Abstract
Neurotensin (NT) is a 13-amino acid peptide with trophic effects on some neoplasms. Its bioactivities are mainly mediated 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 expression 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﹣ (20), and ER﹣/PR﹣ (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﹣/PR﹣ DCs were also Her2 negative (triple negative). The expression of NTSR1 was detected by immunohistochemistry and was semiquantitated (as negative, 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﹣, and 66.67% in ER﹣/PR﹣ group), and in 95.65% of LCs. The overexpression of NTSR1 is similar between ER+ DCs and ER﹣ DCs (75% vs 66.67%, p > 0.05) as well as between PR+ DCs and PR﹣ DCs (80.95% in ER+/PR+ DCs vs 75% in ER+/PR﹣ DCs, p > 0.05). And it was seen in 77.78% of Her2+ DCs, 78.38% of Her2﹣ DCs, 94.12% of Her2﹣ 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 “triple negative” tumors.
Highlights
Neurotensin (NT) is a 13-amino acid regulatory peptide that was initially isolated from bovine hypothalamus by Carraway and Leeman [1] and was subsequently found to express highest in the small intestine [2]
We studied whether any correlation exists between the expression of neurotensin receptor 1 (NTSR1) in breast carcinomas and the expression of estrogen receptor (ER), progesterone receptor (PR), and Her2
It has been found in breast carcinomas that near all breast ductal carcinomas over express NTSR1 and about a third coexpress both NT and NTSR1 [5], NT exerted an inhibitory activity on the apoptosis in breast cancer cells [6], and the upregulated expression of NTSR1 is related to the tumor progression [7]
Summary
Neurotensin (NT) is a 13-amino acid regulatory peptide that was initially isolated from bovine hypothalamus by Carraway and Leeman [1] and was subsequently found to express highest in the small intestine [2]. The growthpromoting effect of NT/NTSR1 has been found in a variety of carcinomas including those of the colon, pancreas, prostate, and lung [4] It has been found in breast carcinomas that near all breast ductal carcinomas over express NTSR1 and about a third coexpress both NT (autocrine) and NTSR1 [5], NT exerted an inhibitory activity on the apoptosis in breast cancer cells [6], and the upregulated expression of NTSR1 is related to the tumor progression [7].
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