Mutant Phenotype p53 Immunohistochemical Expression Is Associated With Poor Prognostic Parameters and Disease-Free Survival in Triple-Negative Metaplastic Breast Carcinoma

Abstract

IntroductionMetaplastic breast carcinoma (MBC) is a special type of breast cancer that is most commonly triple-negative and has the worst outcome compared to other breast tumors. p53 is a tumor suppressor gene that is frequently mutated in many human cancers. The association of mutant p53 immunohistochemical expression with clinical and prognostic parameters has not been widely studied in triple-negative MBC. Therefore, in this study, we evaluated the expression patterns of p53 in triple-negative MBC and its association with clinical and prognostic parameters. MethodsA retrospective observational study was conducted in the Department of Histopathology at Liaquat National Hospital and Medical College, Pakistan, for a duration of 11 years. A total of 101 cases of triple-negative MBCs were included in the study. p53 immunohistochemistry was performed on the representative tissue blocks. Cases with diffuse strong positive p53 expression were labeled mutant phenotype, while cases with weak patchy p53 expression were termed wild-type. ResultsThe mean age of the patients was 48.33±11.47 years, and the mean tumor size was 3.98±2.07 cm. The mean Ki67 index was 48.98±22.97%. The median disease-free survival of the patients was 24 (three to 68) months, with a median follow-up of 37 (13 to 77) months. Most of the cases were tumor (T)-stage II (51.5%). Axillary metastasis was present in 36.6% of cases, with the perinodal extension in 16.8% of cases. Most cases were non-basal subtype (91.1%), and the majority of cases were grade III (85.1%). Recurrence was observed in 17.8% of cases. Among 101 cases, 52.5% cases showed mutant phenotype p53 expression. A significant association of p53 expression was noted with tumor grade, Ki67 index and disease-free survival. Cases with mutant phenotype p53 expression had a higher tumor grade, higher Ki67 index, and poorer disease-free survival than cases with wild-type p53 expression. ConclusionA substantial proportion of triple-negative MBC expressed diffuse strong expression (mutant phenotype) of p53 in our study, signifying a potential role of p53 as a therapeutic target in triple-negative MBC. Moreover, association of p53 with poor prognostic parameters, such as higher tumor grade and Ki67, and poor diseasefree survival underscores the prognostic significance of p53 in triple-negative MBC.

Clinicopathological Parameters and Biomarker Profile in a Cohort of Patients With Head and Neck Squamous Cell Carcinoma (HNSCC)

“…Mutations in these genes lead to the formation of truncated proteins that are resistant to protease digestion and are therefore abnormally expressed. Conversely, sometimes null mutations of p53 also lead to a complete absence of p53 protein, as detected by immunohistochemical (IHC) analysis [6][7][8]. The high expression of p16 is also associated with HPV infection [9][10].…”