triple negative patients. Conclusion: We suggest that utilization of IHC4 status i.e. ER, PR, HER2 and Ki-67 along with pathological findings and molecular subtyping can considerably affect clinical as well as therapeutic decisions.


2021 ◽  
Author(s):  
Dorsay Sadeghian ◽  
Hana Saffar ◽  
Pouya Mahdavi Sharif ◽  
Vahid Soleimani ◽  
Behnaz Jahanbin

Abstract Background: Currently, breast cancers are divided into four major molecular subtypes. The distinction between the luminal A and luminal B subtypes is mainly based on the cellular proliferation indices and is assessed by the Ki-67 scoring. Due to the limitations in the assessment and expression of Ki-67, we hypothesized that minichromosome maintenance protein 6 (MCM6) can be taken as a surrogate marker to differentiate molecular subtypes and aid in more precise grading of tumors. Methods: We performed a retrospective, cross-sectional study on 124 samples of breast cancer and 40 samples of normal breast tissue. Relevant clinical information was retrieved from the relevant Cancer Institute database.Results: MCM6 could discriminate between different histologic grades. The luminal B subtype exhibited a higher MCM6 score in comparison to luminal A (P=0.01). There were significantly higher MCM6 scores in the hormone receptor (HR) negative, in comparison to luminal breast cancers (P<0.001). MCM6 score had a significant correlation with the mitotic count (P<0.001).Conclusion: MCM6 can reliably differentiate luminal A and luminal B subtypes and was correlated with the mitotic counts. More studies are needed to standardize its assessment methods, determine more robust cut-off values, and evaluate its associations with prognostic features of breast cancer.


Author(s):  
Gulten Sezgın ◽  
Melda Apaydın ◽  
Demet Etıt ◽  
Murat Kemal Atahan

Background and aim. In medical practice the classification of breast cancer is most commonly based on the molecular subtypes, in order to predict the disease prognosis, avoid over-treatment, and provide individualized cancer management. Tumor size is a major determiner of treatment planning, acting on the decision-making process, whether to perform breast surgery or administer neoadjuvant chemotherapy. Imaging methods play a key role in determining the tumor size in breast cancers at the time of the diagnosis. We aimed to compare the radiologically determined tumor sizes with the corresponding pathologically determined tumor sizes of breast cancer at the time of the diagnosis, in correlation with the molecular subtypes. Methods. Ninety-one patients with primary invasive breast cancer were evaluated. The main molecular subtypes were luminal A, luminal B, HER-2 positive, and triple-negative. The Bland–Altman plot was used for presenting the limits of agreement between the radiologically and the pathologically determined tumor sizes by the molecular subtypes. Results. A significantly proportional underestimation was found for the luminal A subtype, especially for large tumors. The p-values for the magnetic resonance imaging, mammography, and ultrasonography were 0.020, 0.030, and <0.001, respectively. No statistically significant differences were observed among the radiologic modalities in determining the tumor size in the remaining molecular subtypes (p > 0.05). Conclusion. The radiologically determined tumor size was significantly smaller than the pathologically determined tumor size in the luminal A subtype of breast cancers when measured with all three imaging modalities. The differences were more prominent with ultrasonography and mammography. The underestimation rate increases as the tumor gets larger.


Mastology ◽  
2020 ◽  
Vol 30 (Suppl 1) ◽  
Author(s):  
Vanessa Monteiro Sanvido ◽  
Morgana Domingues da Silva ◽  
Patricia Zaideman Charf ◽  
Gil Facina ◽  
Afonso Celso Pinto Nazário

Introduction: Invasive breast carcinoma represents a heterogeneous group of lesions that differ in their molecular and histological characteristics. Perou et al. evaluated breast tumors using the DNA microarray technique and classified them into four molecular subtypes: Luminal A (LA), Luminal B (LB), HER2 overexpression (HER2), and triple-negative (TN). Immunohistochemistry approximately identifies the subtypes. The TN subtype is negative for estrogen and progesterone receptors and HER2 protein. This subgroup is comprehensive, with 75% of them being basaloid, that is, cells with a molecular profile similar to that of myoepithelial cells and a high expression 5, 6, 14, and 17 cytokeratins, vimentin, and P-cadherin. These tumors tend to be more aggressive, have higher rates of cell proliferation, and, therefore, a worse prognosis. Clinically, triple-negative carcinomas are more strongly associated with younger patients, early local and distant recurrence. Given their rapid progression, they can be clinically diagnosed in the interval of screening tests. Objective: To compare clinical and radiological aspects of TN and other molecular subtypes of breast cancer at diagnosis. Method: The study retrospectively evaluated data collected from medical records of patients diagnosed with breast cancer and treated at the Hospital São Paulo from 2013 to 2016. Results: In the study period, 235 cases of breast cancer were diagnosed. The incidence in patients under 39 years was 4.2% for LA, 4.9% for LB, and 8.3% for TN. At diagnosis, 83% of patients with TN tumors had clinical complaints, of which 96% were nodules. In mammographies, TN presented as nodules in 100% of cases, LA in 68%, LB in 71%, and HER2 in 50%. Microcalcifications were identified in 14% of LA cases, 21% of LB, and 50% of HER2. TN had no cases of microcalcifications or asymmetries. Among the other subtypes, the diagnosis by physical examination represented 35% to 53% of cases. As to the staging at diagnosis, TN cases presented ≤2 cm tumors in 25% of cases. The LA, LB, and HER2 subtypes presented as ≤2 cm tumors, respectively, in 61%, 49.4%, and 43% of patients. Lymph node involvement by neoplasm at diagnosis occurred in 3.35%, 17.5%, 14.3%, and 33.3% of LA, LB, HER2, and TN cases, respectively. Conclusion: TN carcinomas affect a greater number of young patients, outside the screening age group. In our sample, TN tumors were diagnosed based on clinical complaints and showed no association with non-palpable breast lesions. TN is the subtype with the highest probability of interval tumors, untraceable by conventional exams, and, as a result, other screening options, such as serum assays, have been discussed.


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