scholarly journals Expression of Tumour-Associated MUC1 Is a Poor Prognostic Marker in Breast Cancer in Kumasi, Ghana

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
E. Atta Manu ◽  
K. Bedu-Addo ◽  
N. A. Titiloye ◽  
C. Ameh-Mensah ◽  
F. Opoku ◽  
...  

Background. Immunohistochemical assessment of breast cancer and stratification into the basic molecular subtypes afford a much deeper insight into the biology of breast cancer, while presenting with opportunities to exploit personalized, targeted treatment. Traditionally, the oestrogen, progesterone, and epidermal growth factor receptors are assessed. MUC1, a transmembrane mucin, has been demonstrated a potential prognostic and metastatic marker in breast cancer. However, there have been a limited number of studies addressing the predictive and prognostic features of MUC1 in African breast cancer. This study aims at addressing the expression profiles of MUC1 and other biomarkers in Ghanaian breast cancer and determines its predictive and prognostic characteristics, in relation to other clinicopathological features. Methods. Haematoxylin and eosin (H&E) slides of breast cancer cases were reviewed and 203 suitable cases were selected for tissue microarray (TMA) construction and immunohistochemistry. Anti-ER, PR, HER2, Ki-67, and MUC1 antibodies were used. Results from the immunostaining were analysed using SPSS version 23. Results. About 59% of cases expressed MUC1. Majority of cases in the study showed a lack of expression of all three traditional markers (29% expressed ER, 10.9% PR, and 20.7% HER2). Ki-67 index were 62.1% (low), 16.5% (moderate), and 21.4% (high). MUC1 expressions among the molecular classes were luminal A (60.7%), luminal B (68.8%), HER2 overexpression (87.5%), and triple negative (56.6%). There were significant associations between MUC1 and HER2 overexpression (p=0.01) and triple negative (p<0.01). Conclusion. The high proportion of breast cancer cases expressing MUC1, as well as its association with the two most aggressive molecular classes, indicate a substantial role in the biology of breast cancer in our cohort, and it is an indication of poor prognosis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14285-e14285
Author(s):  
Linxiaoxi Ma ◽  
Liang Guo ◽  
Shyamal Goswami ◽  
Xiaoming Zhang ◽  
Jiong Wu

e14285 Background: The treatment of breast cancer, one of the most common malignant tumors for female, focuses on the combined treatments based on subtypes including Luminal A, Luminal B, HER2 overexpression and triple negative. Given that none of those subtypes takes into consideration of immunological parameters, it is valuable to explore the biological characteristics and prognostic value of immune cells in breast caner. T follicular helper cells (Tfh cells) have been identified in different types of tumors with rare datas in breast cancer. One of them indicated the positive prognostic value of 8-gene Tfh signature. Exploration of Tfh cells may provide new clues to the potential immunotherapies in breast cancer. Methods: Freshly resected invasive breast cancer tissue from Fudan University Shanghai Cancer Center were collected during 06/2015 to 05/2017. Patients were divided into Luminal A (N = 61), Luminal B (HER2-) (N = 138), Luminal B (HER2+) (N = 72), HER2+ (non-luminal) (N = 57) and triple negative (N = 58) based on St Gallen International Expert Consensus. Results: A subpopulation of PD1hiCD4+ T cells in the tumor tissues of breast cancer was identified as Tfh-like cells, with the specific expression of Bcl-6 and CXCL13, confirmed by IHC. Phenotypes of those cells were checked by flow cytometry. Tfh-like cells were of a high level of ICOS but negative for CXCR5, suggesting that they were atypical Tfh cells. Data showed that high grade (N = 166; mean±SEM, 17.62±0.87) compared with low grade (N = 220; mean±SEM, 12.41±0.46) or high Ki-67 level (N = 300; mean±SEM, 15.38±0.58) with low Ki-67 level (N = 86; mean±SEM, 12.10±0.67), and negative ER expression (N = 115; mean±SEM, 17.47±1.05) compared with positive ER expression (N = 271; mean±SEM, 13.46±0.50) or negative PR expression (N = 177; mean±SEM, 16.87±0.83) compared with positive PR expression (N = 209; mean±SEM, 12.77±0.50) was associated with higher frequency of Tfh-like cells (P < 0.01 to all). Patients with triple negative had higher frequency of Tfh-like cells than those with Luminal A (difference, 6.83; P = 0.0006) and Luminal B (HER2-) (difference, 4.61; P = 0.0124). Patients with HER2+ (non-luminal) had higher frequency of Tfh-like cells than those with Luminal A (difference, 5.34; P = 0.0146). These results indicate that higher frequency of Tfh-like cells could have negative prognostic influence. Conclusions: Our study defined a PD1hiBcl6+CXCL13+CD4+ T cell subpopulation, which specifically secretes cytokine IL-21 as Tfh-like cells. Higher frequency of Tfh-like cells is more likely to be seen in patients with poor prognosis.


Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 837
Author(s):  
So-Woon Kim ◽  
Jinah Chu ◽  
Sung-Im Do ◽  
Kiyong Na

Background and Objectives: Kidney and brain protein (KIBRA) is a protein encoded by the WW and C2 domain containing 1 (WWC1) gene and is involved in the Hippo signaling pathway. Recent studies have revealed the prognostic value of KIBRA expression; however, its role in breast cancer remains unclear. The aim of this study was to examine KIBRA expression in relation to the clinical and pathological characteristics of patients with breast cancer and to disease outcomes. Materials and Methods: We analyzed the expression of KIBRA and its correlation with event-free survival (EFS) outcomes in resected samples from 486 patients with breast cancer. Results: KIBRA expression was significantly different among the molecular subgroups (low KIBRA expression: luminal A, 46.7% versus 50.0%, p = 0.641; luminal B, 32.7% versus 71.7%, p < 0.001; human epidermal growth factor receptor 2 (HER2)-enriched, 64.9% versus 45.5%. p = 0.001; triple-negative, 73.6% versus 43.8%, p < 0.001). Low KIBRA expression was also associated with high nuclear grade (60.4% versus 37.8%, p < 0.001), high histologic grade (58.7% versus 37.0%, p < 0.001), and estrogen receptor (ER) negativity (54.2% versus 23.6%, p < 0.001). Low KIBRA expression was significantly associated with poor EFS (p = 0.041; hazard ratio (HR) 1.658; 95% confidence interval (CI), 1.015–2.709). Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542–10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. In particular, our data highlight KIBRA expression status as a potential prognostic marker for TNBC.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Alexey Surov ◽  
Yun-Woo Chang ◽  
Lihua Li ◽  
Laura Martincich ◽  
Savannah C. Partridge ◽  
...  

Abstract Background Radiological imaging plays a central role in the diagnosis of breast cancer (BC). Some studies suggest MRI techniques like diffusion weighted imaging (DWI) may provide further prognostic value by discriminating between tumors with different biologic characteristics including receptor status and molecular subtype. However, there is much contradictory reported data regarding such associations in the literature. The purpose of the present study was to provide evident data regarding relationships between quantitative apparent diffusion coefficient (ADC) values on DWI and pathologic prognostic factors in BC. Methods Data from 5 centers (661 female patients, mean age, 51.4 ± 10.5 years) were acquired. Invasive ductal carcinoma (IDC) was diagnosed in 625 patients (94.6%) and invasive lobular carcinoma in 36 cases (5.4%). Luminal A carcinomas were diagnosed in 177 patients (28.0%), luminal B carcinomas in 279 patients (44.1%), HER 2+ carcinomas in 66 cases (10.4%), and triple negative carcinomas in 111 patients (17.5%). The identified lesions were staged as T1 in 51.3%, T2 in 43.0%, T3 in 4.2%, and as T4 in 1.5% of the cases. N0 was found in 61.3%, N1 in 33.1%, N2 in 2.9%, and N3 in 2.7%. ADC values between different groups were compared using the Mann–Whitney U test and by the Kruskal-Wallis H test. The association between ADC and Ki 67 values was calculated by Spearman’s rank correlation coefficient. Results ADC values of different tumor subtypes overlapped significantly. Luminal B carcinomas had statistically significant lower ADC values compared with luminal A (p = 0.003) and HER 2+ (p = 0.007) lesions. No significant differences of ADC values were observed between luminal A, HER 2+ and triple negative tumors. There were no statistically significant differences of ADC values between different T or N stages of the tumors. Weak statistically significant correlation between ADC and Ki 67 was observed in luminal B carcinoma (r = − 0.130, p = 0.03). In luminal A, HER 2+ and triple negative tumors there were no significant correlations between ADC and Ki 67. Conclusion ADC was not able to discriminate molecular subtypes of BC, and cannot be used as a surrogate marker for disease stage or proliferation activity.


2013 ◽  
Vol 7 ◽  
pp. BCBCR.S10701 ◽  
Author(s):  
Kristiina Joensuu ◽  
Marjut Leidenius ◽  
Mia Kero ◽  
Leif C. Andersson ◽  
Kathryn B. Horwitz ◽  
...  

Breast cancer can recur even decades after the primary therapy. Markers are needed to predict cancer progression and the risk of late recurrence. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), proliferation marker Ki-67, and cytokeratin CK5 were studied to find out whether their expression or occurrence in subgroups of breast cancers correlated with the time of recurrence. The expression of HER2, ER, PR, Ki-67, and CK5 was studied by IHC in 72 primary breast cancers and their corresponding recurrent/metastatic lesions. The patients were divided into three groups according to the time of the recurrence/metastasis: before two years, after 5 years, and after 10 years. Based on their IHC profiles, the tumors were divided into surrogates of the genetically defined subgroups of breast cancers and the subtype definitions were as follows: luminal A (ER or PR+HER2–), luminal B (ER or PR+HER2+), HER2 overexpressing (ER–PR–HER2+), triple-negative (ER–PR–HER2–), basal-like (ER–PR–HER2–CK5+), non-classified (ER–PR–HER2–CK5–) and luminobasal (ER or PR+CK5+). In multivariate analysis, tumor size and HER2 positivity were a significant risk of early cancer relapse. The metastases showed a significantly lower CK5 expression. CK5 positivity distinguished triple negative tumors into rapidly and slowly recurring cancers. The IHC subtype ER or PR+HER2– luminal A presented a significantly lower risk of early tumor recurrence. Ki-67 expression denoted early-relapsing tumors and correlated linearly with tumor progression, since Ki-67 positivity declined gradually from early-relapsing toward late-recurring cancers.


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.


2020 ◽  
pp. 1103-1113
Author(s):  
Neslihan Cabioğlu ◽  
Sibel Özkan Gürdal ◽  
Arda Kayhan ◽  
Nilüfer Özaydın ◽  
Cennet Şahin ◽  
...  

PURPOSE The Turkish Bahçeşehir Breast Cancer Screening Project was a 10-year, organized, population-based screening program carried out in Bahçeşehir county, Istanbul. Our aim was to examine the biologic features and outcome of screen-detected and interval breast cancers during the 10-year study period. METHODS Between 2009 and 2019, 2-view mammograms were obtained at 2-year intervals for women aged 40 to 69 years. Clinicopathological characteristics including ER, PR, HER2-neu, and Ki-67 status were analyzed for those diagnosed with breast cancer. RESULTS In 8,758 screened women, 131 breast cancers (1.5%) were detected. The majority of patients (82.3%) had prognostic stage 0-I disease. Contrarily, patients with interval cancers (n = 15; 11.4%) were more likely to have a worse prognostic stage (II-IV disease; odds ratio [OR], 3.59, 95% CI, 0.9 to 14.5) and high Ki-67 scores (OR, 3.14; 95% CI, 0.9 to 11.2). Interval cancers detected within 1 year were more likely to have a luminal B (57.1% v 31.9%) and triple-negative (14.3% v 1%) subtype and less likely to have a luminal A subtype (28.6% v 61.5%; P = .04). Patients with interval cancers had a poor outcome in 10-year disease-specific (DSS) and disease-free survival (DFS) compared with those with screen-detected cancers (DSS: 68.2% v 98.1%, P = .002; DFS: 78.6% v 96.5%, P = .011). CONCLUSION Our findings suggest the majority of screen-detected breast cancers exhibited a luminal A subtype profile with an excellent prognosis. However, interval cancers were more likely to have aggressive subtypes such as luminal B subtype or triple-negative cancers associated with a poor prognosis requiring other preventive strategies.


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.


2021 ◽  
Vol 9 (1) ◽  
pp. 15-22
Author(s):  
Yosef Yantamajaya Simbolon

Pendahuluan: Kanker payudara seharusnya dapat ditemukan pada tahap yang lebih dini, akan tetapi kanker ini lebih sering diketahui pada stadium lanjut yang menyebabkan tingginya angka kematian. Prognosis kanker yang buruk akan mempengaruhi kualitas hidup pasien, kondisi keuangan, peran dan fungsi pasien dan keluarga bahkan kematian. Acuan prognosis  pada pasien kanker payudara didasarkan pada analisa penanda biologis tumor primer yang mencakup reseptor estrogen (ER), reseptor progesteron (PR), Human Epidermal Growth Factor Receptor 2 (HER2) dan Ki67 yang diklasidikasikan menjadi 4 subtipe molekuler yaitu Luminal A, Luminal B, HER2 overexpression, dan Triple Negative. Metode: Jenis penelitian ini menggunakan metode studi systematic review dengan data yang akan digunakan adalah hasil-hasil penelitian yang telah beredar di dunia. Populasi penelitian ini adalah literatur jurnal hasil pencarian mengenai infiltrasi limfovaskular terhadap subtipe molekuler dari kanker payudara yang dipublikasikan di jurnal internasional dan dapat diakses melalui internet. Sampel penelitian ini ditentukan berdasarkan beberapa kriteria inklusi dan eksklusi yang telah dibuat. Hasil: Dari 5 jurnal internasional yang telah dikumpulkan, selanjutnya dianalisis menggunakan forest plot. Berdasarkan analisis data, didapatkan P =0,21 yang artinya uji perbedaan subkelompok menunjukkan bahwa tidak ada efek subkelompok yang signifikan terjadi secara statistik. Simpulan: Tidak terdapat hubungan antara infiltrasi limfovaskular dengan subtipe molekuler kanker payudara invasif.


ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Jianyi Li ◽  
Shi Jia ◽  
Wenhai Zhang ◽  
Yang Zhang ◽  
Xiang Fei ◽  
...  

Background. Immunohistochemical markers were often used to classify breast cancer into subtypes. The aim of this study was to estimate death and tumor progression for patients with the major subtypes of breast cancer as classified using immunohistochemical assay and to investigate the patterns of benefit from the therapies over the past years. Methods. The study population included primary, operable 199 invasive ductal breast cancer patients, with the median age of 51.1 years old. All patients underwent local and/or systemic treatments. The clinicopathological characteristics and clinical outcomes were retrospectively reviewed. The expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki67 was analyzed by immunohistochemistry. All patients were classified into the following categories: luminal A, luminal B, HER2 overexpression, and triple-negative subtypes. Result. The median follow-up time was 33 months. Luminal A tumors had the lowest rate of tumor progression (0%, P=0.006), while luminal B, HER2 over-expression, and triple-negative subtypes were associated with an increased risk of tumor progression (15.4, 19.2, 15.4%). Clinicopathological subtypes retained independent prognostic significance (P=0.008). There were significant differences by Cox model analyzed in age, menopause, lymph node metastasis, and HER2 for the event of death and tumor progression (P<0.05), and there were significant differences only in chemotherapy for the event, respectively (P<0.05). Conclusion. Clinicopathological subtypes of breast cancer could robustly identify the risk of death and tumor progression and were significant in making therapeutic decision. HER2 was the important poor indicator. The chemotherapy intensity would be enhanced for patients with luminal B, especially for HER2 over-expression subgroup.


2015 ◽  
Vol 33 (20) ◽  
pp. 2254-2261 ◽  
Author(s):  
Erica T. Warner ◽  
Rulla M. Tamimi ◽  
Melissa E. Hughes ◽  
Rebecca A. Ottesen ◽  
Yu-Ning Wong ◽  
...  

Purpose To evaluate the relationship between race/ethnicity and breast cancer–specific survival according to subtype and explore mediating factors. Patients and Methods Participants were women presenting with stage I to III breast cancer between January 2000 and December 2007 at National Comprehensive Cancer Network centers with survival follow-up through December 2009. Cox proportional hazards regression was used to compare breast cancer–specific survival among Asians (n = 533), Hispanics (n = 1,122), and blacks (n = 1,345) with that among whites (n = 14,268), overall and stratified by subtype (luminal A like, luminal B like, human epidermal growth factor receptor 2 type, and triple negative). Model estimates were used to derive mediation proportion and 95% CI for selected risk factors. Results In multivariable adjusted models, overall, blacks had 21% higher risk of breast cancer–specific death (hazard ratio [HR], 1.21; 95% CI, 1.00 to 1.45). For estrogen receptor–positive tumors, black and white survival differences were greatest within 2 years of diagnosis (years 0 to 2: HR, 2.65; 95% CI, 1.34 to 5.24; year 2 to end of follow-up: HR, 1.50; 95% CI, 1.12 to 2.00). Blacks were 76% and 56% more likely to die as a result of luminal A–like and luminal B–like tumors, respectively. No disparities were observed for triple-negative or human epidermal growth factor receptor 2–type tumors. Asians and Hispanics were less likely to die as a result of breast cancer compared with whites (Asians: HR, 0.56; 95% CI, 0.37 to 0.85; Hispanics: HR, 0.74; 95% CI, 0.58 to 0.95). For blacks, tumor characteristics and stage at diagnosis were significant disparity mediators. Body mass index was an important mediator for blacks and Asians. Conclusion Racial disparities in breast cancer survival vary by tumor subtype. Interventions are needed to reduce disparities, particularly in the first 2 years after diagnosis among black women with estrogen receptor–positive tumors.


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