Abstract
PLEKHA7 is a junctional protein, which participates in a complex that stabilizes E-cadherin at the zonula adhaerens. Since E-cadherin is involved in epithelial morphogenesis, signaling, and tumor progression, we explored PLEKHA7 expression in cancer. PLEKHA7 expression was assessed in invasive ductal and lobular carcinomas of the breast by immunohistochemistry, immunofluorescence and quantitative RT-PCR. PLEKHA7 was detected at epithelial junctions of normal mammary ducts and lobules, and of tubular and micropapillary structures within G1 and G2 ductal carcinomas. At these junctions, the localization of PLEKHA7 was along the circumferential belt (zonula adhaerens), and only partially overlapping with that of E-cadherin, p120ctn and ZO-1, as shown previously in rodent tissues. PLEKHA7 immunolabeling was strongly decreased in G3 ductal carcinomas and undetectable in lobular carcinomas. PLEKHA7 mRNA was detected in both ductal and lobular carcinomas, with no observed correlation between mRNA levels and tumor type or grade. In summary, PLEKHA7 is a junctional marker of epithelial cells within tubular structures both in normal breast tissue and ductal carcinomas, and since PLEKHA7 protein but not mRNA expression is strongly decreased or lost in high grade ductal carcinomas and in lobular carcinomas, loss of PLEKHA7 is a newly characterized feature of these carcinomas.
Highlights
Breast carcinoma is the most common cancer in women both in the developed and non-developed world, and the second leading cause of cancer death in women, after lung cancer
Formalin fixed paraffin embedded (FFPE) and frozen tissue samples of normal and breast carcinoma tissues were obtained from the archives of the Division of Clinical Pathology at the Geneva University Hospital, according to a protocol approved by the Geneva Cantonal Committee for Research Ethics (CCER) (Protocol number 14–272, Project title “Expression of junctional proteins in breast cancer”), and which has no requirement for written informed consent, because it is a retrospective study
To validate the specificity of this antibody for human tissues, we examined its reactivity using cultured human epithelial cells depleted of PLEKHA7 through siRNA expression
Summary
Breast carcinoma is the most common cancer in women both in the developed and non-developed world, and the second leading cause of cancer death in women, after lung cancer. Breast carcinomas are classified into invasive and non-invasive, based on their infiltrating characteristics, and comprise a range of tumor types, among which ductal carcinomas are the most common, and lobular carcinomas represent about 5–10% of the total. Distinctive morphology and PLOS ONE | DOI:10.1371/journal.pone.0135442. Distinctive morphology and PLOS ONE | DOI:10.1371/journal.pone.0135442 August 13, 2015
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
