PIK3CA mutation and histological type in breast carcinoma: high frequency of mutations in lobular carcinoma

Abstract

Mutations in the PIK3CA gene have recently been reported in different human neoplasms, including breast cancer. This paper reports the results of a systematic analysis of PIK3CA mutations in different histological types of breast carcinoma. One hundred and eighty invasive breast carcinomas, comprising 74 ductal, 56 lobular, 22 mucinous, 20 medullary, and eight papillary, were selected on the basis of their histological type in a consecutive series of 780 breast cancers. Exons 1-20 of the PIK3CA gene were subjected to SSCP analysis followed by direct sequencing. PIK3CA mutations were observed in 46 (26%) of the 180 tumours examined: 23 (50%) mutations were located in exon 9, and 23 (50%) in exon 20. Mutations were frequent in lobular (46%), less frequent in ductal (22%), and uncommon in medullary (10%), mucinous (5%), and papillary tumours (12%) (p = 0.0002). Mutations in exon 9 were more frequent in lobular carcinomas (30% of cases) than in the other histological types (less than 5% of cases) (p = 0.00014). No significant differences were observed in the distribution of mutations in exon 20. There was no significant correlation between PIK3CA mutations and other clinicopathological and biological variables, including age, tumour size, lymph node metastases, oestrogen receptor (ER) status, progesterone receptor (PgR) status, p53 gene mutations, and p53 protein expression. The findings indicate that in invasive breast carcinomas, PIK3CA alterations are mainly present in lobular and ductal tumours, whereas the other histological types, known to be associated with a favourable prognosis, show a very low incidence of PIK3CA mutations.

PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters

“…31,[36][37][38] For instance, in colorectal carcinomas, their frequency was significantly greater in highgrade and advanced carcinomas (32%) than in lowgrade tumors (3%). 31 Similarly, a higher rate of PIK3CA mutations was found in invasive lobular and ductal breast carcinomas than in other histologic types associated with more favorable prognosis.…”

“…25,27,28 However, in contrast to other epithelial cancers, such as colorectal 31,36 and breast carcinomas, 37,38 no correlation has been found between the distribution of PIK3CA mutations and grade and stage of disease. Given the recently reported role of PIK3CA mutations in tumor invasion and metastases, 29 we analyzed the PIK3CA status in a large series of endometrial adenocarcinomas and compared the results, between PIK3CA-mutated and PIK3CA-nonmutated groups, with the clinicopathological parameters known to be related to prognosis.…”

“…31 Similarly, a higher rate of PIK3CA mutations was found in invasive lobular and ductal breast carcinomas than in other histologic types associated with more favorable prognosis. 37 Also, it has been shown that PIK3CA mutations occur in colorectal adenomas when the neoplastic cells acquire the ability to invade. 31 In a comparative study of 44 endometrioid adenocarcinomas and 29 precursor lesions (complex atypical hyperplasias), PIK3CA mutations were identified in 39% of the former but only 7% of the latter, suggesting that such mutations represent a late event in endometrial carcinogenesis and are associated with invasion.…”

PIK3CA expression in invasive breast cancer: a biomarker of poor prognosis

“…In addition, it has recently been suggested that PIK3CA inhibitor could be used in the treatment of basal-like BC [18]. Contrasting this, some authors have found an association with invasive lobular carcinoma; a type frequently occurring in the luminal-like class of BC [19], and with the resistance to hormonal therapy [20]. Thus, these predominantly small or preclinical studies have yielded a diversity of observations and conclusions.…”

Les cancers du sein

“…D'autres gènes sont altérés par délétion, mutation ou perte d'expression, comme CDH1 (cadhérine E) dans les cancers lobulaires, TP53, et BRCA1 et BRCA2 dans les cancers héréditaires. La sous-unité catalytique P110 de la phosphatidyl-inositol-3 kinase est fréquemment mutée [23]. De nombreuses amplifications et délétions récurrentes ciblant des régions chromosomiques précises ont été identifiées par hybridation génomique comparative.…”