Ki-67, p53 and BCL-2 Expressions and their Association with Clinical Histopathology of Breast Cancer among Women in Tanzania

Mansouri, Hidaya; Mnango, Leah; Magorosa, Erick; Sauli, Elingarami; Mpolya, Emmanuel

doi:10.1038/s41598-019-46184-x

Cited by 23 publications

(22 citation statements)

References 23 publications

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“…Several histological studies have reported the application of most common cellular biomarkers, including Ki-67, cyclin-dependent kinase inhibitor (p16), and ProEx C [topoisomerase II-alpha (TOP2A) and minichromosomal maintenance-2 (MCM2)] in the early diagnosis of cervical cancer [ 14 – 17 ]. Recently, Ki-67 has been demonstrated to be an important cell proliferation biomarker for malignant lesions among women in Tanzania [ 18 , 19 ]. However, several cancer biomarkers, especially when applied individually, may not detect cervical cancer as it develops, making them unsuitable for early diagnosis of cervical cancer [ 16 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania

et al. 2021

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Introduction Biomarkers yield important information for early diagnosis of cervical cancer. However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol’s iodine and Pap test are being used as the standard screening/ diagnostic methods. Methods This was a retrospective hospital-based cross-sectional study that was conducted to assess cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between May 1, 2017 and May 10, 2018. Immunohistochemistry technique was used to detect the expressions of p16 and TOP2A proteins from the retrieved formalin-fixed and paraffin-embedded (FFPE) cervical biopsies. Results A total of 145 patients, with a mean age of 52.1 ± 12.9 years, were included in this study. Upon immunohistochemistry staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive respectively. There was a strong association between histopathological class and p16/TOP2A expression levels (Fisher’s exact test, p<0.001). Moreover, there was a strong positive correlation between p16/TOP2A and cancerous cervical lesions (Spearman’s rank correlation coefficients = 0.833 and 0.687, p = 0.006 and 0.005, respectively). The age-adjusted odds ratio for predicting cervical cancer lesions were independently significant for p16/TOP2A biomarkers in FFPE cervical tissues [p16: OR = 1.142 (95% CI: 1.059–1.232, p<0.001) and TOP2A: OR = 1.046 (95% CI: 1.008–1.085, p = 0.015)]. Importantly, the diagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2% versus 77.6%, accuracy: 92.8% versus 87.8%, respectively). Conclusion Our study has highlighted that over-expression of TOP2A is related to the grade of cervical intraepithelial neoplasia but does not predict prognosis in cervical cancer. Similarly, expression of p16 is related to degree of histological dysplasia and malignancy, suggesting its prognostic and predictive value in the management of cervical cancers. Further bigger studies are needed to validate their applications in the early diagnosis of cervical cancer.

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Section: Introductionmentioning

confidence: 99%

Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania

et al. 2021

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“…e role of apoptosis in physiology cannot be overemphasized as it checks the activities of mitosis and cell proliferation in the regulation of cell populations. ese biomarkers (Ki-67, bcl-2 (protein), and p53) have been studied in prostate, melanomas, and other cancers in the general population [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

The Analysis of bcl-2 in Association with p53 and Ki-67 in Triple Negative Breast Cancer and Other Molecular Subtypes in Ghana

Ameh-Mensah

Duduyemi

Bedu-Addo

et al. 2021

Journal of Oncology

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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.

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“…Ki67 is a protein encoded by the Ki67 gene and is closely associated with cell proliferation. Some studies have found that it can predict the prognosis of breast cancer patients with bone metastasis (16). However, the value of Ki67 as an indicator of the therapeutic response to adjuvant treatment in patients with soft-tissue sarcomas has been questioned (17).…”

Section: Immunohistochemical Analysismentioning

confidence: 99%

Analysis of prognostic factors in 171 patients with myxofibrosarcoma of the trunk and extremities: a cohort study

Liu

Zhang

et al. 2021

Ann Transl Med

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Background: Myxofibrosarcoma (MFS) of the trunk and extremities has unique clinical features. However, it is not clear which indicators are the influencing factors of recurrence, metastasis, and survival of trunk and limb MFS. The aim of the present study was to analyze clinical features and prognosis of trunk and limb MFS.Methods: The data of 171 patients with MFS of the trunk and extremities and a median follow-up period of 67 months from January 1999 to July 2018 were retrospectively analyzed. Risk factors for survival, recurrence and metastasis following resection of MFS of trunk and extremities were analyzed. The Kaplan-Meier method (log-rank test) was used for the univariate analysis and a Cox regression model was used for the multivariate analysis. Results:The median age of the patients was 53 years; there were 111 males and 60 females. A total of 132 cases had French Federation of Cancer Centers grade 1, 24 cases had grade 2, and 15 cases had grade 3 MFS. The 3-year recurrence, 3-year metastasis, and 5-year survival rates were 29.2%, 19.3%, and 93.6%, respectively. Kaplan-Meier survival analysis showed that the surgical margin (χ 2 =22.228, P<0.001) and tumor size (χ 2 =6.697, P=0.010) were associated with recurrence. The surgical margin (χ 2 =12.353, P<0.001) and CD44 expression (χ 2 =5.227, P=0.022) were associated with metastasis. The multivariate analysis showed that the surgical margin [hazard ratio (HR) =3.635, 95% confidence interval (CI): 1.883-7.016, P<0.001] and tumor size (HR =1.889, 95% CI: 1.039-3.435, P=0.037) were risk factors for local recurrence. In addition, the surgical margin (HR =4.475, 95% CI: 1.918-10.438, P=0.001) and presence of CD44 (HR =3.406, 95% CI: 1.462-8.405, P=0.005) were risk factors for distant metastasis.Conclusions: A negative surgical margin can be reduced effectively the rate of recurrence and metastasis in patients with MFS of the trunk and limbs. In addition, CD44 may be used to assess the metastatic risk of patients with MFS.

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Ki-67, p53 and BCL-2 Expressions and their Association with Clinical Histopathology of Breast Cancer among Women in Tanzania

Cited by 23 publications

References 23 publications

Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania

Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania

The Analysis of bcl-2 in Association with p53 and Ki-67 in Triple Negative Breast Cancer and Other Molecular Subtypes in Ghana

Analysis of prognostic factors in 171 patients with myxofibrosarcoma of the trunk and extremities: a cohort study

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