Matrix-producing Breast Carcinoma: A Rare Subtype of Metaplastic Breast Carcinoma

Matrix-producing carcinoma (MPC) is a rare subtype of metaplastic breast carcinoma (MBC) that was first described in 1989 by Wargotz and Norris. It accounts for less than 1% of breast carcinomas and has distinctive clinical, morphological, and immunohistochemical features. Histologically it consists of invasive carcinoma of no special type with transition to cartilaginous or osseous matrix without a spindle cell component. Data on this entity are limited with the literature consisting mostly of case reports and a small number of case series. We report a case of matrix-producing breast carcinoma, with excellent clinical outcome. We also discuss the histogenesis, imaging, histological, and immunohistochemical characteristics, treatment, and focus on the differential diagnosis of this rare tumor

Human kallikrein-related peptidase 12 (KLK12) splice variants expression in breast cancer and their clinical impact

Kallikrein-related peptidases (KLKs) are a group of 15 serine proteases, hormonally regulated, and localized on chromosome 19q13.4. Alternative splicing is a process that plays significant role in the development, physiology, and different diseases, like cancer. Kallikrein family numbers more than 82 alternative transcripts. Understanding the role that those gene transcripts play in various cancer types, could lead to the discovery of diagnostic markers or drug targets. The present study was designed to analyze the expression profile of the splice variants of kallikrein-related peptidase 12 (KLK12) in breast cancer patients and to evaluate their clinical significance. KLK12 splice variants (KLK12sv3 and KLK12sv1/KLK12sv2) were examined in 69 tissue samples of breast cancer using quantitative real-time PCR as well as semi-quantitative PCR. Relative quantitative expression of KLK12 was statistically associated to clinicopathological parameters. From the splice variants examined, statistical associations with clinicopathological parameters were obtained only from KLK12sv3 variant. KLK12sv3 is more frequently expressed in tumors of lower grade (p = 0.040), early patient TNM stage (p = 0.024), and smaller tumor size (p = 0.023). Positive KLK12sv3 expression is associated with longer patient disease-free survival (DFS) (p = 0.042) and higher progesterone receptor concentration (p = 0.008). KLK12sv1/KLK12sv2 expression is statistically associated with KLK12sv3 expression (p = 0.001). KLK12sv3 can be regarded as a marker of good prognosis in breast cancer

Abstract LB-72: Expression of the <i>BCL2-like 12</i> (<i>BCL2L12</i>) gene is associated with prolonged survival of breast adenocarcinoma patients.

Abstract The objective of this study was to evaluate the prognostic value of the BCL2-like 12 (BCL2L12) splice variants in breast adenocarcinoma. BCL2L12 is a member of the BCL2 family, aberrantly expressed in several human malignancies, including gastrointestinal cancer, head and neck squamous cell carcinoma, nasopharyngeal carcinoma, and chronic lymphocytic leukemia. We have recently cloned ten novel alternatively spliced variants of this apoptosis-related gene, predicted to encode multiple protein isoforms with distinct functions. Up to date, only the classical isoform has been studied. This one was shown to inhibit apoptosis by neutralizing Caspase-3 and Caspase-7 as well as p53 signaling in glioblastoma. Total RNA was isolated from 140 primary breast tumors and adjacent non-cancerous breast tissue specimens, as well as from breast cancer cell lines. After testing the RNA quality, cDNA was prepared by reverse transcription. A common forward primer and a variant-specific reverse primer were designed and used for the PCR-based expression analysis of each distinct BCL2L12 splice variant. A highly specific and sensitive real-time PCR method was also developed for the quantification of the BCL2L12 main transcript (detection limit: 10 mRNA copies / μL), followed by extensive biostatistical analysis. Calculations were made with the comparative CT (2−▵▵CT) method, using HPRT1 as endogenous control gene and the MCF-7 cell line as calibrator. BCL2L12 splice variants 1, 2, 4, 5, 10, 11, 12, and 13 were detected in breast cancer cells. Among all these mRNA isoforms, the main transcript (BCL2L12 v.1) presented the greatest alterations. This variant was significantly lower in breast adenocarcinomas than in their normal counterparts. Moreover, its expression was inversely associated with estrogen receptor (ER) status (P=0.031), tumor size (P=0.032), TNM stage (P=0.021), and presence of distant metastases (P&amp;lt;0.001). Kaplan-Meier survival analysis and univariate Cox regression indicated that BCL2L12 v.1 is a significant prognosticator of prolonged disease-free and overall survival (P&amp;lt;0.001 in both cases). Most importantly, according to the developed multivariate Cox regression models, the favorable prognostic value of BCL2L12 mRNA expression regarding disease-free survival is independent of the tumor grade, TNM stage, and patients' age (P=0.047). Our findings suggest that the expression of the main transcript (BCL2L12 splice variant 1) of the apoptosis-related BCL2L12 gene merits further investigation as a novel, candidate molecular biomarker predicting prolonged disease-free and overall survival in breast adenocarcinoma patients. Acknowledgements: This work was supported by a THALIS grant (#224), co-funded by the European Union (European Social Fund) and National Resources (NSRF 2007-2013, Operational Programme “Education and Lifelong Learning”). Citation Format: Athina Kladi-Skandali, Christos K. Kontos, Alexandros Tzovaras, Maroulio Talieri, Ioannis Missitzis, Alexandros Ardavanis, Andreas Scorilas. Expression of the BCL2-like 12 (BCL2L12) gene is associated with prolonged survival of breast adenocarcinoma patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-72. doi:10.1158/1538-7445.AM2013-LB-72</jats:p