Neurotensin Receptor 1 (NTSR1) Overexpression in Breast Carcinomas Is Common and Independent of ER/PR/Her2 Expression

Abstract

<p class="MsoNormal"> <span lang="EN-US">Neurotensin (NT) is a 13-amino acid peptide with trophic effects on some neoplasms. Its bioactivities are mainly medi</span><span lang="EN-US">ated by neurotensin receptor 1 (NTSR1). Both NT and NTSR1 were found to be upregulated in breast cancer. NT/NTSR1 thus becomes a potential therapeutic target. We studied whether any correlation exists between the expres</span><span lang="EN-US">sion of NTSR1 in breast carcinomas and the expression of ER, PR, and Her2. A total 85 cases of invasive ductal (62) and lobular (23) breast carcinomas were studied. Based on their ER/PR profiles, the ductal carcinomas (DCs) were subcategorized into ER+/PR+ (21), ER+/PR<span style="white-space:nowrap;">﹣</span> (20), and ER<span style="white-space:nowrap;">﹣</span>/PR<span style="white-space:nowrap;">﹣</span> (21). All of the lobular carcinomas (LCs) were ER+/PR+. 21.57% of all DCs and 5.56% of LCs were Her2 positive. 77.78% of ER<span style="white-space:nowrap;">﹣</span>/PR<span style="white-space:nowrap;">﹣</span> DCs were also Her2 negative (triple negative). The expression of NTSR1 was detected by immunohistochemistry and was semiquantitated (as nega</span><span lang="EN-US">tive, 1+, 2+, 3+). Both 2+ and 3+ were collectively defined as overexpression. The expression of NTSR1 was weak and focal in non-neoplastic mammary epithelial cells. It is increased in 74.19% of DCs (80.95% in ER+/PR+, 75% in ER+/PR<span style="white-space:nowrap;">﹣</span>, and 66.67% in ER<span style="white-space:nowrap;">﹣</span>/PR<span style="white-space:nowrap;">﹣</span> group), and in 95.65% of LCs. The overexpression of NTSR1 is similar between ER+ DCs and ER<span style="white-space:nowrap;">﹣</span> DCs (75% vs 66.67%, p > 0.05) as well as between PR+ DCs and PR<span style="white-space:nowrap;">﹣</span> DCs (80.95% in ER+/PR+ DCs vs 75% in ER+/PR<span style="white-space:nowrap;">﹣</span> DCs, p > 0.05). And it was seen in 77.78% of Her2+ DCs, 78.38% of Her2<span style="white-space:nowrap;">﹣</span> DCs, 94.12% of Her2<span style="white-space:nowrap;">﹣</span> LCs, and 78.57% of triple negative DCs. Overall, NTSR1 is commonly overexpressed in both ductal and lobular breast carcinomas and is independent of the ER/PR/Her2 profiles of the tumors. The present data supports the potential benefit of developing NTSR1 blockers in the adjuvant therapy of breast carcinomas, particularly for those </span><span lang="EN-US">“</span><span lang="EN-US">triple nega</span><span lang="EN-US">tive</span><span lang="EN-US">”</span><span lang="EN-US"> tumors.</span><span lang="EN-US"><!--?xml:namespace prefix = o /--><o:p></o:p></span> </p

Proof of Therapeutic Efficacy of a 177Lu-Labeled Neurotensin Receptor 1 Antagonist in a Colon Carcinoma Xenograft Model

“…In colon carcinoma, breast cancer, and pancreatic adenocarcinoma, NTR1 expression has been associated with neoplastic progression (5)(6)(7)(8). Furthermore, autoradiographic studies have shown that NTR1 is expressed in pancreatic adenocarcinoma in high densities of 10 3 -10 4 dpm/mg in primary tumors (9) and metastases (8).…”