Molecular drivers of LCIS

JohnSmith
JohnSmith Member Posts: 651
edited June 2016 in ILC (Invasive Lobular Carcinoma)

The University of Pittsburgh is one of the few with strong clinical and research interest in Lobular. They are the first to launch an ILC Clinical Trial to identify markers of endocrine response in ILC, which can be read here and here.

In July 2015, they released research on the "Molecular drivers of lobular carcinoma in situ". While the focus is on LCIS, there's plenty of ILC data to keep some of you interested.
I suggest drinking a strong cup of caffeinated coffee before reading this since it gets a bit technical.

Abstract: Lobular carcinoma in situ (LCIS) is considered to be a risk factor for the development of invasive breast carcinoma, but it may also be a non-obligate precursor to invasive lobular carcinoma (ILC). Many LCIS lesions do not progress to ILC, and the molecular changes that are necessary for progression from LCIS to ILC are poorly understood. Disruption in the E-cadherin complex is the hallmark of lobular lesions, but other signaling molecules, such as PIK3CA and c-src, are consistently altered in LCIS. This review focuses on the molecular drivers of lobular carcinoma, a more complete understanding of which may give perspective on which LCIS lesions progress, and which will not, thus having immense clinical implications.

· Share on FacebookShare on Twitter

Comments

  • JohnSmith
    JohnSmith Member Posts: 651
    edited June 2016

    This is interesting research that fits well into this thread, although probably of more interest to the LCIS crowd.

    It's June 2016 published research about LCIS and ILC sharing a clonal relationship (based on copy number profiling and whole-exome sequencing).

    "Clonal relationships between lobular carcinoma in situ and other breast malignancies"
    Authors: Begg CB1, Ostrovnaya I2, Carniello JV3, Sakr RA3, Giri D4, Towers R3, Schizas M3, De Brot M5, Andrade VP6, Mauguen A2, Seshan VE2, King TA3.

    Abstract
    BACKGROUND: Recent evidence suggests that lobular carcinoma in situ (LCIS) can be a clonal precursor of invasive breast cancers of both the ductal and lobular phenotypes. We sought to confirm these findings with an extensive study of fresh frozen breast specimens from women undergoing mastectomy.

    METHODS: Patients with a history of LCIS presenting for therapeutic mastectomy were identified prospectively. Frozen tissue blocks were collected, screened for lesions of interest, and subjected to microdissection and DNA extraction. Copy number profiling, whole-exome sequencing, or both were performed. Clonal relatedness was assessed using specialized statistical techniques developed for this purpose.

    RESULTS: After exclusions for genotyping failure, a total of 84 lesions from 30 patients were evaluated successfully. Strong evidence of clonal relatedness was observed between an LCIS lesion and the invasive cancer for the preponderance of cases with lobular carcinoma. Anatomically distinct in situ lesions of both ductal and lobular histology were also shown to be frequently clonally related.

    CONCLUSIONS: These data derived from women with LCIS with or without invasive cancer confirm that LCIS is commonly the clonal precursor of invasive lobular carcinoma and that distinct foci of LCIS frequently share a clonal origin, as do foci of LCIS and ductal carcinoma in situ.

    · Share on FacebookShare on Twitter

Categories