Pleomorphic lobular carcinoma of the breast: role of comprehensive molecular pathology in characterization of an entity

Abstract

Immunohistochemical analysis of E-cadherin has changed the way lobular neoplasia is perceived. It has helped to classify difficult cases of carcinoma in situ with indeterminate features and led to the identification of new variants of lobular carcinoma. Pleomorphic lobular carcinoma (PLC) and pleomorphic lobular carcinoma in situ (PLCIS), recently described variants of invasive and in situ classic lobular carcinoma, are reported to be associated with more aggressive clinical behaviour. Although PLC/PLCIS show morphological features of classic lobular neoplasia and lack E-cadherin expression, it is still unclear whether these lesions evolve through the same genetic pathway as lobular carcinomas or are high-grade ductal neoplasms that have lost E-cadherin. Here we have analysed a case of extensive PLCIS and invasive PLC associated with areas of E-cadherin-negative carcinoma in situ with indeterminate features, using immunohistochemistry, chromogenic in situ hybridization, high-resolution comparative genomic hybridization (CGH) and array-based CGH. We observed that all lesions lacked E-cadherin and beta-catenin and showed gain of 1q and loss of 16q, features that are typical of lobular carcinomas but are not seen in high-grade ductal lesions. In addition, amplifications of c-myc and HER2 were detected in the pleomorphic components, which may account for the high-grade features in this case and the reported aggressive clinical behaviour of these lesions. Taken together, these data suggest that at least some PLCs may evolve from the same precursor or through the same genetic pathway as classic lobular carcinomas.

A high-resolution integrated analysis of genetic and expression profiles of breast cancer cell lines

“…Microarray-based comparative genomic hybridisation (aCGH) and cDNA microarray hybridisations For array CGH, 1 lg DNA from each cell line was labelled with either Cy3 or Cy5 using a modified BioPrime labelling reaction (InVitrogen) [15,16]. Labelling, hybridisations and washes were performed as previously described [17,18].…”

Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy

“…Estimated purity of tumour cells ranged from 75 to 100% (median ¼ 90%) (Supplementary Figure 1). DNA was extracted according to standard methods (Reis-Filho et al, 2005b). The DNA yield and purity was assessed by spectrophotometry and the DNA quality (DNA fragment size range) by agarose gel electrophoresis as described previously (Reis-Filho et al, 2005b).…”

Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma

“…In comparison with non-ILC, ILC is significantly more likely to occur in older patients, to be of larger size, hormone-receptor positive, of intermediate grade and without vascular invasion [3,4]. Pleomorphic lobular carcinomas of the breast display histological features associated with ILC, yet they also exhibit more nuclear atypia and pleomorphism, and an aggressive clinical behaviour [5][6][7].…”