Impact of SOX18 expression in cancer cells and vessels on the outcome of invasive ductal breast carcinoma.
OBJECTIVE
SOX18 is a transcription factor known to be involved in hair follicle, blood and lymphatic vessel development, as well as wound healing processes (together with SOX7 and SOX17). In addition, it has been reported that SOX18 may affect the growth of cancer cells in vitro. Until now, the exact role of SOX18 expression in invasive ductal breast carcinoma (IDC) has remained unknown.


METHODS
In this study, we have investigated SOX18 expression in cancer cells and endothelial cells in 122 IDC samples using immunohistochemistry (IHC). SOX18 expression was also determined using real-time PCR and Western blotting in a series of breast cancer-derived cell lines (i.e., MCF-7, BT-474, SK-BR-3, MDA-MB-231, BO2).


RESULTS
Using IHC, we observed SOX18 nuclear expression in cancer cells, as well as in blood and lymphatic vessels of the IDC samples tested. SOX18 expression in the IDC samples correlated with a higher malignancy grade (Grade 2 and Grade 3 versus Grade 1; p = 0.02 and p = 0.009, respectively) and VEGF-D expression (r = 0.27, p = 0.007). SOX18 expression was also associated with HER2 positivity (p = 0.02). A significantly higher SOX18 expression was found in the HER2-positive cell line BT-474, and a significantly lower expression in the triple negative cell lines MDA-MB-231 and BO2. Laser capture microdissection of IDC samples revealed significantly higher mRNA SOX7, SOX17 and SOX18 expression levels in the vessels as compared to the cancer cells (p = 0.02 and p = 0.0002, p < 0.0001, respectively). SOX18 positive intratumoral and peritumoral microvessel counts (MVC) were associated with higher malignancy grades (p = 0.04 and p = 0.02, respectively). Moreover, peritumoral SOX18 positive MVC were found to act as an independent marker for a poor prognosis (p = 0.04).


CONCLUSIONS
SOX18 expression may serve as a marker for a poor prognosis in IDC.
Regional Specialist Hospital, Research and Development Center, Wroclaw, Poland.
Bartosz
B
Pula
Mateusz
M
Olbromski
Andrzej
A
Wojnar
Agnieszka
A
Gomulkiewicz
Wojciech
W
Witkiewicz
Maciej
M
Ugorski
Piotr
P
Dziegiel
Marzena
M
Podhorska-Okolow
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D042601:Lymphatic Vessels / Q000378:metabolism; D061986:MCF-7 Cells; D055806:Microvessels / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055760:SOXF Transcription Factors / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics / Q000378:metabolism
D018719:Erb-b2 Receptor Tyrosine Kinases; D055760:SOXF Transcription Factors; D042643:Vascular Endothelial Growth Factor D; C109188:SOX17 protein, human; C095473:SOX18 protein, human; C484456:SOX7 protein, human