Combined Immunohistochemistry of PLK1, p21, and p53 for Predicting TP53 Status. (August 2015)

• Record Type: Journal Article
• Authors: Watanabe, Gou; Ishida, Takanori; Furuta, Akihiko; Takahashi, Shin; Watanabe, Mika; Nakata, Hideaki; Kato, Shunsuke; Ishioka, Chikashi; Ohuchi, Noriaki
• Is Part Of: American journal of surgical pathology. Volume 39:Number 8(2015)
• Publication Date: 2015-08
• Subjects: Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000000386
• Languages: English
• ISSNs: 0147-5185

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>It is difficult to predict the <italic>TP53</italic> status by p53 immunohistochemistry (IHC). We aimed to improve the accuracy of p53 IHC with p53-regulated proteins for predicting the <italic>TP53</italic> mutation status. <italic>TP53</italic> mutations were detected in 19 of 38 breast cancer patients (50%). Five of 7 cases of protein-truncating mutation of <italic>TP53</italic> were completely negative for p53 IHC, whereas 11 of 12 cases of <italic>TP53</italic> point mutation were strongly positive for p53 IHC. Therefore, to avoid false negatives, we extracted p53-dependent universally downregulated genes using microarray analysis from 38 breast cancer patients and 2 p53-inducible cell lines. From 9 commonly repressed genes, we evaluated 3 genes, <italic>baculoviral IAP repeat-containing 5</italic> (<italic>BIRC5</italic>)<italic>, polo-like kinase 1</italic> (<italic>PLK1</italic>), and <italic>BUB1 mitotic checkpoint serine/threonine kinase</italic> (<italic>BUB1</italic>), which were previously identified as p53-dependent repressed genes. PLK1≥Allred total score (TS) 5 showed the highest correlation with <italic>TP53</italic> mutation. To decrease false positivity, we evaluated p21 IHC. Although strong staining of p21 was observed in 4 cases (10.5%), all 4 were wild-type <italic>TP53</italic>. Thus, p53 mutation-like (p53mt-like) IHC was identified by p53 TS7, 8 with PLK1≥TS 5 and p21 TS⩽6. p53 mt-like IHC correlated with <italic>TP53</italic> mutation (predictive value=0.94). In other 157 breast cancer cases, p53 mt-like was an independent prognostic marker in multivariate analysis and a strong prognostic factor. Stratification with p53 mt-like IHC identified patients with a poorer prognosis. In conclusion, we identified reliable IHC conditions to predict the <italic>TP53</italic> status of breast cancer patients.</p> </sec> </abstract>