PIK3CA, KI67, Estrogen (ER) and Progesterone Receptors (PR) Expression Pattern of in HER2 Positive Breast Cancers

Abstract

Background: PIK3CA mutations have been reported to be associated with resistance to therapy in HER2+ breast cancers. This study, therefore, became imperative to determine the expression pattern of this mutant protein together with ER, PR and KI67 in order to serve as a useful predictive tool in the management of HER2 breast cancers.Methods: A total of 53 archived formalin-fixed, paraffin-embedded HER2+ breast cancer tissue blocks from 2015 to 2019 were used for the study in NAUTH Nnewi. The selected blocks were sectioned and stained with haematoxylin and eosin staining techniques. HER2, ER and PR status confirmation as well as PIK3CA and KI67 protein expressions were evaluated using immunohistochemistry (Avidin-biotin complex method). PIK3CA and KI67 expressions in the tissue were scored based on proportion and intensity of immune-labelling using the semi-quantitative method.Result: The mean age of subjects was 47 years and the breast cancers were all invasive ductal carcinoma. Twenty-nine (54.7%) were ER+ while 24 (45.3%) were ER-. Twenty-one (39.6%) were PR+ while 32 (60.4%) were PR-. Twenty-one (39.6%) were PIK3CA negative, 9(35.8%) showed low PIK3CA, while 13(24.5%) showed high PIK3CA. Thirty-four (64.2%) were negative for KI67, 11(20.8%) showed low KI67, while 8(15.5%) showed high KI67. There was weak and moderate positive relationship between ER/PR status and PIK3CA (r=-0.032; p=0.822) and KI67 (r=0.050; p=0.721) respectively. A weak negative correlation between KI67 and PIK3CA (r=-0.118; p=0.401) were observed with 12 (22.4%) of the 13 highly positive PIK3CA cases showing either negative or low for KI67 immunoreactivity while 7(13.2%) of the 8 highly positive KI67 cases showed either negative or low PIK3CA immunoreactivity.Conclusion: This study established a moderate expression of PIK3CA mutant protein. It also pointed out an existing interesting relationship between PIK3CA and KI67, which can be further revealed in future studies.

Next-Generation Sequencing-Based Analysis of Clinical and Pathological Features of PIK3CA-Mutated Breast Cancer

“…The expression of PR was significantly elevated in PIK3CA -M patients, which aligns with earlier findings [ 41 , 42 ]. The earliest reports linking PIK3CA alterations with higher expression of progesterone receptors date back to 2006, when Saal et al investigated the relations between PIK3CA , PTEN loss, and hormone receptor status [ 43 ].…”

“…Specifically, median expression stood at 17.5% in mutated samples, compared to 25% in wild-type samples. This implies a potentially less aggressive biology of the tumor, a conclusion that harmonizes with previous findings in the literature [ 41 , 51 , 52 ]. While both the heightened expression of PR and lower levels of Ki67 in PIK3CA -M tumors are described in the literature, the molecular background of this occurrence remains unexplained.…”

Diagnosis of breast cancer lesion using ultrasound images, elastography, and Ki-67 protein cell proliferation index

“…A previous study showed that average percentage of positivity of the cell proliferation index (Ki-67 protein) is related to the condition before and after menopause. Hence, breast cancer in young women before menopause often has a higher cell proliferation index (8). In the present study, the relationship between cell proliferation index (Ki-67 protein) and menopause status was significant.…”

“…Ultrasound devices are widely available and have a more reasonable price than other devices (6,7). Compared to other medical imaging techniques, they are safe, fast, noninvasive, painless, and relatively cheap (8).…”

Evaluating the correlation of Hedgehog pathway with Claudin-1 expression in invasive breast cancer

“…Epithelial to mesenchymal transition (EMT) is a phenotypic change related to the process of metastasis and is considered a risk factor for breast cancer. During EMT, an expression change from E-cadherin (epithelial marker) to N-cadherin (mesenchymal marker) is seen, and this event causes a change in extracellular matrix adhesion (12).…”