Immunoexpression of P63 and SOX2 in triple-negative breast cancers, Indonesia

Abstract

Background: Using immunohistochemical stains to target specific breast cancer markers has become indispensable for evaluation of small diagnostic tissue specimens, and therefore novel marker cocktails for specific breast cancers are required. This study was conducted to assess the immunoexpression of P63 and SOX2 in triple negative breast cancer (TNBC), and to evaluate the predictive diagnostic value of these markers for specific types of TNBC. Methods: Histological slides and paraffin blocks of TNBC cases were collected from Dr. Hasan Sadikin Hospital, Bandung, Indonesia from 5-years period (2011-2015). Each histological slide was subjected to immunohistochemical staining for P63 (nucleus and cytoplasm) and SOX2 (nucleus), with specific primer antibodies. Immunoexpression of P63 and SOX2 was evaluated using immunoreactivity scoring. Associations between P63 and SOX2 immunoexpression and TNBC types were assessed using Mann Whitney tests. In addition, the predictive diagnostic values of these markers were assessed. Results: Forty TNBC histological slides were included, and 23 (57.5%) were Basal-like type TNBC and 17 (42.5%) were Non basal-like type TNBC. Immunoexpression of P63 nucleus and SOX2 was not different between types of TNBC. However, immunoexpression of P63 in the cytoplasm in Basal-like type TNBC was significantly higher than in Non basal-like type TNBC ( p=0.021). Predictor diagnostic value analysis suggested that immunoexpression of P63 in cytoplasm had 56.5% sensitivity and 70.6% specificity for diagnosing Basal-like type TNBC, with area under curve of 0.64. Conclusions: Immunoexpression of P63 in the cytoplasm has a relatively weak diagnostic value to discriminate Basal-like and Non basal-like types of TNBC.

Spatiotemporal Regulation of ΔNp63 by TGFβ-Regulated miRNAs Is Essential for Cancer Metastasis

“…7I and J and Supplementary Table S4). This suggests that the control of ∆Np63 by TGFβ could be more relevant in breast cancers with low levels of ∆Np63 (luminal subtype) than in those with high levels of ∆Np63 (basal subtype) (39)(40)(41)(42). In summary, these data demonstate a negative correlation between TGFβ and ΔNp63 signatures in subtypes of breast and lung tumors, further providing evidence for the regulatory axis of TGFβ/ΔNp63 in human cancers.…”

The TP63 Gene Polymorphism rs17506395 is Associated with Early Breast Cancer in Cameroon

“…Previous studies highlight that the total percentage of p63-positive cells was related to a marked nuclear pleomorphism and that the intensity of p63 staining was associated with a syncytial growth pattern in triple negative breast cancer (Thike et al, 2010). Moreover, higher expression of p63 was reported in the cytoplasm cells of basal-like subtype breast cancer compared to non-basal-like of Indonesian women (Kamarlis et al, 2018). Results obtained in young Cameroonian patients highlighting the high allelic frequency for T allele could be linked to aggressiveness of breast cancer in the young black women because breast cancer in women of below 40 years is more aggressive with a worse clinical outcome compared to older group (Anders et al, 2010;Carvalho et al, 2010;Karihtala et al, 2010).…”

Possible Usage of p63 in Bioptic Diagnostics

“…Nedávno byla popsána nová izoforma GTAp63 vyskytující se u prekurzorů samčích zárodečných buněk, kde přispívá k udržování integrity genomu [9]. Z hlediska onkogeneze je TAp63 obecně považována za nádorový supresor díky schopnosti indukovat zástavu buněčného cyklu a apoptózu [10], zatímco p40 vykazuje vlastnosti onkoproteinu a její vysoká exprese je charakteristická zejména pro dlaždicobuněčné karcinomy [11], uroteliální karcinomy [12] a karcinomy bazálního typu [13][14][15]. O p40 se také diskutuje jako o markeru nádorových kmenových buněk u různých typů nádorových onemocnění [16].…”

“…Nicméně ne všechny neoplastické buňky běžných karcinomů jsou p63 negativní. Mimo jadernou lokalizaci bylo imunohistochemické barvení p63 u řady invazivních BC pozorováno také v cytoplazmě neoplastických buněk, ovšem pouze ve studiích využívajících nejčastěji používanou anti-p63 protilátku klon 4A4 [13,[30][31][32]. Ve srovnání s 4A4 je pak p40 protilátka s výhradně jaderným barvením považována za více specifickou [33].…”

“…Mezi nádory charakteristické vysokou jadernou expresí p63 patří zejména karcinomy bazálního typu 2 (basal like 2 -BL2) patřící do skupiny triple negativních BC (TNBC), které jsou negativní pro estrogenový (ER), progesteronový (PR) receptor a také receptor typu 2 pro lidský epidermální růstový faktor (human epidermal growth factor receptor 2 -HER2) [34]. U TNBC bazálního typu byla pozorována rovněž vyšší exprese p63 v cytoplazmě ve srovnání s nebazálními typy [13]. Jadernou expresi p63 lze nalézt také u malého procenta ER+ karcinomů [35,36].…”