Florid lobular carcinoma in situ: molecular profiling and comparison to classic lobular carcinoma in situ and pleomorphic lobular carcinoma in situ

Shin, Sandra J.; Lal, Aseem; Vries, S. De; Suzuki, Junko; Roy, Ritu; Hwang, E. Shelley; Schnitt, Stuart J.; Waldman, Frederic M.; Chen, Yunn-Yi

doi:10.1016/j.humpath.2013.04.004

Cited by 55 publications

(42 citation statements)

References 24 publications

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“…Two large studies of DCIS (approximately 400 patients) have reported amplification of CCND1 in 10–12.6% of patients with pure DCIS and 14.8–17.4% of patients with DCIS associated with invasive breast cancer, with the majority of patients having amplification in the paired invasive component [39, 40]. In a much smaller series of 20 patients with florid LCIS (a subtype putatively more likely to associated with invasive disease) 25% had CCND1 amplification [41]. This, together with the finding that CCND1 amplification is usually homogeneous within breast carcinomas, suggests that it is an early event in the development of some breast cancers [42].…”

Section: Discussionmentioning

confidence: 99%

PIK3CA mutations are common in lobular carcinoma in situ, but are not a biomarker of progression

et al. 2017

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BackgroundLobular carcinoma in situ (LCIS) is a non-invasive breast lesion that is typically found incidentally on biopsy and is often associated with invasive lobular carcinoma (ILC). LCIS is considered by some to be a risk factor for future breast cancer rather than a true precursor lesion. The aim of this study was to identify genetic changes that could be used as biomarkers of progression of LCIS to invasive disease using cases of pure LCIS and comparing their genetic profiles to LCIS which presented contemporaneously with associated ILC, on the hypothesis that the latter represents LCIS that has already progressed.MethodsSomatic copy number aberrations (SCNAs) were assessed by SNP array in three subgroups: pure LCIS, LCIS associated with ILC and the paired ILC. In addition exome sequencing was performed on seven fresh frozen samples of LCIS associated with ILC, to identify recurrent somatic mutations.ResultsThe copy number profiles of pure LCIS and LCIS associated with ILC were almost identical. However, four SCNAs were more frequent in ILC than LCIS associated with ILC, including gain/amplification of CCND1. CCND1 protein over-expression assessed by immunohistochemical analysis in a second set of samples from 32 patients with pure LCIS and long-term follow up, was associated with invasive recurrence (P = 0.02, Fisher’s exact test). Exome sequencing revealed that PIK3CA mutations were as frequent as CDH1 mutations in LCIS, but were not a useful biomarker of LCIS progression as they were as frequent in pure LCIS as in LCIS associated with ILC. We also observed heterogeneity of PIK3CA mutations and evidence of sub-clonal populations in LCIS irrespective of whether they were associated with ILC.ConclusionsOur data shows that pure LCIS and LCIS co-existing with ILC have very similar SCNA profiles, supporting the hypothesis that LCIS is a true precursor lesion. We have provided evidence that over-expression of CCND1 may identify a subgroup of patients with pure LCIS who are more likely to develop invasive disease, in contrast to PIK3CA mutations, which occur too early in lobular tumorigenesis to be informative.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0789-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

PIK3CA mutations are common in lobular carcinoma in situ, but are not a biomarker of progression

et al. 2017

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“…In Situ Lobular Lesions.-Two variants of lobular carcinoma in situ (LCIS)-pleomorphic lobular carcinoma in situ ( Figure 3, A and B) 12 and florid LCIS with central necrosis (Figure 3, C and D) 13 -can mimic high-grade DCIS and low-grade DCIS with central necrosis, respectively. Loss of E-cadherin in IHC analysis is critical for differentiating the 2 variants of LCIS and DCIS.…”

Section: Distinguishing Between Lobular and Ductal Lesionsmentioning

confidence: 99%

Update on Immunohistochemical Analysis in Breast Lesions

Peng¹,

Butt²,

Chen³

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

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Context.-The utility of immunohistochemistry (IHC) in breast lesions needs to be updated with exceptions among these lesions. Biomarker studies with IHC in triple-negative breast carcinoma may help develop targeted therapies for this aggressive breast cancer. The distinction of metastatic lung adenocarcinoma to the breast and invasive breast carcinoma has significant prognostic and therapeutic implications. The determination can be challenging because both primary tumors can express estrogen receptor and/or HER2 by IHC, creating a diagnostic dilemma.Objectives.-To provide a practical update on the use of IHC markers in differential diagnoses in breast lesions, including benign, atypical, precancerous, and malignant tumors; to highlight recently published research findings on novel IHC markers in triple-negative breast carcinoma cases; and to reinforce the importance of IHC use as an ancillary tool in distinguishing metastatic lung adenocarcinoma to the breast from primary breast carcinoma using real case examples.Data Sources.-PubMed (US National Library of Medicine, Bethesda, Maryland) literature review and authors' research data and personal experiences were used in this review.Conclusions.-Immunohistochemistry has an important role in making differential diagnoses in breast lesions in morphologically equivocal settings; recognizing IHC expression status in the exceptions among these lesions will aid in the correct diagnosis of challenging breast cases. Studies suggest that androgen receptor, p16, p53, GATA3, and PELP1 may have potential diagnostic, prognostic, and predictive value in triple-negative breast carcinoma cases; these findings may provide insight and a greater understanding of the tumor biology in triple-negative breast carcinomas. In distinguishing metastatic estrogen receptor-positive or HER2 þ lung adenocarcinoma to the breast from primary breast carcinoma, napsin A, TTF-1, and GATA3 comprise a useful IHC panel.

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“…The dis tinction of pLCIS from classical LN relies on nuclear charac teristics, with pLCIS having larger, more pleomorphic nuclei with obvious nucleoli and potentially showing apocrine differ entiation, necrosis, and microcalcifications. fLCIS is another form of LIN with high risk, which may be frequently associ ated with microinvasion [39,40]. In the grading system of LIN (LIN 1-3), pLCIS and fLCIS are categorized as the most severe grade (LIN 3) [41].…”

Section: Prognostic and Predictive Factorsmentioning

confidence: 99%

AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2016

2016

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Florid lobular carcinoma in situ: molecular profiling and comparison to classic lobular carcinoma in situ and pleomorphic lobular carcinoma in situ

Cited by 55 publications

References 24 publications

PIK3CA mutations are common in lobular carcinoma in situ, but are not a biomarker of progression

PIK3CA mutations are common in lobular carcinoma in situ, but are not a biomarker of progression

Update on Immunohistochemical Analysis in Breast Lesions

AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2016

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